Decreased Blood Glucose Research Articles

The Effect of Cooking and Cooling Chickpea Pasta on Resistant Starch Content, Glycemic Response, and Glycemic Index in Healthy Adults

Background/Objectives: Legume seeds, such as chickpeas, are a rich source of resistant starch (RS) and have a low glycemic index (GI). The aim of this study was to evaluate the effect of cooking and cooling chickpea pasta on the RS content, glycemic response, and GI in healthy subjects. Methods: Twelve healthy subjects of both sexes, aged 18–65 years, participated in this study. Each person consumed two standardized portions of chickpea pasta: (i) freshly cooked (FCP) and (ii) cooked chickpea pasta which was cooled for 24 h at 4 °C and reheated before consumption (CCP). Glucose solution was provided as a reference food. Participants consumed chickpea pasta in a random order. GI measurements were completed using the standard methodology and calculated according to the ISO 2010 standard. Results: The cooling and reheating process significantly increased the RS content of boiled chickpea pasta (from 1.83 g/100 g to 3.65 g/100 g) and had a beneficial effect on postprandial glycemia in healthy individuals. The CCP pasta had a significantly lower GI value than the FCP pasta (33 vs. 39, p = 0.0022). A significant difference in the glucose, as identified by the incremental area under the curve (IAUC), was observed between the CCP and FCP (1327.9 ± 414.8 mg/dL/min vs. 1556.1 ± 456.9 mg/dL/min, p = 0.0022). The cooling–reheating process did not affect the sensory attributes of the chickpea pasta. In general, the overall acceptability of the CCP pasta was similar to that of the FCP pasta. Conclusions: The results of our study support the hypothesis that a reduced glycemic response after simple changes in technological intervention leads to a decrease in postprandial blood glucose and GI. This can be helpful for people who need to control postprandial glycemia.

Gymnema lactiferum: A Review of Its Traditional Applications, Phytochemical Constituents, and Biological Properties

ABSTRACTHumanity has a longstanding reliance on natural plants for medicinal purposes, and Gymnema lactiferum (G. lactiferum) has emerged as a medicinal plant with deep‐rooted traditional usage. Throughout history, this plant has been an integral part of traditional medical systems, demonstrating diverse therapeutic effects. Notably, among these effects is its ability to decrease blood glucose concentration in diabetic patients, impart cooling effects, serve as an anabolic and rehydrating agent, stimulate spermiogenesis, and exhibit wormicidal properties. Furthermore, G. lactiferum has been used in treating conditions such as hemorrhoids cancers, anorexia, and as a cardiac stimulant. The primary objective of this review is to comprehensively gather and critically assess research findings regarding the medicinal properties of G. lactiferum, specifically emphasizing the bioactive compounds responsible for these properties. Previous studies have documented the presence of various phytochemicals in G. lactiferum, which are associated with some biological activities, including antioxidative, anti‐hyperglycemic, cholesterol‐regulating, and anti‐inflammatory properties. Additionally, this review explores potential future applications for this plant. Beyond its medicinal significance, extracts derived from G. lactiferum demonstrate promise for future nutritional applications. This review highlights the potential use of G. lactiferum as an herbal medicine by critically assessing research on its medicinal value.

Postprandial Symptoms in a Mixed-Meal-Test after Bariatric Surgery - Clinical Experience and a Critical Review of Dumping Syndrome Definition and Management.

Introduction Despite recent attempts to reach a consensus on the diagnostic criteria and treatment of Dumping Syndrome (DS) after bariatric surgery, many questions about the clinical applicability and significance of standardized provocation tests remain unanswered. The objective of this study is to retrospectively evaluate a mixed-meal-test (MMT) based on general nutritional recommendations after bariatric surgery and its clinical value in diagnosing DS. Methods The MMT contained 15.5g of protein, 10g of fat, 20.7g of carbohydrates, and 3.1g of dietary fiber, totaling 241 kcal. Symptoms based on the Sigstad Score, along with blood sugar, hematocrit, pulse rate, and blood pressure, were collected as primary readouts. The analysis included 58 MMTs from 56 patients who reported postprandial symptoms indicative of DS and were referred to the clinic by surgeons or general practitioners. Results Although all individuals reported significant symptoms at home, the MMT showed a positive symptom score (Sigstad Score ≥7) in only 16 cases (28%). Neither a heart rate increase >10 BPM nor the 3% hematocrit increase suggested as cut-offs for early DS by the consensus paper were associated with the Sigstad Score or individually reported symptoms. None of the participants had a glucose decrease below 50 mg/dl; one fell below 60 mg/dl and 14 fell below 70 mg/dl. A blood glucose decrease below 70 mg/dl was not associated with symptoms. Conclusion The MMT showed that only a minority of patients reported classical DS symptoms under controlled conditions. Changes in hematocrit, heart rate, and blood sugar decrease below 70mg/dl did not help to predict symptoms in the individuals studied. The data, in the context of existing evidence, suggest that provocation tests have little value in clinical practice and that DS as a clinical entity after bariatric surgery should be reevaluated.

