GLP-1 Levels Research Articles

Revisiting the markers interleukin-6 and glucagon-like peptide-1 for targeting low-grade inflammation in type 2 diabetes: a meta-analysis and our lab experience.

Type 2 diabetes (T2DM) manifests as pancreatic disorder as a consequence of low-grade systemic inflammation, attributed to upregulated levels of interleukin-6 (IL-6). This in turn is associated with a reduced incretin effect with lower circulatory GLP-1 levels. Therefore, its important to monitor the circulating IL-6 and GLP-1 levels for better management and outcomes in T2DM patients. Limited studies being available in literature on circulating concentrations of GLP-1 and IL-6 in T2DM patients, a meta-analysis was conducted by identifying 1558 studies from 3 databases. As per inclusion and exclusion criteria, the studies were screened for the 2-markers.Forest plots were drawn for standardized mean differences and median values were deduced from the datasets. In parallel, analysis was conducted to ascertain the expression levels of the markers by ELISA (n = 52 T2DM patients) in real time. The meta-analysis showed a significant (p < 0.01) standardized mean difference of 3.82 and 1.04 for IL-6 and GLP-1 respectively. The median values obtained from analysis for IL-6 were 26.50 pg/ml which were higher than the controls downregulated levels of GLP-1(8.77 pg/ml) were noted. The above findings are corroborated by the results of our experimental analysis with IL-6 concentrations at 11.603pg/ml and GLP-1 at 13.05pg/ml. The study highlights that systemic concentrations of IL-6 and GLP-1 correspond to a persistent low-grade inflammation and decreased incretin effect in T2DM patients which manifest as pancreatic β-cell dysfunction. The expression of the markers is inversely correlated and monitoring their levels is clinically important for targeting them through their potential antagonists thus reducing the risk of complications, thereby improving the quality of life of the patients.

Expression of PGC-1α, PPAR-α and UCP1 genes, metabolic and anthropometric factors in response to sodium butyrate supplementation in patients with obesity: a triple-blind, randomized placebo-controlled clinical trial.

There is increasing evidence that gut metabolites have a role in the etiology of obesity. This study aimed to investigate the effects of sodium butyrate (NaB) supplementation on the expression of peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1α (PGC-1α), PPAR-α, and uncoupling protein-1 (UCP-1) genes, as well as on the metabolic parameters and anthropometric indices in persons with obesity. In this triple-blind placebo-controlled randomized clinical trial, 50 individuals with obesity were randomly assigned to NaB (600 mg/day) + hypo-caloric diet or placebo group + hypo-caloric diet for 8 weeks. The study measured the participants' anthropometric characteristics, food consumption, and feelings of hunger in addition to the serum levels of metabolic indices and the mRNA expression of the PGC-1α, PPAR-α, and UCP-1 genes in peripheral blood mononuclear cells (PBMCs). PGC-1α and UCP-1 genes expression significantly increased in NaB group compared to the placebo at the endpoint. A significant decrease in weight, BMI, and waist circumference (WC) was observed in NaB group. Among the metabolic factors, NaB significantly decreased fasting blood sugar (FBS) (P = 0.04), low-density lipoprotein cholesterol (LDL-C) (P = 0.038) and increased high-density lipoprotein cholesterol (HDL-C) (P = 0.016). NaB could not significantly change serum GLP-1 level. This study unveiled NaB supplementation alone cannot have significant beneficial effects on anthropometric, and biochemical factors. NaB could affect anthropometric and metabolic risk variables associated with obesity only when prescribed, along with calorie restriction. This study was registered in the Iranian Registry of Clinical Trials ( https://en.irct.ir/trial/53968 ) on 31 January 2021 (registry number IRCT20190303042905N2).

The mitigating role of lysophospholipids in hepatic lipid metabolism and intestinal immunity in juvenile black seabream (Acanthopagrus schlegelii) fed a high-fat diet

An 8-week feeding experiment investigated the effects of lysophospholipids (LP) on growth performance, hepatic lipid metabolism, intestinal immunity and antioxidation in juvenile black seabream (Acanthopagrus schlegelii) (initial weight 4.60 ± 0.01 g) on a high-fat diet. Five experimental diets were established: normal fat diet (13 %, CON), high-fat diet (18 %, HFD) and HFD with different levels of LP (0.05 %, 0.1 %, and 0.2 %). The results indicated that dietary LP had no impact on the specific growth rate and survival rate of juvenile black seabream (P > 0.05), while 0.2 %LP supplementation reduced the intraperitoneal fat ratio (IPF) (P < 0.05). Dietary 0.1 % and 0.2 %LP supplementation reduced the total lipid content and the size and number of lipid droplets in the liver (P < 0.05). The diets supplemented with LP reduced the contents of TG and LDL-C in the serum (P < 0.05), without affecting T-CHO and HDL-C (P > 0.05). The expression of lipid transport genes including apoa, apob, fatp1, and fatp4, were markedly up-regulated with increased dietary LP supplementation (P < 0.05). Moreover, dietary 0.2 %LP supplementation notably increased mRNA expression levels of scarb1, ffar3, acsl5 and glp-1 in the intestine (P < 0.05). Dietary LP notably down-regulated the mRNA expression of genes related to the lipogenesis pathway including fas, aco and srebp-1c, while up-regulating mRNA expression of lipogenesis-related genes including cpt1α, lpl, and pparα (P < 0.05). Additionally, dietary 0.2 %LP supplementation notably increased total antioxidant capacity in the intestine and up-regulated expression levels of intestinal antioxidant genes, including mn sod, cu-zn sod, gpx, and cat (P < 0.05), fish fed diets with 0.2 %LP down-regulation of pro-inflammatory genes, including tnfα and nf-κb, and up-regulation of anti-inflammatory factors, tgfβ-1, il-10 and tight-junction protein genes including (oclna, cldni, cldn3, and tjp1b) in the intestine (P < 0.05). In conclusion, dietary LP improved intestinal fatty acid transport and liver lipolysis, alleviating intestinal oxidative damage and inflammatory reactions caused by HFD in black seabream.

