Reduced Fasting Blood Glucose Research Articles

Effect of <i>Vernonia amygdalina</i> and fish oil-supplemented biscuits on lipid profile parameters and blood glucose concentration of diabetic rats

Biscuit, a popular snack, serve as an ideal vehicle for incorporating therapeutic agents for disease management. This study aimed to assess the effect of Vernonia amygdalina (VO) and fish oil (FO)-supplemented biscuits (VFSB) on the total lipid profile and blood glucose concentration of diabetic rats. Forty-nine Wistar rats were allocated into seven groups (A to G). Upon induction and confirmation of diabetes in experimental rats, fasting blood glucose (FBG) level were monitored weekly using glucometer. Twenty-four hours after the last day of treatment, rats were sacrificed and serum total cholesterol (TC), triglyceride (TG), High-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) concentrations were assayed using assay kits. Results showed a significant (p < 0.05) reduction in FBG, TC, LDL-c, and TG concentrations in biscuit fed groups D, E, and F compared to group B fed VFSB. High-density lipoprotein cholesterol levels significantly increased (p < 0.05) in groups D, E, and F compared to Group B. In conclusion, Vernonia amygdalina and fish oil-supplemented biscuits exhibited a glucose-lowering effect and mitigated dyslipidemia associated with diabetes mellitus.

The loss of the hormonal function of bilirubin induces adiposity in male and female mice

The prevalence of obesity and its related comorbidities, including diabetes and metabolic dysfunction associated fatty liver disease (MAFLD), are on the rise globally, indicating the importance of new therapeutics for these diseases. Interestingly, serum bilirubin levels are negatively correlated with obesity, diabetes, and MAFLD. We have previously generated pegylated bilirubin nanoparticles (PEGBR) and demonstrated their therapeutic potential in the treatment of obesity and MAFLD. However, it’s unknown whether their beneficial effects are due to bilirubin’s antioxidant properties or its hormonal function by binding to and activating the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARa). To determine this, we used female and male hepatocyte-specific PPARa knockout mice ( PparaHepKO) and floxed ( Pparaflox) control mice on a high-fat diet for 30 weeks to induce adiposity and MAFLD. The mice were treated with vehicle or PEGBR (30 mg/kg) for six weeks. In female Pparaflox mice, PEGBR significantly lowered body weight, but not in the female PparaHepKO mice. A similar trend was seen in the male Pparaflox mice but was not statistically significant. PEGBR significantly reduced hepatic fat mass and triglycerides in the female and male Pparaflox mice but not in the PparaHepKO mice. Using lipidomics, we determined the lipid composition of the liver and how PEGBR changed it. In the male Pparaflox mice, PEGBR significantly reduced 109 lipid species, whereas, in the male PparaHepKO mice, PEGBR only reduced 7 species (93.6% reduction). In the female PparaHepKO mice, there was a 2.7% reduction in the number of lipid species significantly decreased by PEGBR compared to Pparaflox controls. Male Pparaflox mice had an increase in plasma high-density lipoprotein cholesterol and a decrease in very-low-density particle number with PEGBR, but this was not seen in the male PparaHepKO or female mice. In addition to protecting against the development of MAFLD, PEGBR significantly reduced fasting blood glucose and insulin levels only in the Pparaflox mice. Overall, the data indicates that the protective effects of bilirubin on obesity, MAFLD, and glucose tolerance are due to its hormonal function through PPARa. This study also confirms the therapeutic potential of bilirubin nanoparticles for obesity and its associated comorbidities. This work was supported by the National Institutes of Health F31HL170972 (Z.A.K.) and R01DK121797 (T.D.H.J.) and R01DA058933 (T.D.H.J.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Argyreia nervosa Mitigates Insulin Resistance in Liver via IR/IRS-1 Mediated Signaling in Streptozotocin-Induced Type-2 Diabetic Rats

Argyreia nervosa, commonly known as Hawaiian baby woodrose or wooly morning glory, is a plant native to India and is also found in various parts of the world. It is known for its seeds, which have been used traditionally in Ayurvedic and traditional medicine systems for various diseases. The study was aimed at assessing the effect of Argyreia nervosa on insulin signaling molecules of the liver in streptozotocin (STZ)-induced experimental type-2 diabetic rats. Healthy adult male Wistar albino rats -150-180 days old weighing 180-200g was used for the study and divided as Group I - Normal rats; Group II – type-2 diabetic rats; Group III -Diabetic rats + A. nervosa 500 mg/kg b.wt; Group IV-Normal rats + A. nervosa 500 mg/kg b.wt. Fasting blood glucose, and fasting serum insulin were measured by calorimetric methods. Further mRNA expression analysis of insulin receptor (IR) was measured in control and treated animals by quantitative Ream Time PCR analysis. A. nervosa root extract significantly reduced fasting blood glucose and serum insulin concentrations in STZ-induced rats compared with control. In addition, mRNA expression of IR showed a one-fold increase in the expression which shows that A. nervosa is involved in the regulation of insulin signaling in the liver and thereby reduces insulin resistance and type-2 diabetes. Our study concludes that A. nervosa root extract has a significant role on insulin signaling molecules thereby it reduces hyperglycemia and hyperinsulinemia via insulin receptor-mediated pathways. Hence, A. nervosa may be considered as one of the therapeutic natural antidiabetic drugs.

