Increased Serum Insulin Levels Research Articles

Organic vs. inorganic nitrates: Metabolic and vascular outcomes in STZ-induced diabetes in mice

BackgroundDiabetic animals often display dysregulated nitric oxide (NO) metabolism, contributing to vascular dysfunction. This study evaluates the metabolic and vascular effects of organic nitrate isosorbide mononitrate (ISMN) versus inorganic sodium nitrate (NaNO3) in mice with type 1 diabetes mellitus (T1DM) induced by streptozotocin (STZ). Experimental approachT1DM was induced in male C57Bl6 mice with STZ ip and confirmed by fasting glucose. Mice were treated with ISMN (10 mg·kg-1) or NaNO3 (85 mg·L-1) for 14 days. A combination of in vivo, in vitro, and ex vivo studies assessed cardiometabolic benefits. ResultsBoth nitrates reduced blood and urinary hyperglycemia in T1DM mice, with ISMN exhibiting more significant reductions in blood glucose. ISMN and NaNO3 similarly reduced water and food intake, urinary volume, glucose intolerance, and insulin resistance while increasing insulin and nitrite levels in serum and urine. Both nitrates improved endothelium-independent vascular function and attenuated reactive oxygen species (ROS) while increasing NO levels in the aortic rings of T1DM mice. Furthermore, both nitrates similarly reduced mean arterial pressure in T1DM mice. Conclusion and implicationsISMN and NaNO₃ have demonstrated comparable hypotensive and antioxidant effects, offering metabolic and vascular benefits in STZ-TDM1 mice. The more pronounced reduction in blood glucose with ISMN treatment compared to NaNO₃ is particularly promising. The antihyperglycemic effects of both nitrates were linked to increased serum insulin levels and enhanced insulin sensitivity. These results provide a foundation for future clinical studies to evaluate the potential of ISMN or NaNO3 as antidiabetogenic and antihypertensive adjuvant therapies in diabetic patients.

Comparative Effects of Extracts from Black Rice or Pathum Rice Combined with Cereals on Blood Glucose Levels, Serum Insulin Levels and Blood Chemistry in Diabetic Rats

Rice is one of the major cereal crops in several Asian countries. It contains a variety of nutrients and provides valuable health benefits. The antidiabetic activity of rice combined with cereals has not been studied. Therefore, the present study was carried out to determine and compare the effects of extracts from Black rice (BRE), Pathum rice (PTRE), Black rice combined with cereals (BRCE), and Pathum rice combined with cereals (PTRCE) on body weight, blood glucose levels, serum insulin levels and blood chemistry of Streptozotocin (STZ)-induced diabetic rats. The results revealed that BRCE exhibited the highest activity in reducing fasting blood glucose (FBG) levels and increasing serum insulin levels, and also recovered the lipid profiles, renal function and hepatic function resulting from STZ in the diabetic rats, followed by BRE, PTRCE and PTRE, respectively. Also, BRCE exhibited an activity with similar potential to Glibenclamide. The findings indicate that the rice extracts possess antidiabetic activity which exerts the activity by increasing serum insulin resulting in reduction of blood glucose. Rice combined with cereals provides better antidiabetic activity and could be a source of valuable antidiabetic materials. HIGHLIGHTS Extracts from Black rice and Pathum Thani fragrant rice exhibit antidiabetic activity in Streptozotocin-induced diabetic rats. Antidiabetic activity of the extracts from Black rice and Pathum Thani fragrant rice is due to an increase in insulin secretion. Black rice exhibits antidiabetic activity higher than Pathum Thani fragrant rice. Combination with cereals could enhance the antidiabetic activity of rice. The extracts from Black rice and Pathum Thani fragrant rice may be useful for the management of diabetes mellitus. GRAPHICAL ABSTRACT

Antihyperglycemic activity of a novel polyherbal formula (HF344), a mixture of fifteen herb extracts, for the management of type 2 diabetes: Evidence from in vitro, ex vivo, and in vivo studies