12614 Induction Of Gpt2 During Metabolic Stress Is Associated With Reduced Incretin Responsiveness And Decreased β-cell Resilience To Metabolic Stress

Abstract Disclosure: S. Sen: None. A.V. Rozo: None. M. Haemmerle: None. J. Roman: None. A.V. Scota: None. J.A. Christine: None. E.M. Morrow: None. S.A. Tersey: None. C.B. Newgard: None. N.M. Doliba: None. D.A. Stoffers: None. Elevated blood glucose and lipids compromise pancreatic β-cell survival and function, but the underlying molecular mechanisms are ill-understood. We previously found that mitochondrial glutamate-pyruvate transaminase 2 (GPT2) is induced by ER and glucolipotoxic (GLT) stress. Here, we find that islets from type 2 diabetic donors exhibited markedly elevated levels of GPT2 compared to those of non-diabetic donors. GLT stress induced GPT2 in MIN6 cells, primary murine, and human non-diabetic islets. We generated β-cell specific Gpt2-deficient (Gpt2βKO) and Gpt2 floxed control (Gpt2f/f) mice to study the in vivo role of Gpt2 in β-cells. Intraperitoneal (IP) glucose tolerance (GTT) of Gpt2βKO mice was minimally affected on chow diet; therefore, we placed Gpt2f/f and Gpt2βKO mice on 45 kcal% high-fat and matched control diets. At 1 week, HFD-fed Gpt2βKO mice exhibited reduced β-cell death, measured by droplet digital PCR of circulating unmethylated preproinsulin DNA and by TUNEL analysis. Over 37 weeks, HFD-fed Gpt2βKO mice showed lower random blood glucose similar to Gpt2f/f mice under a control diet. While IPGTT was modestly improved in HFD-fed Gpt2βKO compared to HFD-fed Gpt2f/f mice, insulin secretion was not enhanced. Remarkably, oral glucose administration markedly improved glucose tolerance and enhanced insulin secretion of control- and HFD-fed Gpt2βKO mice compared to Gpt2f/f mice, while GLP-1 and GIP levels were unaltered, suggesting enhanced incretin action on the β-cell. Indeed, Gpt2βKO mice (under both control and high-fat diets) were more responsive to administration of GLP1R agonist Exendin-4 (Ex4) than Gpt2f/f mice. Isolated Gpt2βKO islets secreted more insulin when stimulated by Ex4 and GIP but not acetylcholine. Perifusion assay revealed markedly enhanced insulin secretion of Gpt2βKO islets in response to a stepwise exposure to increasing Ex4 doses, indicating enhanced incretin sensitivity. Metabolic flux analysis of Gpt2βKO and Gpt2f/f islets exposed to uniformly labeled glucose (U-13C glucose) under low (2.8mM), high (12mM) glucose, and high glucose with Ex4 conditions revealed elevated levels of key TCA cycle intermediates in Gpt2βKO islets under high glucose and high glucose+Ex4 conditions, indicating increased TCA cycle flux that likely enhances insulin secretion. Gpt2βKO mice had higher β cell mass than Gpt2f/f littermates under control diet and HFD feeding. Bulk islet RNA-seq from Gpt2f/f and Gpt2βKO mice exposed to GLT revealed upregulation of genes responsible for cell cycle and division pathways and downregulation of apoptosis and ER stress genes, consistent with enhanced survival of Gpt2βKO islets under stress conditions. In summary, β-cell GPT2 is increased during metabolic stress and T2D. Its deficiency induces a metabolic reprogramming that improves incretin sensitivity and protects pancreatic β-cells from metabolic stress. Presentation: 6/2/2024