Osthole ameliorates early diabetic kidney damage by suppressing oxidative stress, inflammation and inhibiting TGF-β1/Smads signaling pathway

BackgroundOsthole is a natural active ingredient extracted from the traditional Chinese medicine Cnidium monnieri. It has been demonstrated to have anti-inflammatory, anti-fibrotic, and anti-hyperglycemic properties. However, its effect on diabetic kidney disease (DKD) remains uncertain. This study aims to assess the preventive and therapeutic effects of osthole on DKD and investigate its underlying mechanisms. MethodsA streptozotocin/high-fat and high-sucrose diet induced Type 2 diabetic rat model was established. Metformin served as the positive drug control. Diabetic rats were treated with metformin or three different doses of osthole for 8 weeks. Throughout the treatment period, the progression of DKD was assessed by monitoring increases in urinary protein, serum creatinine, urea nitrogen, and uric acid, along with scrutinizing kidney pathology. Enzyme-linked immunosorbent assay (ELISA) was employed to detect inflammatory factors and oxidative stress levels. At the same time, immunohistochemical staining was utilized to evaluate changes in alpha-smooth muscle actin, fibronectin, E-cadherin, and apoptosis. The alterations in TGF-β1/Smads signaling pathway were ascertained through western blot and immunofluorescence. Furthermore, we constructed a high glucose-stimulated HBZY-1 cells model to uncover its molecular protective mechanism. ResultsOsthole significantly reduced fasting blood glucose, insulin resistance, serum creatinine, uric acid, blood urea nitrogen, urinary protein excretion, and glomerular mesangial matrix deposition in diabetic rats. Additionally, significant improvements were observed in inflammation, oxidative stress, apoptosis, and fibrosis levels. The increase of ROS, apoptosis and hypertrophy in HBZY-1 cells induced by high glucose was reduced by osthole. Immunofluorescence and western blot results demonstrated that osthole down-regulated the TGF-β1/Smads signaling pathway and related protein expression. ConclusionOur findings indicate that osthole exhibits potential preventive and therapeutic effects on DKD. It deserves further investigation as a promising drug for preventing and treating DKD.

Effects of whole grains on glycemic control: a systematic review and dose-response meta-analysis of prospective cohort studies and randomized controlled trials

PurposeWhole grains have recently been promoted as beneficial to diabetes prevention. However, the evidence for the glycemic benefits of whole grains seems to conflict between the cohort studies and randomized control trials (RCTs). To fill the research gap, we conducted a meta-analysis to determine the effects of whole grains on diabetes prevention and to inform recommendations.MethodsWe searched PubMed, Clarivate Web of Science, and Cochrane Library until March 2024. We used the risk ratio (RR) of type 2 diabetes to represent the clinical outcomes for cohort studies, while the biomarkers, including fasting blood glucose and insulin, HbA1C, and HOMA-IR, were utilized to show outcomes for RCTs. Dose-response relationships between whole grain intakes and outcomes were tested with random effects meta-regression models and restricted cubic splines models. This study is registered with PROSPERO, CRD42021281639.ResultsTen prospective cohort studies and 37 RCTs were included. Cohort studies suggested a 50 g/day whole grain intake reduced the risk of type 2 diabetes (RR = 0.761, 95% CI: 0.700 to 0.828, I2 = 72.39%, P < 0.001) and indicated a monotonic inverse relationship between whole grains and type 2 diabetes rate. In RCTs, whole grains significantly reduced fasting blood glucose (Mean difference (MD) = -0.103 mmol/L, 95% CI: -0.178 to -0.028; I2 = 72.99%, P < 0.01) and had modest effects on HbA1C (MD = -0.662 mmol/mol (-0.06%), 95% CI: -1.335 to 0.010; I2 = 64.55%, P = 0.05) and HOMA-IR (MD = -0.164, 95% CI: -0.342 to 0.013; I2 = 33.38%, P = 0.07). The intake of whole grains and FBG, HbA1C, and HOMA-IR were significantly dose-dependent. The restricted spline curves remained flat up to 150 g/day and decreased afterward. Subgroup analysis showed that interventions with multiple whole-grain types were more effective than those with a single type.ConclusionOur study findings suggest that a daily intake of more than 150 g of whole grain ingredients is recommended as a population approach for diabetes prevention.