Antihyperglycemic effects of a novel polyherbal formula (HF344), comprising fifteen Thai herbal extracts, were elucidated for pharmacological mechanisms and potential for managing type 2 diabetes mellitus, by employing in vitro, ex vivo, and in vivo approaches. LC/MS analysis of HF344 extract revealed several phytoconstituents, with piperine identified as the major active compound. HF344 extract significantly enhanced insulin secretion in RINm5F cells in vitro and inhibited glucose uptake into the everted sacs of the mouse small intestine ex vivo in a concentration-dependent manner compared to the control (p < 0.05). It exhibited potent α-glucosidase inhibition in vitro, with an IC50 of 96.74 μg/mL. Moreover, HF344 extract upregulated mRNA levels of GLUT1 in L6 skeletal myoblasts, suggesting increased glucose uptake into skeletal muscle. In addition, in vivo antihyperglycemic effects were assessed in streptozotocin (STZ)-nicotinamide (NA)-induced diabetic mice. Acute oral toxicity testing confirmed the HF344 extract's safety, with an LD50 exceeding 2000 mg/kg. Oral administration of HF344 extract (500 and 1000 mg/kg) in STZ-NA-induced diabetic mice significantly reduced the area under the fasting blood glucose (FBG)-time curve (AUC) in the oral glucose tolerance test (OGTT) model and treatment for 28-day reduced the FBG levels as compared with control (p < 0.05). This was accompanied by increased serum insulin levels and improved insulin resistance. HF344 extract also demonstrated a concentration-dependent inhibitory effect on malondialdehyde (MDA) production in vitro, with an IC50 of 7.24 μg/mL. Oral treatment with HF344 extract decreased MDA production in the homogenized muscle ex vivo collected from STZ-NA-induced mice. Furthermore, pretreatment with HF344 extract effectively restored the survival of RINm5F cells from STZ-induced damage. These findings suggest that HF344 is a promising polyherbal formula for managing blood glucose levels, enhancing insulin production, and providing antioxidant benefits in T2DM. Further research is required to evaluate the clinical efficacy and safety profiles of HF344.

Disruption of insulin receptor substrate 2 (IRS2) causes non-obese type 2 diabetes with β-cell dysfunction in the golden (Syrian) hamster

Because of the advent of genome-editing technology, gene knockout (KO) hamsters have become attractive research models for diverse diseases in humans. This study established a new KO model of diabetes by disrupting the insulin receptor substrate-2 (Irs2) gene in the golden (Syrian) hamster. Homozygous KO animals were born alive but with delayed postnatal growth until adulthood. They showed hyperglycemia, high HbA1c, and impaired glucose tolerance. However, they normally responded to insulin stimulation, unlike Irs2 KO mice, an obese type 2 diabetes (T2D) model. Consistent with this, Irs2 KO hamsters did not increase serum insulin levels upon glucose administration and showed β-cell hypoplasia in their pancreas. Thus, our Irs2 KO hamster provide a unique T2D animal model that is distinct from the obese T2D models. This model may contribute to a better understanding of the pathophysiology of human non-obese T2D with β-cell dysfunction, the most common type of T2D in East Asian countries, including Japan.

Effects of Ethanolic Extract of Cyperus esculentus (Tiger Nut) Tubers on Blood Glucose Level and Lipid Profile in Alloxan-Induced Diabetes Mellitus in Male Wistar Rats

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia. The prevalence of Diabetes mellitus is expected to increase to 5.3% by 2030. This study aimed to determine the effects of ethanolic extract of Cyperus esculentus tubers on alloxan-induced diabetes mellitus and lipid profile in male Wistar rats. A total of 25 Wistar rats were used for the study. Diabetes was induced by injection of alloxan 100 mg/kg and rats with blood glucose levels 200 mg/kg and above were considered diabetic. The rats were randomly divided into five groups (n = 5), group 1, normal control, group II, negative (diabetic) control, and Group III and Group IV were diabetic rats treated with 400mg/Kg and 800mg/Kg body weight of the ethanolic extract of Cyperus esculentus tubers and group V were diabetic rats treated with 10mg/Kg body weight Metformin. All treatments lasted for 28 days and Blood glucose levels were checked at weeks 0, 1, 2, 3, and 4 respectively. At the end of the treatment period, the rats were sacrificed and the blood samples collected were used to determine serum insulin level and lipid profile. The result obtained revealed a statistically significant (P&lt;0.05) decrease in blood glucose levels in groups III, IV, IV, and V as compared to the diabetic untreated group. The results of serum total cholesterol revealed a significant decrease in group I and group IV. However, high-density lipoprotein shows a significant decrease in group V as compared to the diabetic untreated group. There was also a statistically significant decrease (P&lt;0.05) in low-density lipoprotein (LDL) levels in groups I, III, and IV when compared with the diabetic untreated group. There was also a statistically significant (p &lt; 0.05) increase in serum insulin level in the normal control group and the group treated with 800mg/kg of extract. This study revealed the potential benefits of the ethanolic extract of Cyperus esculentus tubers in reducing blood glucose levels and its effects in reversing hyperlipidemia associated with diabetes mellitus.

Study of amino acids absorption and gut microbiome on consumption of pea protein blended with enzymes-probiotics supplement.