7424 Measurements of Key Regulators of Energy Intake in Young and Midlife Women with Overweight or Obesity

Abstract Disclosure: E. Tama: None. R. Rivera: None. S. Fansa: None. D. Anazco: None. W. Ghusn: None. S. Faubion: None. A. Acosta: Consulting Fee; Self; Amgen Inc. Grant Recipient; Self; Vivus USA, Novo Nordisk. C. Shufelt: None. M.D. Hurtado: None. Introduction: Midlife women (ages 40 to 65) experience age-related weight gain (0.4-0.7 kg/year) due to physiologic and psychosocial changes. Evidence supports that age-related decrease in lean mass and its subsequent effect on energy expenditure are key physiologic factors. To date, the are no data describing if changes in the main regulators of energy intake (i.e., hunger, satiation, and satiety) across women’s lifespan play a role in weight gain during midlife. The aim of this study is to characterize measurements of satiation, satiety, and appetite sensations through early adulthood and midlife in women with obesity. Methods: This is a cross sectional study of women aged 19-65 with overweight or obesity who have undergone measurements of (i) body composition by DXA scan; (ii) resting energy expenditure (REE) by indirect calorimetry; (iii) satiation by calories consumed to satiation (CTS) during an ad libitum meal test; (iv) satiety by time needed to empty 50% of the stomach content (GEt1/2) in a gastric emptying study and plasma satiety hormone levels (PYY, GLP-1, and CCK); and (v) appetite sensations by visual analog scales (VAS) for hunger and fullness. We present data as mean ± standard deviation. We performed simple correlations between these variables and age. We performed multiple regression analyses to adjust for body composition and REE. Results: Our cohort included 552 mostly white (93%) women, with a mean age of 41±11 years and a mean BMI of 37±7 kg/m2. Increased age significantly correlated with higher waist circumference (r=0.1, p=0.006), waist/hip ratio (r=0.1, p=0.01), and total fat mass % (r=0.1, p=0.04); and with lower lean mass % (r=-0.1, p=0.04) and REE (r=-0.3, p&amp;lt;0.0001). Increased age was associated with decreased hunger sensation (i.e., lower preprandial VAShunger after an overnight fast, r=-0.1, p=0.04; and lower postprandial VAShunger 4hr after a standardized 320-kcal breakfast, r=-0.1, p=0.001), stronger satiation (i.e., lower CTS, r=-0.1, p=0.001), and more prolonged satiety (i.e., higher GEt1/2, r=0.1, p=0.02; higher postprandial GLP-1 levels, r=0.1, p=0.03; and higher postprandial VASfullness after and ad libitum meal, p=0.1, p=0.008). After adjusting for lean mass % and REE, the correlations between age and hunger sensations and satiation measurement, but not satiety measurements, were maintained. Conclusion: Our results show that older women have lower lean mass % and REE. After adjusting for these variables, older women experience decreased hunger sensation and achieve satiation with a lower number of calories. As these changes in theory would protect against midlife weight gain, the differences in body composition and REE remain the most likely culprit. Further research is necessary to investigate if there are other key factors that may contribute to weight gain such as the hedonic or emotional components of food intake. Presentation: 6/2/2024

Effects of Letrozole And Metformin Versus Metformin alone on incretin in Iraqi patients with PCOS

I Background: The emergence of numerous novel therapeutic agents for managing T2DM has expanded the assortment of tailored therapies available for PCOS sick. One illustration of these is the incretin-based therapeutic agents. Patients and methods:The extanttrainingcomprised 75 sickthrough an age extent of 18 to less than 40 years. Patients were categorized into three groups: metformin group (positive control group) and they received metformin as 500 mg per-oral (bid); letrozole group who were treated using 2.5 mg per-oral (bid), and combination groups who received both agents with similar doses as above. Each group included 25 females. Informationalmost age and body mass index (BMI) stayed included in the study. Serum measurement of incretin (GLP-1) was done before treatment and 90 days after treatment using Enzyme-Linked Immunosorbent Assay. Results: There stayed no importantvariance in mean age (p = 0.981) betweentraining groups and means of age were 29.24 ± 6.10 years, 29.56 ± 5.50 years and 29.44± 5.83 years, respectively and the range of age was between 18 and 40 years. In addition, in this training, there stayed no importantalteration in mean BMI (p = 0.534) among study groups and means of BMI were 28.80 ±2.72 kg/m2, 27.53 ±1.95 kg/m2 and 27.07 ±1.99 kg/m2, respectively and the range of BMI was between 21.07 and 31.18 kg/m2. Serum incretin (GLP-1) level showed no significant variation among study groups, the mean levels were in the range of 10.87 -13.79 ng/ml and the range of values was from 9.56 -14.49 ng/ml. Changes in BMI are shown in. Metformin alone caused in more important weight decrease; nevertheless, adding of letrozole caused significant reduction in body mass index, letrozole alone also affect body weight significantly. It was observed that combined use of either drug resulted in more significant change of GLP-1 level at (p ≤ 0.001). Conclusion: Combined treatment with letrozole and metformin is safe and efficient in femalesby PCOS resultant in weight decrease, improved insulin

Does GLP-1 cause post-bariatric hypoglycemia: ‘Computer says no’

