Insulin Levels Research Articles

Therapeutic Potential of Thunbergia laurifolia L. Extract in Gestational Diabetes Mellitus: Insights from a Rat Model.

To assess the effects of Thunbergia laurifolia L. extract (TLE) on gestational diabetes mellitus (GDM) in a rat model. Thunbergia laurifolin L. leaves were subjected to ethanolic extraction. In vivo study, 50 pregnant rats were randomly divided into 5 groups (10 for each): non-GDM group, GDM induced by streptozotocin (STZ, 60 mg/kg i.p.), metformin (MET) 100 mg/kg, TLE 50, and 500 mg/kg groups. Administration was performed on gestation day 7 until term (day 21). The effects of TLE on blood glucose, insulin levels, lipid profiles, liver enzymes, and maternal performances were assessed. In in vitro study, the effect of TLE was examined using the organ bath for uterine force measurement. In in vivo study, TLE significantly reduced blood glucose as compared to GDM (P<0.05) with gradually increased insulin level. This effect was consistent with islets of Langerhans restoration. Histologically, the uterine muscular layer displayed a marked increase in fiber area in response to both doses as compared to GDM (P<0.05). Additionally, TLE significantly reduced total cholesterol, triglyceride, and alanine transaminase levels (P<0.05). Intriguingly, TLE also led to a notable augmentation in gravid uterus size, live fetuses count, and implantation numbers, while significantly reducing the post-implantation loss rate associated with fetal classification (P<0.05). Thus, GDM improvements were close to those produced by MET. In in vitro study, TLE exerted a concentration-dependent inhibition of spontaneous uterine contractility (half-maximal inhibition concentration=1.2 mg/L). This inhibitory effect extended to potassium chloride depolarization and oxytocin-mediated contractions. When combined with its major constituent, rosmarinic acid, TLE produced an enhanced inhibitory effect (P<0.05). TLE ameliorated blood glucose levels, enhanced uterine muscular structure, and improved maternal and fetal performance in GDM. TLE also displayed tocolytic properties. These findings underscore the need for further exploration of TLE as a potential tocolytic agent to mitigate GDM-associated complications.

GTPBP8 mitigates nonalcoholic steatohepatitis (NASH) by depressing hepatic oxidative stress and mitochondrial dysfunction via PGC-1α signaling

Nonalcoholic steatohepatitis (NASH) is emerging as a major cause of liver transplantation and hepatocellular carcinoma (HCC). Regrettably, its pathological mechanisms are still not fully comprehended. GTP-binding protein 8 (GTPBP8), belonging to the GTP-binding protein superfamily, assumes a crucial role in RNA metabolism, cell proliferation, differentiation, and signal transduction. Its aberrant expression is associated with oxidative stress and mitochondrial dysfunctions. Nevertheless, its specific functions and mechanisms of action, particularly in NASH, remain elusive. In our current study, we initially discovered that human hepatocytes L02 displayed evident mitochondrial respiratory anomaly, mitochondrial damage, and dysfunction upon treatment with palmitic acids and oleic acids (PO), accompanied by significantly reduced GTPBP8 expression levels through RNA-Seq, RT-qPCR, western blotting, and immunofluorescence assays. We then demonstrated that GTPBP8 overexpression mediated by adenovirus vector (Ad-GTPBP8) markedly attenuate lipid accumulation, inflammatory response, and mitochondrial impair and dysfunction in hepatocytes stimulated by PO. Conversely, adenovirus vector-mediated GTPBP8 knockdown (Ad-shGTPBP8) significantly accelerated lipid deposition, inflammation and mitochondrial damage in PO-treated hepatocytes in vitro. Furthermore, we constructed an in vivo NASH murine model by giving a 16-week high fat high cholesterol diet (HFHC) diet to hepatocyte specific GTPBP8-knockout (GTPBP8HKO) mice. We firstly found that HFHC feeding led to metabolic disorder in mice, including high body weight, blood glucose and insulin levels, and liver dysfunctions, which were accelerated in these NASH mice with GTPBP8 deficiency in hepatocytes. Consistently, GTPBP8HKO remarkably exacerbated the progression of NASH phenotypes induced by HFHC, as proved by the anabatic lipid accumulation, inflammation, fibrosis and reactive oxygen species (ROS) production in liver tissues, which could be largely attributed to the severe mitochondrial damage and dysfunction. Mechanistically, we further identified that GTPBP8 interacted with peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in hepatocytes. Importantly, the hepaprotective effects of GTPBP8 against mitochondrial dysfunction, oxidative stress and inflammation was largely dependent on PGC-1α expression. Collectively, GTPBP8 may exert a protective role in the progression of NASH, and targeting the GTPBP8/PGC-1α axis may represent a potential strategy for NASH treatment by improving mitochondrial functions.