The efficacy and safety of GLP-1 receptor agonists in youth with type 2 diabetes: a meta-analysis

BackgroundGlucagon-like peptide 1 receptor agonists have been proven to be effective in adults with diabetes and children with obesity. However, children with type 2 diabetes constitute an underrepresented subpopulation with limited treatment options. This meta-analysis aimed to determine more precise estimates of the efficacy and safety of glucagon-like peptide-1 agonists in pediatric type 2 diabetes mellitus.MethodsThree databases were searched (PubMed, Embase, and Cochrane Central Register of Controlled Trials) for trials published until the end of March 2024. The search indexing terms included 3 categories: [1] type 2 diabetes mellitus [2], youth, and [3] glucagon-like peptide-1 receptor agonist (GLP-1 RA). Randomized controlled trials in youth with type 2 diabetes (age ≤ 18 years) that assessed anthropometric and metabolic parameters were included. A total of 1119 nonduplicate studies were retrieved, and 137 full-text articles were screened. The data were analyzed using mean differences (MDs) with 95% CIs and odds ratios (ORs) with 95% CIs. For outcomes with low heterogeneity, a fixed-effects model was used. Otherwise, we applied a random effects model. Our outcomes were Hb1Ac, fasting blood glucose (FBG), blood pressure, weight, and side effects.ResultsFive studies comprehending 415 children and adolescents were included. On average, GLP-1 RA reduced HbA1c levels (-1.01%; 95% CI, -1.26 to -0.76), fasting blood glucose levels (-1.88 mmol/L; 95% CI, -2.51 to -1.26), and body weight (-1.6 kg; 95% CI, -2.83 to -0.36). No significant reductions in systolic blood pressure (MD -0.19 mmHg; 95% CI, -3.9 to 3.52 mmHg) or diastolic blood pressure (MD 0.3 mmHg; 95% CI, -2.33 to 2.93 mmHg) were observed. Despite a higher incidence of side effects, withdrawal rates from the studies remained low.ConclusionsWithin this specific population, GLP-1 RAs exhibit a notable association with substantial reductions in HbA1c, FBG, and body weight. The administration of these medications is concurrent with an elevated incidence of side effects, which are predominantly gastrointestinal and tolerable.Trial registrationPROSPERO identifier: CRD42023393020.

A randomised double-blind placebo-controlled trial of a probiotic combination for manipulating the gut microbiota and managing metabolic syndrome

An increasing number of studies indicate that the occurrence of metabolic syndrome is significantly influenced by the host's gut microbiota and its metabolites. This study evaluated the potential application of a combination of Bifidobacterium adolescentis CCFM8630 and Lactobacillus reuteri CCFM8631 for the clinical remission of metabolic syndrome. This research comprised 40 individuals with metabolic syndrome, 21 of whom were in the probiotic intervention group and 19 in the placebo control group. The intervention duration was 11 weeks and involved the daily intake of 1 × 1010 CFU of a probiotic combination comprising Bifidobacterium adolescentis CCFM8630 and Lactobacillus reuteri CCFM8631. The serum biochemical indexes of the participants before and after the intervention were measured. After the intervention, faecal samples were collected to comprehensively analyse the gut microbiota of the participants by high-throughput sequencing and the faecal concentrations of target short-chain fatty acids by gas chromatography–mass spectrometry. The results showed that the 11-week probiotic intervention significantly reduced fasting blood glucose, fasting insulin, triglyceride, and low-density lipoprotein cholesterol concentrations in patients with metabolic syndrome and significantly increased the abundance of Bacteroidetes and some genera that produce short-chain fatty acids by regulating the abundance of gut microbial taxa that are strongly correlated with the clinical indicators of metabolic syndrome. These results demonstrated the beneficial effects of the probiotic combination on the clinical remission of metabolic syndrome, suggesting its potential application as an adjuvant strategy for the clinical treatment of metabolic syndrome in the future and laying a foundation for the further study of the mechanism of action of probiotics in alleviating metabolic syndrome.

Non-Pharmacological Interventions for Type 2 Diabetes in People Living with Severe Mental Illness: Results of a Systematic Review and Meta-Analysis.