Background and Objective:Patients who underwent Roux-en-Y Gastric Bypass surgery for treatment of obesity or diabetes can suffer from post-bariatric hypoglycemia (PBH). It has been assumed that PBH is caused by increased levels of the hormone GLP-1. In this research, we elucidate the role of GLP-1 in PBH with a physiology-based mathematical model. Methods:The Eindhoven Diabetes Simulator (EDES) model, simulating postprandial glucose homeostasis, was adapted to include the effect of GLP-1 on insulin secretion. Parameter sensitivity analysis was used to identify parameters that could cause PBH. Virtual patient models were created by defining sets of models parameters based on 63 participants from the HypoBaria study cohort, before and one year after bariatric surgery. Results:Simulations with the virtual patient models showed that glycemic excursions can be correctly simulated for the study population, despite heterogeneity in the glucose, insulin and GLP-1 data. Sensitivity analysis showed that GLP-1 stimulated insulin secretion alone was not able to cause PBH. Instead, analyses showed the increased transit speed of the ingested food resulted in quick and increased glucose absorption in the gut after surgery, which in turn induced postprandial glycemic dips. Furthermore, according to the model post-bariatric increased rate of glucose absorption in combination with different levels of insulin sensitivity can result in PBH. Conclusions:Our model findings implicate that if initial rapid improvement in insulin sensitivity after gastric bypass surgery is followed by a more gradual decrease in insulin sensitivity, this may result in the emergence of PBH after prolonged time (months to years after surgery).

Adropin Is Expressed in Pancreatic Islet Cells and Reduces Glucagon Release in Diabetes Mellitus.

Diabetes mellitus affects 537 million adults around the world. Adropin is expressed in different cell types. Our aim was to investigate the cellular localization in the endocrine pancreas and its effect on modulating pancreatic endocrine hormone release in streptozotocin (STZ)-induced diabetic rats. Adropin expression in the pancreas was investigated in normal and diabetic rats using immunohistochemistry and immunoelectron microscopy. Serum levels of insulin, glucagon pancreatic polypeptide (PP), and somatostatin were measured using a Luminex® χMAP (Magpix®) analyzer. Pancreatic endocrine hormone levels in INS-1 832/3 rat insulinoma cells, as well as pancreatic tissue fragments of normal and diabetic rats treated with different concentrations of adropin (10-6, 10-9, and 10-12 M), were measured using ELISA. Adropin was colocalized with cells producing either insulin, glucagon, or PP. Adropin treatment reduced the number of glucagon-secreting alpha cells and suppressed glucagon release from the pancreas. The serum levels of GLP-1 and amylin were significantly increased after treatment with adropin. Our study indicates a potential role of adropin in modulating glucagon secretion in animal models of diabetes mellitus.

Impact of a 12-Week Dietary Intervention on Adipose Tissue Metabolic Markers in Overweight Women of Reproductive Age.

The prevalence of overweight and obesity in women of reproductive age leads to significant health risks, including adverse metabolic and reproductive outcomes. Effective dietary interventions are critical to improving health outcomes in this population. This study investigates the impact of a 12-week diet intervention on metabolic markers of adipose tissue in overweight women of reproductive age, determining whether calorie restriction or low-starch diets are more effective, while also accounting for salivary amylase activity. A total of 67 overweight women of reproductive age were enrolled in a randomized controlled trial (RCT). Participants were divided into high-salivary-amylase (HSA) and low-salivary-amylase (LSA) groups based on baseline salivary amylase activity measured using a spectrophotometric method. Each group was further subdivided into two dietary intervention groups: calorie restriction (CR) and low starch (LS), resulting in four subgroups (HSA-CR, HSA-LS, LSA-CR, LSA-LS), along with a control group (CTR) of normal-weight individuals (no intervention). Participants were assigned to a calorie-restricted diet or a low-starch diet for 12 weeks. Key metabolic markers of adipose tissue, including insulin sensitivity, adipokines, cytokines, and lipid profiles, were measured at baseline (T0), 30 min after consuming starch-containing muesli (T1), and 12 weeks after intervention (T2). Active GLP-1, glucagon, and C-peptide levels were assessed to clarify the hormonal mechanisms underlying the dietary effects. Salivary amylase activity was also measured to examine its role in modulating glucose and GLP-1 responses. Both diet interventions led to significant improvements in metabolic markers of adipose tissue, though different ones. Calorie restriction improved insulin sensitivity by effectively reducing visceral fat mass and enhancing insulin signaling pathways. In contrast, the low-starch diet was linked to a reduction in the coefficient of glucose variation influenced partly by changes in GLP-1 levels. Our findings highlight the importance of personalized diet strategies to optimize metabolic health in this demographic.

Curcumin alone not combined with piperine exerts cardioprotective effects in pressure-overload rats by increasing glucagon-like peptide-1 receptor signaling and additional properties