The Physical Home Food Environment in Relation to Children’s Diet Quality and Cardiometabolic Health

BackgroundHome food availability has been identified as an important influence on dietary intake. Less is known about the relationship between the physical home food environment (HFE) and factors of cardiometabolic health in children. ObjectiveThe purpose of this study was to explore the relationship between the physical HFE and diet quality and factors of cardiometabolic health (eg, weight and blood biomarkers). DesignThis was a cross-sectional secondary analysis with 1 or more children per household. Participants/settingThis study included 44 children aged 6 to 12 years from 29 households in the Newark, DE area between August 2020 and August 2021. Main outcome measuresThe Home Food Inventory provides an obesogenic score (ie, score indicative of the presence of energy-dense foods) for the overall HFE and HFE subcategories scores; body mass index z-scores were calculated using measured height and weight; diet quality was measured using the Healthy Eating Index 2020 (HEI-2020) total scores; and cardiometabolic biomarkers were obtained from serum blood samples. Statistical analyses performedUnadjusted and adjusted linear mixed model regressions were used to test the association between the physical HFE and each of the outcome variables: body mass index z scores, HEI-2020 total scores, and cardiometabolic biomarkers. HFE subcategories (eg, fruits and vegetables) were also examined with each outcome using linear mixed model regression. ResultsMean ± SD age of the children was 9.5 ± 1.9 years, 61.4% were female, 59.1% identified as White, and 90.9% were non-Hispanic. Obesogenic score was significantly associated with body mass index z scores (β = .03, P = .029), but not HEI-2020 total scores or cardiometabolic biomarkers. As HFE fruits and vegetables subcategory increased, HEI-2020 total scores significantly increased (β = .73, P = .005) and total cholesterol (β = –1.54, P = .014) and low-density lipoprotein cholesterol levels (β = –1.31, P = .010) significantly decreased. Increased availability of sweet and salty snack food and availability of sugar-sweetened beverages was associated with increased fasting blood glucose (β = 0.65, P = .033) and insulin levels (β = 5.60, P = .035) respectively. ConclusionsThere is evidence of a relationship between the subcategories of the physical HFE and cardiometabolic factors. Future interventions are needed to understand whether altering the overall HFE or specific subcategories within the HFE can improve cardiometabolic health.

Comparison of Serum Vitamin D Levels in Obese Subjects with and without Type 2 Diabetes Mellitus.

Although observational studies have reported a correlation between vitamin D deficiency and type 2 diabetes mellitus (T2DM), epidemiological evidence on the risk of obese subjects suffering T2DM due to a vitamin D deficiency is limited. Therefore, we investigated the correlation between T2DM and serum vitamin D, lipids, blood pressure, insulin indexes in an obese population. A total of 1440 participants including 450 healthy controls and 990 obese subjects, 470 without T2DM and 520 with T2DM. Serum vitamin D levels were measured, and the association between low levels and T2DM in obese subjects was examined using multinomial and linear regression analyses. Of the participants, 35% had deficient or insufficient vitamin D levels (ie, <20 ng/mL). Compared with healthy controls, obese subjects, particularly those with T2DM had lower vitamin D levels. Multinomial logistic regression analysis showed that obese subjects with T2DM had a gradually increasing risk for desirable (RO = 1.41, 95% CI 1.06-1.93, P = 0.027), insufficient (RO = 1.83, 95% CI 1.27-2.84, P < 0.001), or deficient ((RO = 2.14, 95% CI 1.15-3.75, P = 0.014) vitamin D levels. In obese subjects with T2DM, vitamin D levels correlated inversely with the risk indicators for diabetes, such as the levels of HbA1c (β = -0.16, P = 0.002), fasting insulin (Fins; β = -0.31, P = 0.008), and HOMA-IR (β = -0.19, P < 0.001). In obese subjects without T2DM, vitamin D was associated negatively with the risk of having T2DM at five-year follow-up (relative risk = 0.93, 95% CI 0.79-0.97, P = 0.037). This study demonstrates that low vitamin D levels correlate with the presence of T2DM in the obese population. This finding indicates that hypovitaminosis D may be a potential biological vulnerability factor for the development of T2DM in obese subjects.