The current randomized, double-blind, crossover clinical trial was conducted to evaluate changes in the amino acid absorption and gut microbiota on consumption of pea protein supplemented with an enzymes-probiotics blend (Pepzyme Pro). A total of 15 healthy subjects were instructed to take test (pea protein + Pepzyme Pro) or placebo (pea protein + maltodextrin) for 15 days with a 30-day washout period. Blood samples were analyzed for plasma-free amino acids, insulin, and C-reactive protein (CRP). Additionally, nitrogen levels in urine and feces, along with the composition of gut microbiota, were evaluated. On day 15, the test arm showed a tendency to increase the rate of absorption and total absorption (AUC) of amino acids compared with the placebo arm, though the increase was statistically insignificant. In addition, 15-day test supplementation showed a tendency to reduce Tmax of all the amino acids (statistically insignificant except alanine, p = 0.021 and glycine, p = 0.023) in comparison with the placebo supplementation. There were no changes in urine and fecal nitrogen levels as well as serum CRP levels in the test and placebo arm. The increase in serum insulin level after 4 h was statistically significant in both arms, whereas the insulin level of the placebo and test arm at 4 h was not statistically different. Supplementation showed changes with respect to Archaea and few uncharacterized species but did not show statistically significant variations in microbiome profile at the higher taxonomic levels. A study with large sample size and detailed gut microbiome analysis is warranted to confirm the results statistically as well as to characterize altered species. However, the current study could provide an inkling of a positive alteration in protein digestibility, amino acid absorption, and gut microbiome with regular consumption of protein and enzymes-probiotics blend. Clinical Trial Registration:clinicaltrials.gov/; identifier [CTRI/2021/10/037072].

Impact of High-Intensity Interval Training on GLP-1R/ PKBα Axis in Pancreatic Tissue of Diabetes Rats Induced by High-Fat Diet and STZ

Objective: Apart from hormonal factors and oxidative stress, insulin synthesis is strongly dependent on transcription factors in the pancreas. The aim of the present study was to assess the impact of high-intensity interval training (HIIT) on genes affecting insulin synthesis in diabetic obese rats.&#x0D; Materials and Methods: Type 2 diabetes (T2D) was induced by a 6-week high-fat diet (HFD) and intraperitoneal injection of streptozotocin (25 mg /kg) in 14 male Wistar rats (10 week old, 220±10 g). Rats with fasting glucose levels between 400 and 150 were considered T2D. The diabetic rats were randomly assigned to exercise (HIIT: 6 weeks/5 sessions weekly, n= 7) or control (n= 7) groups. Forty-eight hours after the intervention, fasting GLP-1R and PKBα gene expression in pancreatic tissue and plasma insulin and glucose levels were compared between the groups. Data were compared by independent t-test used to compare variables, version 22 between groups. A P&lt; 0.05 was considered significant.&#x0D; Results: HIIT led to significant increase in PKBα gene expression (P: 0.001) and insulin (P: 0.031) and decreases in glucose concentration (P: 0.001) compared with the control group. No change was observed in the GLP-1R gene expression response to HIIT (P: 0.093).&#x0D; Conclusion: HIIT is associated with increased serum insulin levels in T2D obese rats. Despite no change in GLP-1R, this improvement is probably rooted in increased expression PKBα in pancreas in response to this type of exercise training

Ameliorative Effects of Cumin Extract-Encapsulated Chitosan Nanoparticles on Skeletal Muscle Atrophy and Grip Strength in Streptozotocin-Induced Diabetic Rats.

Skeletal muscle atrophy is a disorder characterized by reductions in muscle size and strength. Cumin extract (CE) possesses anti-inflammatory, antioxidant, and hypoglycemic properties. Its pharmaceutical applications are hindered by its low water solubility and by its cytotoxicity when administered at high doses. In this study, we have developed a simplified water distillation method using a rotary evaporator to isolate the active components in cumin seeds. The anti-inflammatory effects of CE and its potential to ameliorate skeletal muscle atrophy in rats with streptozotocin (STZ)-induced diabetes were evaluated. The half-maximal inhibitory concentration (IC50) of CE for cells was 80 μM. By encapsulating CE in chitosan nanoparticles (CECNs), an encapsulation efficacy of 87.1% was achieved with a slow release of 90% of CE after 24 h of culturing, resulting in CECNs with significantly reduced cytotoxicity (IC50, 1.2 mM). Both CE and CECNs significantly reduced the inflammatory response in interleukin (IL)-6 and IL-1β assays. STZ-induced diabetic rats exhibited sustained high blood glucose levels (>16.5 mmol/L), small and damaged pancreatic β islets, and skeletal muscle atrophy. CE and CECN treatments ameliorated skeletal muscle atrophy, recovered muscle fiber striated appearance, increased grip strength, and decreased IL-6 level. Furthermore, CE and CECNs led to a reduction of damage to the pancreas, restoring its morphological phenotype, increasing serum insulin levels, and lowering blood glucose levels in STZ-induced diabetic rats. Taken together, treatment with CECNs over a 6-week period yielded positive ameliorative effects in STZ-induced rats of muscle atrophy.