People with serious mental illnesses (SMIs) such as schizophrenia and bipolar disorder die up to 30 years younger than individuals in the general population. Premature mortality among this population is often due to medical comorbidities, such as type 2 diabetes (T2D). Being a disease directly related to diet, adverse lifestyle choices, and side effects of psychotropic medication, an effective approach to T2D treatment and management could be non-pharmacological interventions. This systematic review and meta-analysis (1) summarise the current evidence base for non-pharmacological interventions (NPI) for diabetes management in people living with SMI and (2) evaluate the effect of these interventions on diverse health outcomes for people with SMI and comorbid diabetes. Six databases were searched to identify relevant studies: PubMed (MEDLINE), PsycINFO, Embase, Scopus, CINAHL, and Web of Science. Studies were included if they reported on non-pharmacological interventions targeted at the management of T2D in people living with SMI. To be eligible, studies had to further involve a control group or report multiple time points of data in the same study population. Whenever there were enough interventions reporting data on the same outcome, we also performed a meta-analysis. Of 1867 records identified, 14 studies were included in the systematic review and 6 were also eligible for meta-analysis. The results showed that there was a reduction, although not significant, in glycated haemoglobin (HbA1c) in the NPI group compared with the control, with a mean difference of -0.14 (95% CI, -0.42, 0.14, p = 0.33). Furthermore, NPI did not significantly reduce fasting blood glucose in these participants, with a mean difference of -17.70 (95% CI, -53.77, 18.37, p = 0.34). However, the meta-analysis showed a significant reduction in psychiatric symptoms: BPRS score, -3.66 (95% CI, -6.8, -0.47, p = 0.02) and MADRS score, -2.63 (95% CI, -5.24, -0.02, p = 0.05). NPI also showed a significant reduction in the level of total cholesterol compared with the control, with a mean difference of -26.10 (95% CI, -46.54, -5.66, p = 0.01), and in low-density lipoprotein (LDL) cholesterol compared with control, with a standardised mean difference of -0.47 (95% CI, -0.90, -0.04, p = 0.03). NPI did not appear to have significant effect (p > 0.05) on body mass index (BMI), health-related quality of life (HRQL), triglycerides, and high-density lipoprotein cholesterol compared with control. This systematic review and meta-analysis demonstrated that NPI significantly (p < 0.05) reduced psychiatric symptoms, levels of total cholesterol, and LDL cholesterol in people with type 2 diabetes and SMI. While non-pharmacological interventions also reduced HbA1c, triglyceride, and BMI levels and improved quality of life in these people, the effects were not significant (p > 0.05).

1H-NMR-based metabolomics reveals the preventive effect of Enteromorpha prolifera polysaccharides on diabetes in Zucker diabetic fatty rats.

The primary objective of this investigation was to explore the beneficial impacts of Enteromorpha prolifera polysaccharide (EP) on dysglycemia in Zucker diabetic fatty (ZDF) rats, while also shedding light on its potential mechanism using 1H-NMR-based metabolomics. The results demonstrated a noteworthy reduction in fasting blood glucose (FBG, 46.3%), fasting insulin (50.17%), glycosylated hemoglobin A1c (HbA1c, 44.1%), and homeostatic model assessment of insulin resistance (HOMA-IR, 59.75%) following EP administration, while the insulin sensitivity index (ISI, 19.6%) and homeostatic model assessment of β-cell function (HOMA-β, 2.5-fold) were significantly increased. These findings indicate that EP enhances β-cell function, increases insulin sensitivity, and improves insulin resistance caused by diabetes. Moreover, EP significantly reduced serum lipid levels, suggesting improvement of dyslipidemia. Through the analysis of serum metabolomics, 17 metabolites were found to be altered in diabetic rats, 14 of which were upregulated and 3 of which were downregulated. Notably, the administration of EP successfully reversed the abnormal levels of 9 out of the 17 metabolites. Pathway analysis further revealed that EP treatment partially restored metabolic dysfunction, with notable effects observed in valine, leucine, and isoleucine metabolism; aminoacyl-transfer RNA (tRNA) biosynthesis; and ketone body metabolism. These findings collectively indicate the potential therapeutic efficacy of EP in preventing glycemic abnormalities and improving insulin resistance. Thus, EP holds promise as a valuable treatment option for individuals with diabetes.

Puerarin alleviates diabetic nephropathy by inhibiting Caspase-1-mediated pyroptosis.

Diabetic nephropathy (DN) is an important cause of end-stage renal disease, with podocyte injury as the main feature. Pyroptosis plays a non-negligible role in the process of diabetic nephropathy. Puerarin (PR) treatment of diabetic nephropathy has great potential, but the mechanism is not very clear. This article aims to study the protective effect and mechanism of puerarin on DN. Streptozotocin (STZ)-induced C57 BL/6J mouse model of DN was given PR, Necrosulfomide (NSA), Nigericin for 12 weeks; A 60 mM high glucose(HG) induced MPC5 cell injury model was administered to PR, NSA, and Nigericin interventions for 24 h. After 12 weeks of administration, PR reduced fasting blood glucose levels in DN mice, alleviated glomerular lesions, reduced podocyte damage, and protected renal function. Meanwhile, PR also inhibits the expression of pyroptosis-related proteins. In addition, PR alleviated the release of Interleukin 18 (IL-18), Interleukin 1beta (IL-1β), and lactate dehydrogenase (LDH) in MPC5 cells under HG conditions, downregulated the expression of pyrozozois-related proteins, and improved Caspase-1-mediated pyroptosis in MPC5 cells. Our study suggests that the beneficial effects of PR in diabetic nephropathy may be associated with inhibition of Caspase-1-mediated pyroptosis.