Protective effect and mechanism of Zuogui Jiangtang Jieyu Formula on damage to hippocampal synaptic microenvironment in rats with diabetes-related depression based on microglia-neuron crosstalk signal CD300f/TLR4

This study aims to reveal the protective effect and mechanism of Zuogui Jiangtang Jieyu Formula on the damage to hippo-campal synaptic microenvironment in rats with diabetes-related depression(DD) via regulating microglia immune receptor molecule-like family member f(CD300f)/Toll-like receptor 4(TLR4) signal. Firstly, the model of DD rats was established by a two-week high-fat diet+STZ injection+chronic mild and unpredictable stress plus isolation for 28 days. The rats were randomly divided into normal group, model group, CD300f blocker(CLM1, 2 μg·kg~(-1)) group, CD300f agonist(Fcγ, 5 μg·kg~(-1)) group, positive drug(0.18 g·kg~(-1) metformin+1.8 mg·kg~(-1) fluoxetine) group, and high-dose and low-dose(20.52 and 10.26 g·kg~(-1)) Zuogui Jiangtang Jieyu Formula groups. Depression-like behavior of rats was evaluated by open field and forced swimming experiments. The levels of blood glucose and insulin were detected by biochemical analysis. The levels of tumor necrosis factor α(TNF-α), interleukin-1β(IL-1β), indoleamine 2, 3-dioxygenase(IDO), 5-hydroxytryptamine(5-HT), and dopamine(DA) in the hippocampus were detected by enzyme-linked immunosorbent assay. The changes in the synaptic ultrastructure in hippocampal neurons of rats were observed by transmission electron microscopy. The protein expressions of CD300f, TLR4, synaptophysin(SYN), and postsynaptic density protein 95(PSD-95) in microglial cells of the hippocampus were detected by immunofluorescence and Western blot. The results indicated that compared with that in the normal group, the total movement distance in open field experiments was reduced in the model group, and the immobility time in forced swimming experiments increased, with an elevated insulin level in serum, as well as TNF-α, IL-1β, and IDO levels in the hippocampus. The 5-HT and DA levels in the hippocampus were reduced. In addition, the CD300f expression was down-regulated in microglial cells of the hippocampus, and the TLR4 expression was up-regulated. Moreover, the expression of synapse-related proteins SYN and PSD-95 in hippocampal neurons decreased, and the synaptic ultrastructure of hippocampal neurons was significantly damaged. Compared with the model group, the CD300f blocker and agonist aggravated and alleviated the above abnormal changes, respectively. High-dose and low-dose Zuogui Jiangtang Jieyu Formula could significantly improve the above depression-like beha-vior in rats, inhibit the abnormal increase of TNF-α, IL-1β, and IDO and the decrease of 5-HT and DA, effectively increase the expression of CD300f in microglial cells, and decrease the expression of TLR4. They could up-regulate the protein expression of presyna-ptic membrane SYN and postsynaptic membrane PSD-95 in hippocampal neurons and finally improve the damage to the hippocampal synaptic microenvironment. In conclusion, this research confirmed that Zuogui Jiangtang Jieyu Formula effectively alleviated the depression-like behavior and inhibited inflammatory activation of microglial cells in the hippocampus of rats with DD, and the mechanism might be related to the regulation of CD300f/TLR4 signal to alleviate the damage to hippocampal synaptic microenvironment.

Imeglimin enhances glucagon secretion through an indirect mechanism and improves fatty liver in high-fat, high-sucrose diet-fed mice.