A low-carb diet increases fecal short-chain fatty acids in feces of obese women following a weight-loss program: randomized feeding trial

To compare fecal level of short-chain fatty acid (SCFA) and some serum inflammatory markers between the low-carbohydrate (LCD) and the habitual (HD) diet, subjects were enrolled from our previous study on the effect of LCD vs. HD on gut microbiota in obese women following an energy-restricted diet. Serum interleukin-6 (IL-6) significantly increased in the HD group (p < 0.001). Adjusted for the baseline parameters, fecal level of butyric, propionic, and acetic acid were significantly different between the LCD and HD groups (p < 0.001, p = 0.02, and p < 0.001, respectively). Increase in serum insulin level correlated with decrease in fecal propionic acid by 5.3-folds (95% CI = − 2.7, − 0.15, p = 0.04). Increase in serum high sensitive C-reactive protein (hs-CRP) correlated with decrease in the percentage of fecal butyric acid by 25% (p = 0.04). Serum fasting blood sugar (FBS) and insulin showed a significant effect on fecal acetic acid (p = 0.009 and p = 0.01, respectively). Elevated serum FBS and insulin correlated with increase in fecal acetic acid by 2.8 and 8.9-folds (95%CI = 0.34, 1.9 and 1.2, 9.2), respectively. The LCD increased fecal SCFAs and a significant correlation was seen between serum IL-6 and fecal propionic acid level. More studies are needed to reach a concise correlation.Trial registration number: The trial was registered in Iranian ClinicalTrials.gov IRCT20200929048876N3.

The antidiabetic effect of methanolic extract of Holarrhena pubescens seeds is mediated through multiple mechanisms of action

Holarrhena pubescens is widely used in Indian and Chinese medicine in the treatment of diabetes. The current work determined the oral hypoglycemic and antidiabetic effects of seed extract in rats. The probable mechanism of action was evaluated in-vitro by α - glucosidase inhibition, glucose metabolism in insulinoma (INS-1) cells to reflect secretion of insulin, and protein glycation inhibition. Its potential for herb-drug interaction was evaluated in the cytochrome P450 3A4 (CYP3A4) inhibition assay. The seed extract increased serum insulin levels and reduced serum blood glucose levels in the oral glucose tolerance test. It also reduced the serum glucose levels in streptozocin-induced diabetes. The extract also inhibited α –glucosidase enzyme activity and demonstrated that it can increase the secretion of insulin from INS to 1-rat insulinoma cell line cells in-vitro in a concentration-dependent manner. However, it had a very weak inhibitory effect on protein glycation and it did not affect the activity of CYP3A4. The results of the study showed that H. pubescens seed extract increases insulin secretion and inhibits glucose absorption both in-vivo and in-vitro with a weak protein glycation inhibitory effect. The herb is devoid of CYP3A4 inhibitory effect indicating that it may not have pharmacokinetic interaction with the drug metabolized by this enzyme.

Simiao Wan and its ingredients alleviate type 2 diabetes mellitus via IRS1/AKT2/FOXO1/GLUT2 signaling.

Type 2 diabetes mellitus (T2DM) is a metabolic disease. Simiao Wan (SMW) is a commonly used clinical drug for hyperuricemia treatment. SMW has been confirmed to improve insulin resistance and is expected to be a novel hypoglycemic agent. However, the hypoglycemic bioactive ingredients and mechanisms of action of SMW are unclear. To explore the hypoglycemic effects and reveal the mechanisms of SMW and bioactive ingredients (SMW-BI). The hypoglycemic effects of SMW and SMW-BI were verified in a mouse model of T2DM induced by streptozotocin (STZ) and a high-fat and high-sugar diet (HFSD). Network pharmacology was used to predict the mechanisms of SMW and SMW-BI. Histological analysis and real-time quantitative polymerase chain reaction (RT-qPCR) verified network pharmacology results. RT-qPCR results were further verified by immunofluorescence (IFC) and molecular docking. The correlation between proteins and biochemical indicators was analyzed by Spearman's correlation. Chlorogenic acid, phellodendrine, magnoflorine, jateorhizine, palmatine, berberine, and atractydin were identified as SMW-BI. After 8 weeks of treatment, SMW and SMW-BI decreased the levels of fasting blood glucose (FBG), total cholesterol (TC), triacylglycerols (TG) and low-density lipoprotein cholesterol (LDL-C), increased the level of high-density lipoprotein cholesterol (HDL-C), alleviated weight loss, and increased serum insulin levels in T2DM mice. In addition, SMW and SMW-BI improved hepatocyte morphology in T2DM mice, decreased the number of adipocytes, and increased liver glycogen. Network pharmacological analysis indicated that SMW and SMW-BI may exert hypoglycemic by regulating insulin receptor substrate 1 (IRS1)/RAC-beta serine/threonine-protein kinase (AKT2)/forkhead box protein O1 (FOXO1)/glucose transporter type 2 (GLUT2) signaling. Moreover, correlation analysis showed that SMW and SMW-BI were associated with activation of IRS1, AKT2, and GLUT2, and inhibiting FOXO1. RT-qPCR revealed that SMW and SMW-BI could increase levels of IRS1, AKT2, and GLUT2 in the livers of T2DM mice and lower the level of FOXO1. Furthermore, immunofluorescence analysis showed that FOXO1 expression in the livers of T2DM mice decreased after oral administration of SMW and SMW-BI. Furthermore, molecular docking showed that SMW-BI could bind directly to IRS1 and AKT2. SMW and SMW-BI are potential hypoglycemic drugs that alleviate T2DM by regulating IRS1/AKT2/FOXO1 signaling. Our study provides a research idea for screening the bioactive ingredients in traditional Chinese medicine (TCM).