Extract of Gardenia jasminoides Ellis Attenuates High-Fat Diet-Induced Glycolipid Metabolism Disorder in Rats by Targeting Gut Microbiota and TLR4/Myd88/NF-κB Pathway.

Gardenia jasminoides Ellis is abundant in crocin and has a longstanding historical usage both as a dietary and natural ethnic medicine. Enhanced studies have increasingly revealed the intricate interplay between glycolipid metabolism and gut microbiota, wherein their imbalance is regarded as a pivotal indicator of metabolic disorders. Currently, the precise molecular mechanism of the crude extract of crocin from Gardenia jasminoides Ellis (GC) targeting gut microbiota to regulate glycolipid metabolism disorder is still unclear. Firstly, we explored the effect of GC on digestive enzymes (α-amylase and α-glucosidase) in vitro. Secondly, we investigated the effect of GC on the physical and chemical parameters of high-fat diet (HFD) rats, such as body weight change, fasting blood glucose and lipid levels, and liver oxidative stress and injury. Then, 16S rDNA sequencing was used to analyze the effects of GC on the composition and structure of gut microbiota. Finally, the impact of GC on the TLR4/Myd88/NF-κB signaling pathway in the intestine was assessed by Western Blotting. In the present study, GC was found to exhibit a hypoglycemic effect in vitro, by inhibition of digestive enzymes. In animal experiments, we observed that GC significantly reduced fasting blood glucose, TC, and TG levels while increasing HDL-C levels. Additionally, GC demonstrated hepatoprotective properties by enhancing liver antioxidative capacity through the upregulation of SOD, CAT, and GSH-Px, while reducing ROS. 16S rDNA sequencing results showed that GC had a significant effect on the gut microbiota of HFD rats, mainly by reducing the ratio of Firmicutes/Bateroidota, and significantly affected the genera related to glycolipid metabolism, such as Akkermansia, Ligilactobacillus, Lactobacillus, Bacteroides, Prevotellaceae, etc. The Western Blotting results demonstrated that GC effectively downregulated the protein expressions of TLR4, Myd88, and NF-κB in the intestine of HFD rats, indicating that GC could target the TLR4/Myd88/NF-κB pathway to interfere with glycolipid metabolism disorder. Correlation analysis revealed that GC could target the Akkermansia-TLR4/Myd88/NF-κB pathway axis which attenuates glycolipid metabolism disorder. Therefore, this study establishes the foundation for GC as a novel therapeutic agent for glycolipid metabolism disorder chemoprevention, and it introduces a novel methodology for harnessing the potential of natural botanical extracts in the prevention and treatment of metabolic syndrome.

KOMBINASI KACANG MERAH DAN KULIT KACANG HITAM PADA TIKUS WISTAR MODEL DIABETES MELITUS TIPE 2

Type 2 Diabetes Mellitus (T2DM) is a metabolic disease that require pharmacological and non-pharmacological therapies. Comsuming functional foods that are high in antioxidants and fiber such as red beans and black beans beneficial to patients with T2DM. The study aimed to examine the effect of the combination of red beans (Phaseolus vulgaris L.) flour and black beans (Phaseolus vulgaris) coat extract on body weight, blood glucose, insulin level and pancreatic tissue of T2DM model rats. This randomized controlled trial involved 36 male Wistar rats divided into 6 groups consisted of non-diabetic rats (Group I) and nicotinamide-streptozotocin induced diabetic rats (Group II-VI). Group II was negative control; Group III-V were given a combination with the proportion of flavonoid/ fiber in each kgBW as follows: 22.5 mg/0.25 g; 45 mg/0.5 g; and 90 mg/1 g. Group VI was the positive control. Data on body weight, fasting blood glucose levels and insulin levels were analyzed using Two-Way Anova, while pancreatic histopathology scoring data used Kruskal-Wallis.There was a significant difference between the dose and duration of intervention on body weight, fasting blood glucose and insulin levels (p=0.001). The intervention groups showed there were no pancreatic histopathology change as good as the positive control (p&gt;0.05). The combination of flavonoids and fiber at a dose of 45 mg/0.5 g per kgBW was proven to gain weight, reduce fasting blood glucose levels, increase insulin levels and no pancreatic histopathology change in T2DM rats models as well as the postive control group.