Imeglimin is a recently approved oral antidiabetic agent that improves insulin resistance, and promotes insulin secretion from pancreatic β-cells. Here, we investigated the effects of imeglimin on glucagon secretion from pancreatic α-cells. Experiments were carried out in high-fat, high-sucrose diet-fed mice. The effects of imeglimin were examined using insulin and glucose tolerance tests, glucose clamp studies, and measurements of glucagon secretion from isolated islets. Glucagon was measured using both the standard and the sequential protocol of Mercodia sandwich enzyme-linked immunosorbent assay; the latter eliminates cross-reactivities with other proglucagon-derived peptides. Plasma glucagon, insulin and glucagon-like peptide-1 levels were increased by imeglimin administration in high-fat, high-sucrose diet-fed mice. Glucose clamp experiments showed that the glucagon increase was not caused by reduced blood glucose levels. After both single and long-term administration of imeglimin, glucagon secretions were significantly enhanced during glucose tolerance tests. Milder enhancement was observed when using the sequential protocol. Long-term administration of imeglimin did not alter α-cell mass. Intraperitoneal imeglimin administration did not affect glucagon secretion, despite significantly decreased blood glucose levels. Imeglimin did not enhance glucagon secretion from isolated islets. Imeglimin administration improved fatty liver by suppressing de novo lipogenesis through decreasing sterol regulatory element binding protein-1c and carbohydrate response element binding protein and their target genes, while enhancing fatty acid oxidation through increasing carnitine palmitoyltransferase I. Overall, the present results showed that imeglimin enhances glucagon secretion through an indirect mechanism. Our findings also showed that glucagon secretion promoted by imeglimin could contribute to improvement of fatty liver through suppressing de novo lipogenesis and enhancing fatty acid oxidation.

Sex- and age-associated factors drive the pathophysiology of MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with obesity. Sex and age affect MASLD prevalence and pathophysiology. The use of animal models fed Western-style diets is vital for investigating the molecular mechanisms contributing to metabolic dysregulation and for facilitating novel drug target identification. However, the sex-associated and age-associated mechanisms underlying the pathophysiology remain poorly understood. This knowledge gap limits the development of personalized sex-specific and age-specific drug treatments. Young (7wk) and aged (52wk) male and female mice were fed a high-fat diet (HFD) or low-fat diet. Liver metabolome (>600 molecules) and transcriptome profiles were analyzed. Male and female mice fed an HFD developed obesity, glucose intolerance, and hepatic steatosis. However, fasting blood glucose, insulin, and serum alanine aminotransferase levels were higher in males fed an HFD, indicating a more severe metabolic disease. In addition, males showed significant increases in liver diacylglycerides and glycosylceramides (known mediators of insulin resistance and fibrosis), and more changes in the transcriptome: extracellular matrix organization and proinflammatory genes were elevated only in males. In contrast, no major increase in damaging lipid classes was observed in females fed an HFD. However, aging affected the liver to a greater extent in females. Acylcarnitine levels were significantly reduced, suggestive of changes in fatty acid oxidation, and broad changes in the transcriptome were observed, including reduced oxidative stress response gene expression and alterations in lipid partitioning genes. Here, we show distinct responses to an HFD between males and females. Our study underscores the need for using both sexes in drug target identification studies, and characterizing the molecular mechanisms contributing to the MASLD pathophysiology in aging animals.

Effect and Predictive Value of Blood HbA1c, FBG, 2hPBG, and FINS on the Pregnancy Outcome in Patients with Gestational Diabetes Mellitus.

This study aimed to investigate the effects of hemoglobin A1c (HbA1c), fasting blood glucose (FBG), 2-hours postprandial blood glucose (2hPBG), and fasting insulin (FINS) levels on pregnancy outcomes and their predictive value in patients with gestational diabetes mellitus (GDM). A total of 109 pregnant women with GDM (GDM group) were included and assayed for serum FBG, 2hPBG, HbA1c, and FINS levels. The incidence of adverse pregnancy outcomes was recorded. GDM patients were divided into the poor pregnancy outcome group and the favorable pregnancy outcome group and analyzed for HbA1c, FBG, 2hPBG, and FINS. The predictive value of serum index combined detection on GDM pregnancy outcome was assessed, and the effect of serum indices on pregnancy outcome was evaluated in GDM patients with logistic regression. In the GDM group, there were 8 cases of premature membranes breaking (7.34%), 6 cases of premature delivery (5.50%), 3 cases of hyperamniotic fluid (2.75%), 2 cases of neonatal asphyxia (1.83%), 5 cases of fetal growth restriction (4.59%), and 3 cases of low-birth-weight infants (2.75%). The total incidence of adverse preg-nancy outcomes was 24.77% (27/109). HbA1c, FBG, 2hPBG, and FINS in the poor pregnancy outcome group were higher than those in the favorable pregnancy outcome group. The AUC value of blood biochemical indicators combined detection in predicting pregnancy outcome in GDM patients was higher than of HbA1c, FBG, 2hPBG, and FINS alone detection. HbA1c ≥ 6.94%, FBG ≥ 7.18 mmol/L, 2hPBG ≥ 9.36 mmol/L, and FINS ≥ 13.07 U/L were the risk factors affecting pregnancy outcomes in GDM patients. The changes of HbA1c, FBG, 2hPBG, and FINS levels in GDM patients are associated with adverse pregnancy outcomes, and the combined detection of serum indicators has predictive value for pregnancy outcomes in GDM patients.