Background and aimCurcumin has shown significant cardiovascular protective effects. However, the low bioavailability limits its practical application. As a natural bioenhancer, piperine is expected to increase the bioavailability of curcumin, and then, enhance its beneficial effects. Meanwhile, glucagon-like peptide-1 receptor (GLP-1R) signaling has been confirmed to be involved in the regulation of cardiovascular events. Herein, this study aimed to investigate whether piperine could enhance the beneficial effects of curcumin in pressure-overload rats and whether GLP-1/GLP-1R signaling is involved in their action mechanism. Methods and resultsMale Sprague-Dawley (SD) adult rats were subjected to abdominal aortic constriction (AAC) surgery to 16 weeks, which elevated blood pressure and induced cardiac hypertrophy. Curcumin (100 mg/kg/day) or/and piperine (20 mg/kg/day) were orally given for 4 weeks from the 17th week after AAC surgery. Curcumin alone treatment significantly lowered blood pressure, ameliorated cardiovascular remodeling, improved left ventricular performance and endothelium-dependent vascular relaxation. Accompanied by these results, GLP-1R expression in the myocardium was up-regulated. Piperine alone also exhibited a certain positive inotropic cardiac activity, but the effect was less significant. The combination of curcumin and piperine didn't show enhanced cardiovascular protective effects relative to curcumin, along with decreased fasting serum GLP-1 level and GLP-1R expression in the myocardium. ConclusionCurcumin exerts cardiovascular protective effects in pressure-overload rats by upregulating GLP-1R, and inhibiting of GLP-1/GLP-1R signaling pathway may be related to the limited beneficial effects of combination of curcumin and piperine. This study provides a new thinking that oral administration of some spices may affect cardiovascular function by modulating the GLP-1/GLP-1R system in a mode of gut-heart axis regulation.

Evaluating Serum Biomarkers (DPP-4, GLP-1, Ki-67 Protein) Levels for Early Detection of Diabetic Breast Cancer

Background: Breast tumours are the second most common cancer in women. A mammary cancer is a multi-step process that involves several cell types and is yet difficult to prevent globally. One of the best ways to prevent breast cancers is by early detection. In many affluent nations, the 5-year proportional perseverance ratio for people with mammary neoplasms is over 80% because to early detection. Over the past ten years, significant progress has been made in both the understanding of mammary tumours and the development of preventative interventions. Diabetes, often known as diabetes mellitus (DM), is a collection of illnesses characterized by elevated blood sugar levels brought on by flaws in the body's capacity to make and/or utilize insulin. Objectives: This study aimed to evaluate the levels of serum biomarkers (DPP-4, GLP-1, Ki-67 protein) in individuals with diabetes, breast cancer, diabetic breast cancer, and a control group. Methods: The samples were taken from individuals at Al-Najaf Teaching Hospital and the Najaf Cancer Centre between 30/10/2023 and 1/3/2024. The blood samples were 120 blood samples acquired from Iraqi subjects. The participants included four groups and each group consisted of 30 participants, (Diabetes type 2 patient group, Breast cancer patient group, Diabetic breast cancer patient group, and Control group). Results: The difference in serum DPP-4 levels, between diabetic, breast cancer individuals and healthy control groups, is statistically noteworthy. The results show a higher DPP-4 level in patient groups than in the control group. While there was no significance in the GLP-1 and Ki-67 proteins in the patient and control groups. Conclusion: These results suggest that high serum DPP-4 could serve as a useful screening marker for the early detection of diabetic breast cancer. ًWhile, The lack of differences in GLP-1 and Ki-67 proteins levels across the groups indicates these biomarkers may not be as informative for identifying diabetic breast cancer in this population.

Inhibition of somatostatin enhances the long-term metabolic outcomes of sleeve gastrectomy in mice

ObjectiveBariatric surgery is an effective treatment to obesity, leading to weight loss and improvement in glycemia, that is characterized by hypersecretion of gastrointestinal hormones. However, weight regain and relapse of hyperglycemia are not uncommon. We set to identify mechanisms that can enhance gastrointestinal hormonal secretion following surgery to sustain weight loss. MethodsWe investigated the effect of somatostatin (Sst) inhibition on the outcomes of bariatric surgery using a mouse model of sleeve gastrectomy (SG). ResultsSst knockout (sst-ko) mice fed with a calorie-rich diet gained weight normally and had a mild favorable metabolic phenotype compared to heterozygous sibling controls, including elevated plasma levels of GLP-1. Mathematical modeling of the feedback inhibition between Sst and GLP-1 showed that Sst exerts its maximal effect on GLP-1 under conditions of high hormonal stimulation, such as following SG. Obese sst-ko mice that underwent SG had higher levels of GLP-1 compared with heterozygous SG-operated controls. The SG-sst-ko mice regained less weight than controls and maintained lower glycemia months after surgery. Obese wild-type mice that underwent SG and were treated daily with a Sst receptor inhibitor for two months had higher GLP-1 levels, regained less weight, and improved metabolic profile compared to saline-treated SG-operated controls, and compared to inhibitor or saline-treated sham-operated obese mice. ConclusionsOur results suggest that inhibition of Sst signaling enhances the long-term favorable metabolic outcomes of bariatric surgery.

Ginseng extract improves pancreatic islet injury and promotes β-cell regeneration in T2DM mice.