Assessment of anti-hyperglycemic and anti-hyperlipidemic effects of thiazolidine-2,4-dione derivatives in HFD-STZ diabetic animal model

Type 2 diabetes mellitus (T2DM) is a chronic endocrine/metabolic disorder characterized by elevated postprandial and fasting glycemic levels that result in disturbances in primary metabolism. In this study, we evaluated the metabolic effects of thiazolidine-2,4-dione derivatives in Wistar rats and Swiss mice that were fed a high-fat diet (HFD) for 4 weeks and received 90 mg/kg of streptozotocin (STZ) intraperitoneally as a T2DM model. The HFD consisted of 17% carbohydrate, 58% fat, and 25% protein, as a percentage of total kcal. The thiazolidine-2,4-dione derivatives treatments reduced fasting blood glucose (FBG) levels by an average of 23.98%–50.84%, which were also improved during the oral starch tolerance test (OSTT). Treatment with thiazolidine-2,4-dione derivatives also improved triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and total cholesterol levels (P < 0.05). The treatment intake has also shown a significant effect to modulate the altered hepatic and renal biomarkers. Further treatment with thiazolidine-2,4-dione derivatives for 28 days significantly ameliorated changes in appearance and metabolic risk factors, including favorable changes in histopathology of the liver, kidney, and pancreas compared with the HFD/STZ-treated group, suggesting its potential role in the management of diabetes. Thiazolidine-2,4-dione derivatives are a class of drugs that act as insulin sensitizers by activating peroxisome proliferator-activated receptor-gamma (PPAR-γ), a nuclear receptor that regulates glucose and lipid metabolism. The results of this study suggest that thiazolidine-2,4-dione derivatives may be a promising treatment option for T2DM by improving glycemic control, lipid metabolism, and renal and hepatic function.

Effects of DPP4 Inhibitors as Neuroprotective Drug on Cognitive Impairment in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis and Systematic Review.

Type 2 diabetes mellitus is considered as one of the risk factors for cognitive impairment. DPP4 inhibitors are effective drugs for the treatment of type 2 diabetes mellitus. However, the relationship between DPP4 inhibitors and cognitive dysfunction remains unclear. Therefore, we used a meta-analysis to determine the association between DPP4 inhibitors and cognitive impairment in type 2 diabetes mellitus. We systematically searched PubMed, CNKI, and the Cochrane Library at the time of establishment, 2022, and then made inclusion criteria and screened strategies to identify studies with more precise correlations. We included 10 studies with 5,583 participants. The data showed that DPP4 inhibitors significantly reduced the incidence rate of cognitive impairment in type 2 diabetes mellitus (SMD: 0.99; 95% CI [0.59, 1.38]). Furthermore, there was a linear correlation found between cognitive impairment in type 2 diabetes mellitus and fasting blood glucose, 2-hour postprandial blood glucose, and glycosylated hemoglobin. DPP4 inhibitors decreased fasting blood glucose (FPG) (SMD: 0.52; 95% CI [-0.68, -0.37]), blood glucose (2hPPG) at 2 hours after the meal (SMD: 0.82; 95% CI, [-1.2, -0.43]), and HbA1c (SMD: 0.34; 95% CI [-0.48, -0.21]). All data were statistically significant (P < 0.0001). Furthermore, we conducted subgroup analyses of the following measures at various treatment durations and ages: cognitive scores, fasting blood glucose, glycosylated hemoglobin, and two-hour postprandial blood glucose. DPP4 inhibitors significantly improved type 2 diabetic mellitus individuals' cognitive impairment and reduced fasting blood glucose, 2-hour postprandial blood glucose, and glycosylated hemoglobin. Subgroup analysis showed that people aged 60 to 70 years had better treatment effects at 0-180 days. This trial is registered with CRD42023399473.

Natural Sweetener Glycyrrhetinic Acid Monoglucuronide Improves Glucose Homeostasis in Healthy Mice.

Noncaloric or low-caloric sweeteners have become popular worldwide, although debates persist regarding their impact on health. To investigate whether the sweeteners are favorable for glucose homeostasis, our study assessed the effects of glycyrrhetinic acid monoglucuronide (GAMG) and several commonly used sweeteners [glycyrrhetinic acid (GA), stevioside, erythritol, sucralose, and aspartame] on glycometabolism and elucidated the underlying mechanisms. The C57BL/6J male mice were exposed to different sweeteners for 10 weeks, and our results showed that GAMG significantly reduced fasting blood glucose (FBG) levels (FBG-control: 3.81 ± 0.42 mmol/L; FBG-GAMG: 3.37 ± 0.38 mmol/L; p < 0.05) and the blood glucose levels 15 and 30 min after sucrose or maltose loading (p < 0.05). Furthermore, it improved glucose tolerance (p = 0.028) and enhanced insulin sensitivity (p = 0.044), while the other sweeteners had negligible or adverse effects on glucose homeostasis. Subsequent experiments showed that GAMG inhibited α-glucosidases potently (IC50 = 0.879 mg·mL-1), increased three SCFA-producing bacteria and SCFAs levels (p < 0.05), and promoted the gene expression of SCFA receptor GPR43 (p = 0.018). These results suggest that GAMG may regulate blood glucose by inhibiting α-glucosidases and modulating gut microbial SCFAs. Our findings prove that GAMG, beneficial to blood glucose regulation, is a promising natural sweetener for future utilization.