Murine nuclear tyrosyl-tRNA synthetase deficiency leads to fat storage deficiency and hearing loss

Aminoacyl-tRNA synthetases are fundamental to the translation machinery with emerging roles in transcriptional regulation. Previous cellular studies have demonstrated tyrosyl-tRNA synthetase (YARS1 or TyrRS) as a stress response protein through its cytosol-nucleus translocation to maintain cellular homeostasis. Here, we established a mouse model with a disrupted TyrRS nuclear localization signal, revealing its systemic impact on metabolism. Nuclear TyrRS deficiency (YarsΔNLS) led to reduced lean mass, reflecting a mild developmental defect, and reduced fat mass, possibly due to increased energy expenditure. Consistently, YarsΔNLS mice exhibit improved insulin sensitivity and reduced insulin levels, yet maintain normoglycemia, indicative of enhanced insulin action. Notably, YarsΔNLS mice also develop progressive hearing loss. These findings underscore the crucial function of nuclear TyrRS in the maintenance of fat storage and hearing and suggest that aminoacyl-tRNA synthetases' regulatory roles can affect metabolic pathways and tissue-specific health. This work broadens our understanding of how protein synthesis interconnects metabolic regulation to ensure energy efficiency.

Early senescence of pancreatic β cells induced by unfolded protein response deficiency prevents type 1 diabetes.

Type 1 diabetes (T1D) is a T lymphocyte-mediated autoimmune disease caused by pancreatic β‍-cell destruction, which eventually leads to reduced insulin level and increased blood glucose level (Syed, 2022). As a multifactorial disease, T1D is characterized by a genetic predisposition associated with various environmental and cellular elements (Syed, 2022). Pancreatic β cells have long been considered the "innocent victims" in T1D pathogenesis since the pancreas is attacked by the immune cells, resulting in a process known as insulitis, in which the immune cells infiltrate pancreatic islets and secrete pro-inflammatory cytokines. However, growing evidence suggests that various β‍-cell stresses, dysfunction, and death contribute to T1D pathogenesis, as it has been observed that β‍-cell dysfunction in autoantibody-positive (Aab+) individuals exists long before T1D diagnosis (Evans-Molina et al., 2018).

Dietary oxygenated water mitigates type 2 diabetes mellitus by modulating gut microbiota and enhancing glucose metabolism in skeletal muscle

Type 2 diabetes mellitus (T2DM) is a significant health concern resulting from dysregulation of glucose metabolism, emphasizing the need for effective dietary interventions. Emerging evidence suggests a correlation between diabetes and hypoxia, indicating that oxygenated water (ORW) may hold promise in mitigating T2DM. This study employed a multifaceted approach involving physiological, genomic, metabolomic, transcriptomic, and molecular biological analyses to investigate the effects of ORW on T2DM and its underlying mechanisms. The results demonstrated that ORW effectively ameliorated key symptoms of T2DM by improving polydipsia and polyphagia, reducing fasting blood glucose, enhancing glucose tolerance, and increasing insulin levels. Notably, the beneficial effects of ORW appeared to be mediated through modulation of gut-muscle interactions by influencing gut microbiota composition and metabolite profiles. Transcriptomic and molecular analyses revealed that ORW activated the Akt signaling pathway and upregulated key genes involved in glucose uptake and utilization in skeletal muscle, as evidenced by increased p-AKT/AKT ratio and upregulation of Irs1, Glut4, Hk2, and Pfk. Collectively, these findings demonstrate that ORW alleviates T2DM by modulating gut microbiota while enhancing glucose uptake/utilization in skeletal muscle, supporting its potential use as an effective adjuvant strategy for targeted regulation of T2DM.