Panax ginseng C. A. Mey. (Araliaceae; Ginseng Radix et Rhizoma), a traditional plant commonly utilized in Eastern Asia, has demonstrated efficacy in treating neuro-damaging diseases and diabetes mellitus. However, its precise roles and mechanism in alleviating type 2 diabetes mellitus (T2DM) need further study. The objective of this study is to explore the pharmacological effects of ginseng extract and elucidate its potential mechanisms in protecting islets and promoting β-cell regeneration. The T2DM mouse model was induced through streptozotocin combined with a high-fat diet. Two batches of mice were sacrificed on the 7th and 28th days following ginseng extract administration. Body weight, fasting blood glucose levels, and glucose tolerance were detected. Morphological changes in the pancreatic islets were examined via H & E staining. Levels of serum insulin, glucagon, GLP-1, and inflammatory factors were measured using ELISA. The ability of ginseng extract to promote pancreatic islet β-cell regeneration was evaluated through insulin & PCNA double immunofluorescence staining. Furthermore, the mechanism behind β-cells regeneration was explored through insulin & glucagon double immunofluorescence staining, accompanied by immunohistochemical staining and western blot analyses. The present research revealed that ginseng extract alleviates symptoms of T2DM in mice, including decreased blood glucose levels and improved glucose tolerance. Serum levels of insulin, GLP-1, and IL-10 increased following the administration of ginseng extract, while levels of glucagon, TNF-α, and IL-1β decreased. Ginseng extract preserved normal islet morphology, increased nascent β-cell population, and inhibited inflammatory infiltration within the islets, moreover, it decreased α-cell proportion while increasing β-cell proportion. Mechanistically, ginseng extract might inhibit ARX and MAFB expressions, increase MAFA level to aid in α-cell to β-cell transformation, and activate AKT-FOXM1/cyclin D2 to enhance β-cell proliferation. Our study suggests that ginseng extract may be a promising therapy in treating T2DM, especially in those with islet injury.

An endogenous GLP-1 circuit engages VTA GABA neurons to regulate mesolimbic dopamine neurons and attenuate cocaine seeking.

Recent studies show that systemic administration of a glucagon-like peptide-1 receptor (GLP-1R) agonist is sufficient to attenuate the reinstatement of cocaine-seeking behavior, an animal model of relapse. However, the neural mechanisms mediating these effects and the role of endogenous central GLP-1 signaling in cocaine seeking remain unknown. Here, we show that voluntary cocaine taking decreased plasma GLP-1 levels in rats and that chemogenetic activation of GLP-1-producing neurons in the nucleus tractus solitarius (NTS) that project to the ventral tegmental area (VTA) decreased cocaine reinstatement. Single nuclei transcriptomics and FISH studies revealed GLP-1Rs are expressed primarily on GABA neurons in the VTA. Using in vivo fiber photometry, we found that the efficacy of a systemic GLP-1R agonist to attenuate cocaine seeking was associated with increased activity of VTA GABA neurons and decreased activity of VTA dopamine neurons. Together, these findings suggest that targeting central GLP-1 circuits may be an effective strategy toward reducing cocaine relapse and highlight a novel functional role of GABAergic GLP-1R-expressing midbrain neurons in drug seeking.

Effects of Tryptophan Supplementation in Diets with Different Protein Levels on the Production Performance of Broilers.

Tryptophan plays an important role in the pig industry but has the potential to improve performance in the poultry industry. The purpose of this study was to examine the effects of tryptophan supplementation in diets with different protein levels on the feed intake, average daily gain (ADG), and feed conversion ratio (F/G) of broilers. A total of 180 twenty-one-day-old broilers (half male and half female) were weighed and randomly allocated to twelve groups, with six male and six female groups. Each group consisted of 15 broilers. The broilers were fed low- (17.2%), medium- (19.2%), or high- (21.2%) protein diets with or without extra tryptophan (up to 0.25%) during the 28-day experiment. Food intake and body weight were measured weekly during the trial period. Male broilers fed a medium-protein diet containing more tryptophan showed a lower F/G. In the low-protein diet groups, additional tryptophan caused a significant reduction in the feed intake of female broilers during the first two weeks. Moreover, the serum GLP-1, cholesterol, and bile acid levels, as well as the expression of FXR mRNA in the ileum, were significantly increased. Additionally, the FXR mRNA in the hypothalamus and the GCG and GLP-1R mRNAs in the ileum tended to increase in these broilers. In summary, the tryptophan concentration in the diet can influence the feed intake and metabolism of broilers. Under a standard diet, an appropriate amount of tryptophan is beneficial to the F/G of male broilers, while under a low-protein diet, tryptophan supplementation may cause a short-term reduction in the feed intake of female broilers by increasing serum GLP-1 and bile acid signals.

Efficacy of powder of ginsengporia and atractylodis macrocephalae combined with aerobic exercise in the treatment of obese T2DM: A randomized controlled clinical trial