The effects of sleep deprivation on insulin, resistin and visfatin levels in healthy humans

The Effects of Sleep Deprivation on Insulin, Resistin and Visfatin Levels in Healthy Humans ABSTRACT Background: Sleep deprivation is known to affect circulating insulin and glucose levels which in turn modulate glucose metabolism. However, the mechanism of alterations in glucose homeostasis during sleep deprivation is not known. In this study, we investigated circulating resistin and visfatin levels in response to 40 hours of sleep loss in order to shed light on the above-mentioned mechanism. Methods: This study included 12 healthy young adult subjects (aged between 18-32 years). All participants underwent polysomnographic evaluation and oral glucose tolerance test and then fasting venous blood samples were collected in morning hours. Then, subjects remained awake for 40 hours under actigraphic monitorization. At the end of sleep deprivation, blood samples were collected again. Serum insulin, resistin and visfatin levels were measured in all blood samples. Insulin was determined by chemical immune assay method, whereas resistin and visfatin levels assayed by ELISA. Results: Compared to baseline, 40-hour total sleep deprivation resulted in a significant increase in serum insulin levels (10.75±7.75 vs 35.98±27.96 IU; p=0.002) and a significant decrease in resistin levels (21.94±7.65 vs 11.71±5.31 IU; p=0.002). Visfatin levels remained unchanged (6.29±3.31 vs 5.43±5.08 IU; p&amp;gt;0.05). Conclusion: These results suggested that short-term total sleep deprivation may lead to insulin resistance which was evidenced by a significant increase insulin levels independent of resistin. This may contribute to pathophysiology of type 2 diabetes mellitus under conditions of chronic sleep deprivation.

Ferulic acid improves glucose homeostasis by modulation of key diabetogenic activities and restoration of pancreatic architecture in diabetic rats.

There are increasing concerns on the rising cases of diabetes mellitus with type 2 diabetes (T2D) being of major interest as well as the cost of its treatment. Plant phenolic compounds are natural and potent antioxidants that have been widely reported for their antidiabetic activities properties, one of which is ferulic acid. The effect of ferulic acid (FA) on major diabetogenic activities and pancreatic architecture linked to T2D was investigated in T2D rats. T2D was induced in male Sprague-Dawley rats using the fructose-streptozotocin model. Diabetic rats were treated with FA at 150 or 300 mg/kg bodyweight (bw). Normal control consisted of rats administered with food and water, while diabetic control consisted of untreated diabetic rats. Metformin was used as the standard drug. The rats were humanely sacrificed after 5weeks of treatment. Their blood, liver, and pancreas were collected for analysis. Total glycogen content and carbohydrate metabolic enzymes activities were analyzed in the liver, while the pancreas and serum from blood were analyzed for oxidative stress biomarkers, purinergic and cholinergic enzyme activities, and amylase and lipase activities. The pancreatic tissue was further subjected to microscopic and histological examinations. FA caused a significant (p < 0.05) decrease in blood glucose level, with concomitant increase in serum insulin level. Treatment with FA also led to elevated levels of GSH, HDL-c, SOD, and catalase activities, while concomitantly suppressing malondialdehyde, cholesterol, triglyceride, LDL-c, NO, ALT, AST, creatinine, urea, and uric acid levels, acetylcholinesterase, ATPase, ENTPDase, 5'-nucleotidase, lipase, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-biphosphatase activities. Histology analysis revealed an intact pancreatic morphology in FA-treated diabetic rats. While transmission electron microscopy (TEM) analysis revealed an intact pancreatic ultrastructure and increased number of insulin granules in β-cells. Taken together, these results portray that the antidiabetic potentials of ferulic acid involves modulation of major diabetogenic activities and maintenance of the pancreatic ultrastructure architecture.