Potential hepato-protective effect of Salvia hispanica (chia) and Chenopodium quinoa (quinoa) in diabetic male albino rats

Chia and quinoa seeds are novel sources of bioactive compounds that may improve lipid profile, blood glucose homeostasis, and body weight in diabetic rats. This work aims to study the effect of different percentages of chia and quinoa consumption, alone or in a mixture, compared to Metformin drug on regulating lipid profile, blood glucose level, and weight of male diabetic rats. The consumption of quinoa and chia seeds showed a significant decline in fasting blood glucose (FBG), fasting insulin level, Hemoglobin A1C (HbA1c), and Homeostatic Model Assessment for Insulin (HOMA-IR), while the best results were obtained with Metformin and chia seeds. A decrease in mean body weight, triglycerides, total cholesterol, low density lipoprotein (LDL-C), and very low-density lipoprotein (VLDL-C), and an increase in high density lipoprotein (HDL-C) occurred, which was significant when consuming chia and quinoa seeds rather than treatment with metformin. Chia and quinoa seeds could improve blood glucose homeostasis and lipid profile in diabetic rats. These research findings could promote the daily consumption of quinoa and chia as great functional foods that could improve blood glucose homeostasis and lipid profile.

Whole-genome resequencing and RNA-seq analysis implicates GPR75 as a potential genetic basis related to retarded growth in South China carp (Cyprinus carpio rubrofuscus)

The south China carp (Cyprinus carpio rubrofuscus) is an indigenous and important fish species, widely cultured in south China. However, part of individuals experienced retarded growth, the genetic basis of which has yet to be elucidated. In this study, whole-genome resequencing of 35 fast-growing and 35 retarded-growing south China carp were conducted to identify promising genes associated with retarded growth. Twelve candidate SNPs were detected and annotated to the Gpr75 gene, which has been reported to be related with body weight through regulating insulin homeostasis. RNA-seq analysis of muscle suggested that differentially expressed genes were significantly enriched in the insulin signaling pathway. Additionally, the fasting serum insulin level was significantly lower while the blood glucose level was significantly higher in the retarded-growing group. Our preliminary study provides insights into the genetic basis underlying the retarded growth and may facilitate further genetic improvement of south China carp.

High-fat diet impact on prostate gland from adiponectin knockout mice: Morphometric, metabolic and inflammatory cytokines analyses

AimsObesity is a global public health issue, and some studies have linked it to an increased risk of prostatic diseases. This study aimed to evaluate the effects of a high-fat diet on metabolic parameters and prostate morphology in wild-type (WT) and adiponectin knockout (KO) mice. Main methodsMale WT and KO mice were fed a control diet (CD) or high-fat diet (HFD) for 6 months. Serum metabolic parameters, inflammatory cytokines in epididymal fat tissue, dorsal prostatic lobe morphometry and histopathology were analyzed. Key findingsCD WT and CD KO mice did not exhibit altered metabolic or prostatic parameters. However, HFD WT mice showed altered glucose and insulin tolerance even without excessive weight gain. On the other hand, HFD KO mice developed obesity, with an increase in low-density lipoprotein (11.8 ± 5.1 vs. 31.4 ± 3.6 mg/dL), high-density lipoprotein (73.4 ± 7.4 vs. 103.4 ± 2.5 mg/dL), and total cholesterol levels (126.2 ± 16.1 vs. 294.6 ± 23.2 mg/dL), a decrease in insulin levels (28.7 ± 12.2 vs. 4.6 ± 2.3 μIU/mL), and glucose and insulin resistance. We also observed that HFD KO animals display an increase in inflammatory cytokines, such as IL6, IL1β, and IL1RA. The dorsal prostate from HFD KO animals also presented significant increases in the mast cells (1.9 ± 0,7 vs. 5,3 ± 1.5 cells/field) and Ki67 index (2.91 ± 0.6 vs. 4.7 ± 0.4 %). SignificanceThe above findings highlight the complex interactions between adiponectin, metabolism, malnutrition, and prostate health. Metabolic deregulation combined with adipose inflammation potentially induces a proliferative and inflammatory microenvironment in the prostate gland under conditions of low adiponectin production, potentially impairing prostate morphophysiology in the context of obesity and aging.

Hypoglycemic effects of organic extracts from Ganoderma sp. and Kombucha in streptozotocin-induced diabetic Wistar rats

Evaluate the hypoglycemic effects of Kombucha and Ganoderma aqueous extractsin a model of diabetes with streptozotocin. Eight-week-ol male wistar ratsweighimg approximately 180 g were randomized into four groups (12 rats eachgroup). Control group (C), streptozotocin (E) without treatment, Kombucha (K)was given Kombucha extract 324 mg/kg orally, and Ganoderma group (G) wasgiven 250 mg/kg orally both for 45 days. Four animals per group were sacrificedat 2-, 15- and 45-days post treatment. Consumption of water and food wereregistered. Blood glucose and insulin levels were measured by spectrophotometryand the islets of Langerhans in the pancreas were quantified by ELISA assay. Datawere analyzed with an ANOVA two-ways and Tukey’s test as post hoc, Sigmastat3.1 Software was used and 0.05% significance was considered. Among the mainresults found, both extracts presented hypoglycemic effects after 15 days oftreatment. An interaction between the number of islets, insulin synthesis, water,and food consumption were also found with the streptozotocin group thatpresented the lowest average number of islets compared to other groups. Bothextracts showed a hypoglycemic, protective and regenerative effect on thepancreas, with differences observed in the physical condition of the animalstreated with Ganoderma, which showed signs of cachexia.