Does Quinoa (Chenopodium quinoa) Consumption Improve Blood Glucose, Body Weight and Body Mass Index? A Systematic Review and Dose-Response Meta-Analysis of Clinical Trials.

Quinoa (Chenopodium quinoa) has a structure similar to whole grains and contains phytochemicals and dietary fiber. Hence, it is considered a food substance with a high nutritional value. The purpose of the present study was to assess the efficacy of quinoa in reducing fasting blood glucose (FBG), body weight (BW), and body mass index (BMI) in a meta-analysis of randomized clinical trials. A comprehensive search in ISI Web of Science, Scopus, and PubMed databases as well as Google Scholar, was conducted up to November 2022 to identify reports of randomized clinical trials that investigated the effect of quinoa on FBG, BW, and BMI. Seven trials comprising 258 adults with mean ages of 31 to 64 years were included in this review. Studies used 15 to 50 grams of quinoa/per day as an intervention, and the intervention was between 28 to 180 days. In a dose-response analysis of FBG, there was significant evidence of a nonlinear association between intervention and FBG based on the quadratic model (P-value for nonlinearity = 0.027); hence, the slope of the curve increased when quinoa intake was nearly 25 g/- day. In comparison between quinoa seed supplementation and placebo, our findings showed that quinoa seed supplementation did not have a significant effect on BMI (MD: -0.25; 95% CI: -0.98, 0.47; I2=0%, P = 0.998) and BW (MD: -0.54; 95% CI: -3.05, 1.97; I2=0%, P = 0.99), when compared with placebo. Evidence of publication bias was not found among the included studies. The present analysis revealed the beneficial effects of quinoa on the blood glucose level. Further studies on quinoa are needed to confirm these results.

S-9-PAHSA's neuroprotective effect mediated by CAIII suppresses apoptosis and oxidative stress in a mouse model of type 2 diabetes.

With the rapidly increasing prevalence of metabolic diseases such as type 2 diabetes mellitus (T2DM), neuronal complications associated with these diseases have resulted in significant burdens on healthcare systems. Meanwhile, effective therapies have remained insufficient. A novel fatty acid called S-9-PAHSA has been reported to provide metabolic benefits in T2DM by regulating glucose metabolism. However, whether S-9-PAHSA has a neuroprotective effect in mouse models of T2DM remains unclear. This invivo study in mice fed a high-fat diet (HFD) for 5 months used fasting blood glucose, glucose tolerance, and insulin tolerance tests to examine the effect of S-9-PAHSA on glucose metabolism. The Morris water maze test was also used to assess the impact of S-9-PAHSA on cognition in the mice, while the neuroprotective effect of S-9-PAHSA was evaluated by measuring the expression of proteins related to apoptosis and oxidative stress. In addition, an invitro study in PC12 cells assessed apoptosis, oxidative stress, and mitochondrial membrane potential with or without CAIII knockdown to determine the role of CAIII in the neuroprotective effect of S-9-PAHSA. S-9-PAHSA reduced fasting blood glucose levels significantly, increased insulin sensitivity in the HFD mice and also suppressed apoptosis and oxidative stress in the cortex of the mice and PC12 cells in a diabetic setting. By suppressing oxidative stress and apoptosis, S-9-PAHSA protected both neuronal cells and microvascular endothelial cells in invivo and invitro diabetic environments. Interestingly, this protective effect of S-9-PAHSA was reduced significantly when CAIII was knocked down in the PC12 cells, suggesting that CAIII has a major role in the neuroprotective effect of S-9-PAHSA. However, overexpression of CAIII did not significantly enhance the protective effect of S-9-PAHSA. S-9-PAHSA mediated by CAIII has the potential to exert a neuroprotective effect by suppressing apoptosis and oxidative stress in neuronal cells exposed to diabetic conditions. Furthermore, S-9-PAHSA has the capability to reduce fasting blood glucose and LDL levels and enhance insulin sensitivity in mice fed with HFD.