BackgroundTo explore the efficacy of powder of ginsengporia and atractylodis macrocephalae combined with aerobic exercise in the treatment of obese T2DM and its influence on glucose and lipid metabolism indices. ResultsBoth groups of patients were given metformin drug treatment. The control group was given aerobic exercise intervention, and the observation group was given ginsengporia and atractylodis macrocephalae on the basis of the control group. The total effective rate of the observation group (95.74%) was higher than that of the control group (82.98%) (P < 0.05). After treatment, the main symptoms of the observation group were less (P < 0.05), such as thirst and lack of desire to drink, fatigue, loss of appetite, limb numbness and tingling, sticky stool, scanty dark urine, and lower total score. FPG, 2hPG, and HbA1c were lower (P < 0.05), FINS, HOMA-IR, and HOMA-β were higher (P < 0.05), TG, TC, and LDL-C were lower, and HDL-C levels were higher in the observation group (P < 0.05). After treatment, Nesfatin-1 and adiponectin were lower, visfatin and leptin were higher (P < 0.05), and GIP and GLP-1 levels were higher in the observation group (P < 0.05). No significant difference was found in the incidence of adverse reactions between the two groups (P > 0.05). ConclusionsPowder of ginsengporia and atractylodis macrocephalae combined with aerobic exercise is effective in treating obese T2DM, which can alleviate clinical symptoms and the disorder of glucose and lipid metabolism, and improve the islet function and gastrointestinal function.How to cite: Liu G, Kanti Das S. Efficacy of powder of ginsengporia and atractylodis macrocephalae combined with aerobic exercise in the treatment of obese T2DM: A randomized controlled clinical trial. Electron J Biotechnol 2024;71. https://doi.org/10.1016/j.ejbt.2024.04.006.

The health impact of substituting meat with plant-based meat alternatives: findings from a Systematic Review

Sales of plant-based meat alternatives (PBMAs) are increasing(1). While these products are becoming more popular, little is known about their impact on health(2). Therefore, the aim of this work was to systematically review the evidence on PBMA consumption and associated health outcomes.A wider systematic review looking at the environmental impact, ingredient composition, nutritional impact and health outcomes associated with PBMAs was conducted. A search strategy combined terms “meat alternatives” AND “environment” OR “ingredients” OR “nutrition” OR “health.” Five databases were searched, MEDLINE, EMBASE, Web of Science, Scopus and Greenfile, as well as reference lists of relevant articles. All study designs reporting primary data were included, except for animal studies and in vitro studies. Non-English studies and studies published before 2011 were excluded (PROSPERO Registration Number: CRD42021250541).2184 papers were identified, 1802 papers remained after duplicates were removed, 1536 were excluded at title and abstract screen stage, 266 full texts were assessed for eligibility and 54 papers were included in the analysis for all outcomes investigated. Ten studies examined the impact of PBMA vs. meat consumption on health outcomes. Three studies measured postprandial response to single test meals(3–5), four studies were longer-term RCTs(6–8) with two further separate publications reporting on different outcomes for the same RCT(9,10). One study was a prospective cohort(11) and one a cross-sectional study(12).Of the single test meal studies, no significant differences were observed for glucose levels in 2/2 studies (100%)(3,5), PYY and GLP-1 levels in 2/2 studies (100%)(3,4) and self-reported hunger/fullness in 3/3 studies (100%)(3–5). Significantly lower insulin concentrations and subsequent energy intakes were both reported in 1/2 studies (50%) following consumption of mycoprotein vs. chicken meals(3).Longer-term full and partial replacement of meat with PBMAs resulted in significantly lower body weight (kg) in 2/2 studies (100%)(6,10), significantly lower saturated fat intakes in 2/2 studies (100%) (6,10), significantly higher fibre intakes in 2/3 studies (67%)(6,7), improvements in plasma lipid profile in 2/3 studies (67%)(7,10) and positive changes in gut microbiota in 1/2 studies (50%)(8) compared to meat diet phases/control groups with no restrictions on meat intakes. There were no significant differences in protein intakes in 3/3 studies (100%)(6,7,10), energy, total fat and carbohydrate intakes in 2/2 studies (100%) (6,7), blood pressure in 2/2 studies (100%)(6,10), glucose levels in 2/2 studies (100%) (7,10) and insulin levels in 2/2 studies (100%)(7,10).No definitive conclusions can be made on the impact of PBMAs on health outcomes due to the small number of studies and variation in study designs, outcomes measured and the type of PBMA used. From the limited evidence available, no negative health effects from PBMA consumption were observed, however, further longer-term RCTs are needed to confirm this.

Circulating biomarker profile changes in obese patients undergoing bariatric surgery

Bariatric surgery (BS) remains the most effective treatment for morbid obesity (MO). It`s relevant to identify biomarkers for predicting the outcome of BS in patients with MO. The aim of the study was to determine the dynamical change in the biomarker levels in patients undergoing BS and apparently healthy donors. Serum and plasma samples were obtained from 66 patients, of which 26 patients with MO (aged 26–72 years) underwent BS, and 40 healthy donors, at the age of 56 ± 10.3 years. Patient samples were obtained the day before BS (first group), 3–7 months after BS (second group), and 7 or more months after BS (third group). Analyte concentrations were determined by multiplex immunoassay on the xMAP platform (Luminex). Spearman’s rank correlation was used. The nature of analyte variability was described by building multiple regression models. In the patients compared with healthy controls, differences in the levels of resistin, PAI1, MCP1, GLP1, leptin, FGF23, adiponectin, adipsin were observed. In patients after BS, the levels of resistin, ANGPTL6, FGF21, and leptin changed. In patients over 55 years old compared with younger patients, differences for total ANGPTL4, amylin, and pancreatic polypeptide were observed. Differences in levels of glucagon, resistin, GLP1 and leptin were noted between men and women. The dynamics of the levels of adipokines and incretins indicates biochemical changes in patients after BS compared with healthy persons.