Nano-cubosomes of the phyto-active principle in Withania somnifera: LC-MS-NMR, anti-microbial, and insights of the anti-neuropathic and anti-inflammatory mechanism

Withania somnifera (W. somnifera) has a long history of safety in the amelioration of neuro-active ailments. The current study aims to explore Withania somnifera phyto-active principle anti-microbial, ant-neuropathic, and anti-inflammatory activities, and to modify these activities utilizing nano-cubosomes exploiting their mechanisms of action. Bio-guided fractionation technique was utilized, to identify the most phyto-active compound, using LC-MS-NMR online technique and biological models of diabetes, neuropathy, and inflammation. In-vitro antibacterial activity was also monitored. The HbA1c, in-vivo antioxidant (serum-catalase, TBARS, and GSH), serum insulin, and pro-inflammatory serum cytokines (TNF alpha, IL-six, and IL-ten) levels have been assessed to establish the anti-neuropathic and anti-inflammatory mechanisms. The nano-cubosomal formulations (CUB 1–3) were utilized to improve the W. somnifera most active compound efficacy. W. somnifera has shown ten major peaks; coagulin Q (10.2 %), dihydrowithanolide A (2.4 %), dihydrowithaferin D (1.8 %), physagulin D (7.6 %), withanoside V (2.3 %), withanolide A (WDA, 10.3 %), withafrin A (4.9 %), withaferin D (7.7 %), withanone 9 (9.9 %), withanolide D (4.8 %). The bio-guided fractionation technique utilizing LC-MS-NMR technique has proved that withanolide A (WDA) is the most phyto-active compound in W. somnifera. The latter has shown better results than WDA, which might be due to other effective compounds in Ws. However, CUB 3 (WDA nano-cubosomes dispersion) has shown more prominent anti-diabetic, anti-neuropathic, anti-inflammatory, and anti-bacterial potentials than Ws and WDA. Thus, CUB 3 modified WDA activity, and improved its efficacy. The normalization of HbA1c levels, increased insulin secretagogue potential, and the amelioration of the oxidative-stress may be the underlying Ws, WDA, and CUB 3 antidiabetic neuropathy mechanism. Moreover, the Ws, WDA, and CUB 1–3 anti-inflammatory mechanism might be due to the amelioration of the pro-inflammatory serum cytokines (decreasing TNF alpha and IL-six levels and increasing IL-ten). Thus, CUB 3 might be a powerful tool in augmenting Withania somnifera activity as an oral drug-delivery system and improving its efficacy against neuropathy and inflammation.

Intermittent fasting-induced improving insulin resistance in healthy obese adults

Background: Obesity is a severe global public health problem linked to chronic noncommunicable disease and increased mortality. It has harmful effects on metabolic disorders via the insulin resistance pathway. Available guidelines recommend caloric reduction via intermittent fasting for obesity management. However, the available literature is less focused on the benefits of intermittent fasting on improved insulin resistance in healthy obese adults, especially related to an accumulation of free fatty acids. Therefore, a scoping review is necessary. Objective: This review aims to collect evidence on the benefits of intermittent fasting on improved insulin resistance in healthy obese adults. Methods: This scoping review followed the 5-step Arksey and O'Malley framework and was submitted following PRISMA ScR. Five electronic databases were thoroughly searched. Papers are included if they are eligible. The result was a synthesis of descriptive and narrative elements. Results: 1117 papers were collected in total. Nine randomized controlled trial studies met the review's inclusion criteria. The papers included are sourced from reputable, relevant sources. As a whole, intermittent fasting appears to benefit improved insulin resistance in healthy obese adults. Intermittent fasting has been shown to reduce insulin levels while increasing insulin sensitivity, therefore improving insulin resistance. Conclusion: Evidence suggests that intermittent fasting can help improve insulin resistance in healthy obese adults.