Impaired hepatic glucose metabolism and liver-α-cell axis in mice with liver-specific ablation of the Hepatocyte Nuclear Factor 4α (Hnf4a) gene

BackgroundHnf4a gene ablation in mouse liver causes hepatic steatosis, perturbs HDL structure and function and affects many pathways and genes related to glucose metabolism. Our aim here was to investigate the role of liver HNF4A in glucose homeostasis. MethodsSerum and tissue samples were obtained from Alb-Cre;Hnf4afl/fl (H4LivKO) mice and their littermate Hnf4afl/fl controls. Fasting glucose and insulin, glucose tolerance, insulin tolerance and glucagon challenge tests were performed by standard procedures. Binding of HNF4A to DNA was assessed by chromatin immunoprecipitation assays. Gene expression analysis was performed by quantitative reverse transcription PCR. ResultsH4LivKO mice presented lower blood levels of fasting glucose, improved glucose tolerance, increased serum lactate levels and reduced response to glucagon challenge compared to their control littermates. Insulin signaling in the liver was reduced despite the increase in serum insulin levels. H4LivKO mice showed altered expression of genes involved in glycolysis, gluconeogenesis and glycogen metabolism in the liver. The expression of the gene encoding the glucagon receptor (Gcgr) was markedly reduced in H4LivKO liver and chromatin immunoprecipitation assays revealed specific and strong binding of HNF4A to the Gcgr promoter. H4LivKO mice presented increased amino acid concentration in the serum, α-cell hyperplasia and a dramatic increase in glucagon levels suggesting an impairment of the liver-α-cell axis. Glucose administration in the drinking water of H4LivKO mice resulted in an impressive extension of survival. The expression of several genes related to non-alcoholic fatty liver disease progression to more severe liver pathologies, including Mcp1, Gdf15, Igfbp-1 and Hmox1, was increased in H4LivKO mice as early as 6 weeks of age and this increased expression was sustained until the endpoint of the study. ConclusionsOur results reveal a novel role of liver HNF4A in controlling blood glucose levels via regulation of glucagon signaling. In combination with the steatotic phenotype, our results suggest that H4LivKO mice could serve as a valuable model for studying glucose homeostasis in the context of non-alcoholic fatty liver disease.

The acute effects of coffee consumption on blood glucose and it’s relationship with serum cortisol and insulin in females

This research was aimed at analyzing the acute effects of Arabica black coffee consumption on blood glucose, insulin, and serum cortisol levels, as well as determining the pharmacological effects of black coffee as an antihyperglycemic. A randomized control trial with healthy female subjects was used in this study. There were 20 volunteers in total: 9 as the control group and 11 as the trial group. The treatment included brewing 10 grams of Gayo Arabica black coffee powder with 150 ml of boiling water. Blood glucose, insulin, and cortisol levels were measured twice, before and after 60 minutes of coffee consumption. An independent sample t-test (p &amp;lt; 0.05), Pearson correlation test (p &amp;lt; 0.05), and simple linear correlation test (p &amp;lt; 0.05) were used to analyze the data. Blood glucose levels and serum cortisol levels decreased significantly after coffee consumption in the trial group (p = 0.002* and p = 0.001*). There was no significant negative correlation between glucose and insulin levels (r = -0.122; p = 0.721). On the other hand, there was a significant positive correlation between cortisol levels and blood glucose (r = 0.651; p = 0.002*). In conclusion, a single cup of Gayo Arabica black coffee reduces blood sugar and serum cortisol levels, but does not increase serum insulin levels. Blood glucose levels correlate positively with serum cortisol levels in healthy female.

β-Islet cell regeneration potential of Mirabilis jalapa in hyperglycemic rats

Objective: To investigate the role of Mirabilis jalapa root extracts in restoration of glucose homeostasis in alloxan-induced hyperglycemic Wistar albino rats. Methods: Experimental hyperglycemic rats were treated daily with 200 and 400 mg/kg of Mirabilis jalapa extracts after initial fasting for 6 h. Two-hour postprandial glucose and changes in body weight were monitored during treatment. After 14 d, the rats were sacrificed and blood was collected for biochemical assessment of serum glucose and insulin levels, lipid profile, and oxidative stress markers. Histopathological examinations of harvested pancreas were also carried out. Results: Mirabilis jalapa root extracts at 200 and 400 mg/kg increased the body weight of hyperglycemic rats. Postprandial glucose levels of the extract-treated hyperglycemic groups progressively declined during treatment compared with the untreated hyperglycemic control group (P&lt;0.05). The lipid profile indices of the untreated negative control group were significantly elevated (P&lt;0.05), which were reversed by treatment with Mirabilis jalapa extracts. The remarkable increases in antioxidant enzyme activities and a significant decrease in malondialdehyde levels were observed in the hyperglycemic group treated with Mirabilis jalapa extracts. Mirabilis jalapa extracts also significantly increased serum insulin levels (P&lt;0.05). In addition, histopathological examinations of the pancreas revealed a significant cell population within the islet nests of the extract-treated hyperglycemic groups. Conclusions: Mirabilis jalapa extract can restore glucose homeostasis and show hypoglycemic and hypolipidemic effects in hyperglycemic rats. Further studies are needed to verify the active components of the plant and the underlying mechanism of action in the future.