Computational Screening for the Dipeptidyl Peptidase-IV Inhibitory Peptides from Putative Hemp Seed Hydrolyzed Peptidome as a Potential Antidiabetic Agent.

Dipeptidyl peptidase-IV (DPPIV) inhibitory peptides are a class of antihyperglycemic drugs used in the treatment of type 2 diabetes mellitus, a metabolic disorder resulting from reduced levels of the incretin hormone GLP-1. Given that DPPIV degrades incretin, a key regulator of blood sugar levels, various antidiabetic medications that inhibit DPPIV, such as vildagliptin, sitagliptin, and linagliptin, are employed. However, the potential side effects of these drugs remain a matter of debate. Therefore, we aimed to investigate food-derived peptides from Cannabis sativa (hemp) seeds. Our developed bioinformatics pipeline was used to identify the putative hydrolyzed peptidome of three highly abundant proteins: albumin, edestin, and vicilin. These proteins were subjected to in silico digestion by different proteases (trypsin, chymotrypsin, and pepsin) and then screened for DPPIV inhibitory peptides using IDPPIV-SCM. To assess potential adverse effects, several prediction tools, namely, TOXINpred, AllerCatPro, and HemoPred, were employed to evaluate toxicity, allergenicity, and hemolytic effects, respectively. COPID was used to determine the amino acid composition. Molecular docking was performed using GalaxyPepDock and HPEPDOCK, 3D visualizations were conducted using the UCSF Chimera program, and MD simulations were carried out with AMBER20 MD software. Based on the predictive outcomes, FNVDTE from edestin and EAQPST from vicilin emerged as promising candidates for DPPIV inhibitors. We anticipate that our findings may pave the way for the development of alternative DPPIV inhibitors.

Petroleum ether extract of Schisandra sphenanthera prevents hyperglycemia and insulin resistance in association with modulation of sweet taste receptors and gut microbiota in T2DM rats

Ethnopharmacological relevanceSchisandra sphenanthera (Schisandra sphenanthera Rehd. et Wils.) is the dried mature fruit of Schisandra sphenanthera, a plant in the Magnoliaceae family. It was used in the treatment of diabetes mellitus in the Jade Fluid Decoction and the Xiaoke pills, which were recorded in ancient books. However, its mechanism of action in the treatment of type 2 diabetes mellitus (T2DM) was unclear and needs further study. Aim of the studyThis research aimed to investigate the chemical composition and lignan content of Schisandra sphenanthera petroleum ether parts (SPEP) and to evaluate the effects of SPEP on sweet taste receptors (STRs) and intestinal flora in rats on a high-fat diet (HFD). Additionally, the relationships between SPEP and hyperglycemia and insulin resistance were examined. Materials and methodsGC-MS was used to determine the chemical composition of SPEP, and HPLC was used to determine the lignin content. A combination of the HFD and the administration of streptozotocin (STZ) was employed to generate a rat model of T2DM. Petroleum ether extracts from Schisandra sphenanthera were used as the focus of the research to evaluate the effects of these extracts on the glucolipid metabolism of T2DM rats, as well as the underlying mechanisms. ResultsAnalysis of the GC-MS spectrum of SESP revealed a total of 58 compounds. HPLC analysis revealed that SPEP had the highest concentration of Schisandrin A and the lowest concentration of Schisandrol A. The drug administration intervention resulted in a significant decrease in body weight and pancreatic weight of diabetic rats compared to the Normal group. When compared to the Model group, the body weight of rats in the drug administration group and the Metformin group had a more moderate decrease, while the pancreatic weight and pancreatic-to-body ratio increased. The Model group shown significant increases in FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, and NEFA, as well as significant decreases in HDL-C and SOD, when compared to the Normal group (P < 0.05). The administration of each group was found to be significantly effective in decreasing FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, NEFA, while increasing HDL-C and SOD when compared to the Model group. The application of SPEP had a positive impact on hepatocyte swelling, hepatocyte degeneration, and necrosis, as well as the morphological structure of pancreatic islet cells. Furthermore, the protein expression levels of T1R2, TRPM5 and GLP-1 in the small intestine of the Model group were reduced. After a period of six weeks, the protein expression levels began to align more closely with those of the Normal group of rats. Analysis of 16S rRNA sequencing revealed that the intestinal microbiota of diabetic rats was significantly disrupted, with a decrease in the abundance of the Firmicutes phylum and an increase in the abundance of the Bacteroidetes phylum. Furthermore, the composition of the dominant genus was distinct from that of the control group. After the drug intervention, the microbiota of diabetic rats was significantly altered, exhibiting a higher abundance and diversity, as well as a significant enrichment of the community. The SPEP treatment resulted in a significant increase in acetic acid, propionic acid, and butyric acid. ConclusionsThe findings of this research indicated that SPEP could be effective in treating T2DM through the regulation of STRs, the adjustment of disturbed metabolite levels, and the alteration of intestinal flora.