The effects of shift work on sleep quality, diet quality, and obesity-related factors: A male population study

ABSTRACT Recent studies suggest that shift working may trigger health issues through disrupted circadian rhythms and altered eating habits. This study aimed to examine the possible associations of shift work with sleep quality, diet quality and obesity-related parameters. This study was conducted with 150 males (75 shift and daytime workers) aged 24–50 years. Dietary intake was determined using the 24-hour recall method, and dietary quality was evaluated using the Healthy Eating Index-2010 (HEI-2010). Anthropometrical measurements and body composition were assessed. The Pittsburgh Sleep Quality Index was used to evaluate sleep quality. Fasting and postprandial glucose and insulin, and fasting lipid levels were analyzed. HOMA-IR was calculated, and blood pressure was measured. The total HEI-2010 score of shift workers (52.6 [45.4–58.8]) was lower than the daytime workers (55.9 [49.1–64.9]) (p = 0.016). Among individuals with good sleep quality, the total HEI-2010 score, seafood and plant proteins, fatty acids, and sodium scores were lower in shift workers compared to others (p < 0.05 for each). Non-obese shift workers had higher body weight, waist circumference, waist/hip ratio, VLDL-cholesterol, triglyceride, postprandial glucose, and insulin levels compared to daytime workers (p < 0.05 for each). This study demonstrates that shift working is associated with lower diet quality independent of sleep quality.

Causal associations between insulin and Lp(a) levels in Caucasian population: a Mendelian randomization study

BackgroundNumerous observational studies have demonstrated that circulating lipoprotein(a) [Lp(a)] might be inversely related to the risk of type 2 diabetes (T2D). However, recent Mendelian randomization (MR) studies do not consistently support this association. The results of in vitro research suggest that high insulin concentrations can suppress Lp(a) levels by affecting apolipoprotein(a) [apo(a)] synthesis. This study aimed to identify the relationship between genetically predicted insulin concentrations and Lp(a) levels, which may partly explain the associations between low Lp(a) levels and increased risk of T2D.MethodsIndependent genetic variants strongly associated with fasting insulin levels were identified from meta-analyses of genome-wide association studies in European populations (GWASs) (N = 151,013). Summary level data for Lp(a) in the population of European ancestry were acquired from a GWAS in the UK Biobank (N = 361,194). The inverse-variance weighted (IVW) method approach was applied to perform two-sample summary-level MR. Robust methods for sensitivity analysis were utilized, such as MR‒Egger, the weighted median (WME) method, MR pleiotropy residual sum and outlier (MR-PRESSO), leave-one-out analysis, and MR Steiger.ResultsGenetically predicted fasting insulin levels were negatively associated with Lp(a) levels (β = − 0.15, SE = 0.05, P = 0.003). The sensitivity analysis revealed that WME (β = − 0.26, SE = 0.07, P = 0.0002), but not MR‒Egger (β = − 0.22, SE = 0.13, P = 0.11), supported a causal relationship between genetically predisposed insulin levels and Lp(a).ConclusionOur MR study provides robust evidence supporting the association between genetically predicted increased insulin concentrations and decreased concentrations of Lp(a). These findings suggest that hyperinsulinaemia, which typically accompanies T2D, can partially explain the inverse relationship between low Lp(a) concentrations and an increased risk of T2D.

Global 13C tracing and metabolic flux analysis of intact human liver tissue ex vivo.

Liver metabolism is central to human physiology and influences the pathogenesis of common metabolic diseases. Yet, our understanding of human liver metabolism remains incomplete, with much of current knowledge based on animal or cell culture models that do not fully recapitulate human physiology. Here, we perform in-depth measurement of metabolism in intact human liver tissue ex vivo using global 13C tracing, non-targeted mass spectrometry and model-based metabolic flux analysis. Isotope tracing allowed qualitative assessment of a wide range of metabolic pathways within a single experiment, confirming well-known features of liver metabolism but also revealing unexpected metabolic activities such as de novo creatine synthesis and branched-chain amino acid transamination, where human liver appears to differ from rodent models. Glucose production ex vivo correlated with donor plasma glucose, suggesting that cultured liver tissue retains individual metabolic phenotypes, and could be suppressed by postprandial levels of nutrients and insulin, and also by pharmacological inhibition of glycogen utilization. Isotope tracing ex vivo allows measuring human liver metabolism with great depth and resolution in an experimentally tractable system.