Artesunate improves glucose and lipid metabolism in db/db mice by regulating the metabolic profile and the MAPK/PI3K/Akt signalling pathway

BackgroundDiabetes is a metabolic disorder characterized by chronic hyperglycaemia. Chronic metabolic abnormalities and long-term hyperglycaemia may result in a wide range of acute and chronic consequences. Previous studies have demonstrated that artesunate(ART) has antidiabetic, anti-inflammatory, antiatherosclerotic, and other beneficial effects, but the specific regulatory mechanism is not completely clear. AimThis study investigated the effects of ART on metabolic disorders in type 2 diabetes mellitus (T2DM) model db/db mice and explored the underlying mechanisms involved. MethodsC57BL/KsJ-db/db mice were used to identify the targets and molecular mechanism of ART. Metabolomic methods were used to evaluate the efficacy of ART in improving T2DM-related metabolic disorders. Network pharmacology and transcriptomic sequencing were used to analyse the targets and pathways of ART in T2DM. Finally, molecular biology experiments were performed to verify the key targets and pathways selected by network pharmacology and transcriptomic analyses. ResultsAfter a 7-week ART intervention (160 mg/kg), the glucose and lipid metabolism levels of the db/db mice improved. Additionally, the oxidative stress indices, namely, the MDA and SOD levels, significantly improved (p<0.01). Linoleic acid and glycerophospholipid metabolism, amino acid metabolism, bile acid synthesis, and purine metabolism disorders in db/db mice were partially corrected after ART treatment. Network pharmacology analysis identified important targets of ART for the treatment of metabolic disorders in T2DM . These targets are involved in key signalling pathways, including the highest scores observed for the PI3K/Akt signalling pathway. Transcriptomic analysis revealed that ART could activate the MAPK signalling pathway and two key gene targets, HGK and GADD45. Immunoblotting revealed that ART increases p-PI3K, p-AKT, Glut2, and IRS1 protein expression and suppresses the phosphorylation of p38, ERK1/2, and JNK, returning HGK and GADD45 to their preartesunate levels. ConclusionTreatment of db/db mice with 160 mg/kg ART for 7 weeks significantly reduced fasting blood glucose and lipid levels. It also improved metabolic imbalances in amino acids, lipids, purines, and bile acids, thereby improving metabolic disorders. These effects are achieved by activating the PI3K/AKT pathway and inhibiting the MAPK pathway, thus demonstrating the efficacy of the drug.

Comparison of the anti-diabetic effects of various grain and legume extracts in high-fat diet and streptozotocin-nicotinamide-induced diabetic rats

The anti-diabetic properties of whole groats and dietary fibers from various grains and legumes are well known. Nevertheless, studies on the anti-diabetic effects of their extracts are limited, and it is difficult to compare their efficacy. This study investigated the anti-diabetic potential of ethanol extracts from oats (OE), sorghum (SE), foxtail millet (FE), proso millet (PE), adzuki bean (AE), and black soybean (BE) in a high-fat diet and streptozotocin-nicotinamide-induced diabetic rat models. The extracts, obtained using 99.9 % ethanol, were orally administered to diabetic rats for four weeks. Various parameters were evaluated, including fasting blood glucose levels, glucose tolerance, insulin sensitivity, serum insulin levels, and pancreas histological analysis. OE and SE effectively reduced fasting blood glucose levels and the area under the curve (AUC) in the oral glucose tolerance test. Only OE significantly decreased the AUC in the insulin tolerance test and increased insulin concentration and homeostatic model assessment of the β-cell function index, indicating improved insulin sensitivity and β-cell function. Histological and immunohistochemical analysis of the pancreas supported these findings, demonstrating that OE protected against pancreatic cell damage. In contrast, FE, PE, AE, and BE did not have a significant effect on diabetes-related parameters. These findings identify OE as the most promising natural intervention for diabetes management.

Unraveling the superiority of (−)‐gallocatechin gallate to (−)‐epigallocatechin‐3‐gallate in protection of diabetic nephropathy of db/db mice

AbstractGCG ((−)‐gallocatechin gallate) and EGCG ((−)‐epigallocatechin‐3‐gallate) are main biologically active polyphenolic compounds in tea leaves, and EGCG has been studied for its potential effects on alleviating diabetic nephropathy (DN). Previous studies showed that GCG exhibited better hypoglycemic and antioxidant efficacy than EGCG. However, the efficacy and molecular mechanisms of GCG in the protection of DN are unknown. In this study, db/db mice were administered with EGCG or GCG orally for 20 weeks to comparatively investigate their effects on DN. These results revealed that GCG was significantly more effective than EGCG in decreasing water intake and urine excretion, reducing fasting blood glucose levels and systolic blood pressure, improving mesenteric artery contractility, enhancing the right renal hemodynamics, and improving key renal function markers. Through transcriptome analysis, S100A8/S100A9, two regulators of interstitial fibrosis, were identified and found to be more sensitive to GCG intervention, which was further confirmed by mRNA and protein expression data. In addition, the molecular docking analysis results demonstrated that GCG displayed a superior binding affinity toward S100A8/S100A9 in comparison to EGCG. Overall, our study found that GCG holds significant potential for the treatment of DN and outperforms EGCG in terms of efficacy.