Potential mechanism of Jatropha gossypifolia phenolic derivatives in enhancing insulin-signalling cascades GLUT 4, IRβ and GSK-3β in streptozotocin nicotinamide induced type II diabetic in wistar rat model

ObjectiveDiabetes mellitus is a metabolic syndrome that alters the composition of carbohydrates, proteins and fat content in the body due to decreased insulin secretion. This disrupts the insulin-signaling cascade, resulting in failure in the targeted tissues, such as insulin-stimulated glucose absorption muscle and fat. Natural products such as plants, which are rich in nutrient, offer a wide range of treatments for a number of diseases and infections including diabetes mellitus. Hence, this study investigates the anti-hyperglycemic efficacy of the methanolic leaves extract of Jatropha gossypifolia in experimental diabetic rats. MethodsPhytochemical constitution of J. gossypifolia showed tannin content to be significantly increased in methanolic extract and HPLC analysis also revealed phenolic derivative tannic acid to be main constitution. An intraperitoneal administration of 110 mg/kgbody weight (b.w) nicotinamide and 45 mg/kg b.w. streptozotocin was provided to male Wistar albino rats, thus inducing diabetic. Diabetic induced rats treated with methanolic leaves extract of J. gossypifolia at the concentration between 100 and 50 mg/kg for 35 days. Periodic blood glucose level and body weight were measured. Methanolic extract influence was evaluated with q-PCR and western blot analysis on the cellular targets of insulin signaling cascades. ResultsThe results showed the decrease in blood glucose levels and increased serum insulin level in treated groups was significant (P < 0.05) in oral administration of methanol extract. Methanolic extract exhibited a profound increase in the gene expression of the cellular targets of insulin signaling cascade including IRTK, IRS1, PI3K, GS, GLUT 4 and a basal level expression of GSK-3β. In addition, methanolic extract increased protein expression of IRβ (2.7-fold), GSK-3β (2.5-fold) and GLUT 4 (2.4-fold) translocation as evidenced from western blot analysis with the plasma membrane fractions. ConclusionConclusively, methanolic leaves extract of J. gossypifolia exhibited a profound anti-hyperglycemic activity by modulating the expression of the key targets of insulin signaling pathway.

The role of pancreas to improve hyperglycemia in STZ-induced diabetic rats by thiamine disulfide

BackgroundThe present study investigated the effect of thiamine disulfide (TD) on the pancreas in terms of hyperglycemia improvement and insulin sensitivity increase in diabetic male rats. We also aimed to study the function of Pdx1 (pancreatic and duodenal homeobox 1) and Glut2 (glucose transporter 2) genes in pancreatic tissue.MethodsType 1 diabetes was induced through injection of 60 mg/kg streptozotocin (STZ). The diabetic rats were divided into four groups, namely diabetic control (DC), diabetic treated with thiamine disulfide (D-TD), diabetic treated with insulin (D-insulin), and diabetic treated with TD and insulin (D-insulin+TD). The non-diabetic (NDC) and diabetic groups received a normal diet (14 weeks). Blood glucose level and body weight were measured weekly; insulin tolerance test (ITT) and glucagon tolerance test (GTT) were performed in the last month of the study. The level of serum insulin and glucagon were measured monthly and a hyperglycemic clamp (Insulin Infusion rate (IIR)) was done for all the groups. Pancreas tissue was isolated so that Pdx1and Glut2 genes expression could be measured.ResultsWe observed that TD therapy decreased blood glucose level, ITT, and serum glucagon levels in comparison with those of the DC group; it also increased serum insulin levels, IIR, and expression of Pdx1 and Glut2 genes in comparison with those of the DC group.ConclusionAdministration of TD could improve hyperglycemia in type 1 diabetic animals through improved pancreas function. Therefore, not only does TD have a significant effect on controlling and reducing hyperglycemia in diabetes, but it also has the potential to decrease the dose of insulin administration.

Micronized Dietary Okara Fiber: Characterization, Antioxidant, Antihyperglycemic, Antihyperlipidemic, and Pancreato-Protective Effects in High Fat Diet/Streptozotocin-Induced Diabetes Mellitus.

Diabetes mellitus (DM) is a lifelong devastating and debilitating disease with serious chronic complications. Okara is a byproduct generated from soymilk or tofu production and it has been reported to have antioxidant and lipid-lowering effects. However, the antidiabetic effects and pancreatic β-cells’ secretory functions of micronized okara fiber (MOF) have not been reported. Therefore, this study explored the antidiabetic effects and modulatory potentials of MOF on pancreatic β-cells’ secretory functions in a high fat/high sugar/streptozotocin rat model of diabetes mellitus. Fiber-rich okara was prepared by removing fat and proteins from freshly obtained okara, followed by micronization. Fiber-rich okara was prepared, micronized, and characterized for hydrophobicity, thermal stability, structure–function relationship, and antioxidant potentials. We then established a rat model of DM and MOF and two doses (100 and 400 mg kg–1) were administered to see its anti-DM effect. Four weeks of MOF supplementation significantly reduced blood glucose, increased serum insulin level, improved hepatorenal functions, glucose tolerance, and regenerated pancreatic β-cells in the treated DM rats. Furthermore, MOF significantly improved the pancreatic antioxidant defense system by significantly elevating glutathione peroxidase, catalase, and superoxide dismutase activities while depleting the malonaldehyde level in the pancreas of the treated diabetic rats. Our results indicated that MOF ameliorated DM by impeding hyperglycemia, hyperlipidemia, and oxidative stress and enhancing the secretory functions of the beta cells, suggesting that MOF might be used as a protective nutrient in DM.

Effects of Porphyra yezoensis extract on hepatic inflammatory factors and oxidative stress in type 1 diabetic mice

To study the effect of Porphyra yezoensis extract on liver inflammation and oxidative stress in type 1 diabetics mice. A total of ninety-one C57 BL/6 J male mice were adaptively fed for two weeks, and twelve C57 BL/6 J male mice were randomly reserved to be included in the blank control group. The rest of the mice were fasted overnight for twelve hours(except water), and they were given 170.00 mg/kg streptozotocin by intraperitoneal injection. Fasting blood glucose in type 1 diabetics mice were greater than or equal to 16.7 mmol/L after seven days, and polydipsia, polyphagia, polyuria and weight loss appeared, which were judged to be the successful model of type 1 diabetes. Forty-eight successfully modeled mice were divided into the model control group, the low dose of Porphyra yezoensis extract group, the medium dose of Porphyra yezoensis extract and high dose of Porphyra yezoensis extract group according to the fasting blood glucose and body weight. The mice in the blank control group and the model group were given the same amount of normal saline. The low-dose, medium-dose, and high-dose intervention groups were separately given the corresponding dose of Porphyra yezoensis extract by intragastric administration for six weeks. The body weight of type 1 diabetic mice, changes in body length, fasting blood glucose, insulin, liver inflammatory factors and oxidative stress indicators and pathological sections of liver and pancreas after the intervention of Porphyra yezoensis extract were observed. The glucose oxidase method was used to determine the fasting blood glucose level of type 1 diabetic mice. The serum insulin content, liver inflammatory factor levels and oxidative stress indicators were detected by the enzyme-linked immunosorbent assay(ELISA). The hematoxylin-eosin staining method was used to observe histopathology of liver and pancreas paraffin sections. The weight of the model control group was significantly lower than that of the blank control group(P&lt;0.05), and the fasting blood glucose value was significantly higher than that of the blank control group(P&lt;0.05). There was no statistical difference. In terms of inflammatory factors, compared with the model control group, low-dose Porphyra yezoensis extract can increase serum insulin levels and reduce liver tumor necrosis factor-α(TNF-α) levels(P&lt;0.05) in T1DM mice, and medium-dose Porphyra yezoensis extract can reduce liver TNF-α level(P&lt;0.05), high-dose Porphyra yezoensis extract can reduce the level of interleukin-1β(IL-1β)(P&lt;0.05). The histopathological conditions of pancreas in different intervention groups were improved compared with the model control group, and the number of β cells increased compared with the model group. In terms of oxidative stress, compared with the model control group, low-dose Porphyra yezoensis extract can significantly reduce the levels of liver alanine aminotransferase(ALT) and malondialdehyde(MDA)(P&lt;0.05), and high-dose Porphyra yezoensis extract can significantly increase the levels of glutathione peroxidase(GSH-Px) and catalase(CAT)(P&lt;0.05). The protective effect of Porphyra yezoensis extract on liver oxidative damage in T1DM mice may be achieved by regulating the activity of CAT and GSH-Px and reducing the content of MDA. In addition, Porphyra yezoensis extract can reduce liver TNF-α and IL-1β levels to improve liver inflammation.