Therapeutic Effects of Proanthocyanidins on Diabetic Erectile Dysfunction in Rats.

The rising occurrence of erectile dysfunction related to diabetes mellitus (DMED) has led to the creation of new medications. Proanthocyanidins (PROs) is a potential agent for DMED. In this study, the DMED rat model was established using streptozotocin (STZ) and erectile function was assessed using apomorphine (APO) in rats. Following this, the rats were subjected to oral treatment with PRO. Then, we evaluated the influence of PROs on DMED rats. The findings suggest that PROs significantly enhance erectile function in DMED rats. PROs modulated glucose and lipid metabolism in DMED rats by decreasing blood glucose and lipid levels while increasing liver glycogen and serum insulin levels. Furthermore, PROs enhanced vascular endothelial function in DMED rats by augmenting nitric oxide (NO) levels and reducing the levels of endothelin-1 (ET-1) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Additionally, PROs have been shown to elevate testosterone (T) levels, mitigate pathological testicular damage, and enhance sperm concentration and survival rates. Finally, the core targets were screened using network pharmacology, followed by validation through molecular docking, enzyme-linked immunoassay (ELISA), and real-time PCR methodologies. Our findings imply that PROs may treat DMED by elevating AKT1 levels while concurrently diminishing CASP3 levels, thereby effectively regulating the PI3K-Akt signaling pathway. Overall, these results support using PROs as a potential candidate for the treatment of DMED.

SGLT2i and GLP1-RA exert additive cardiorenal protection with a RAS blocker in uninephrectomized db/db mice.

Diabetic Kidney Disease (DKD) is the main cause of end-stage renal disease in the developed world. The current treatment of the DKD with renin-angiotensin system (RAS) blockade does not totally halt the progression to end stage kidney disease. Currently, several drugs have shown to delay DKD progression such as sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like-1 receptor agonists (GLP-1RA). We hypothesized that by combining several drugs that prevent DKD progression on top of RAS blockade a synergistic effect would be achieved in terms of cardiorenal protection. In the present study, we analysed if the combination of a RAS blocker (ramipril) with a SGLT2i (empagliflozin) and/or GLP-1RA (semaglutide) in a type 2 diabetic mouse model could have add-on effects in kidney and heart protection. Male and female uninephrectomized type 2 diabetic db/db mice were treated with empagliflozin and/or semaglutide on top of ramipril during 8weeks. During the study body weight, water and food intake were weekly monitored, glycaemia biweekly and albuminuria and glomerular filtration rate (GFR) before and after the treatment. At the end of the experiment, kidney and heart were isolated for histological and gene expression studies as well as for intrarenal RAS state assessment. Semaglutide combined with ramipril and/or empagliflozin significantly decreased albuminuria but only when combined with both compounds, semaglutide further decreased blood glucose, glomerular hyperfiltration in male mice and glomerular mesangial matrix expansion. In kidney, only the triple treatment with empagliflozin, semaglutide and ramipril reduced the expression of the proinflammatory and profibrotic genes ccl2 and TGFß1. In addition, the combination of empagliflozin and semaglutide on top of RAS blockade was superior in decreasing cardiomyocyte hypertrophy and heart fibrosis in db/db mice. Our results suggest that the combination of SGLT2i with GLP-1RA is superior in cardiorenal protection in DKD than the drugs administered alone on top of RAS blockade.

A-079 Investigation of gut microbial flavonoid catabolites in metabolic diseases

Abstract Background Flavonoids, a secondary metabolite found in plant-based diets, have gained attention in the last decade for their antioxidative properties in high-fat diet induced obesity animal models and human studies. Previous work showed that certain gut microbiota members can metabolize flavonoids into monophenolic acids (MPAs), and some of these MPAs have similar effects to insulin when administered orally. Our objective is to explore the microbiome connection between flavonoid-rich diets and improved metabolic parameters in obesity. We hypothesize that flavonoid-supplemented diets are most effective in the presence of gut microbiota capable of MPA formation and that these bacterial metabolites are the main bioactive compounds responsible for the improved metabolic parameters Methods To investigate our hypothesis, we fed male and female C57BL/6 mice a high-fat control diet (HFD) or the same diet supplemented with 1% MPA or 1% berry extract for 12 weeks. Each group was further divided into subgroups that received regular drinking water (RW) or antibiotic water (ABW) to suppress gut microbial communities. A range of metabolic parameters, such as body weight, lean and fat mass, glucose and insulin tolerance, histological assessment of liver cells, quantification of liver injury biomarkers, transcriptional changes in metabolically active tissues, and glucose and lipid metabolism pathways, were monitored. Additionally, 16s sequencing was performed on the cecal microbial composition of each group. Results Mice on HFD control with RW or ABW showed prominent hepatic steatosis and an increase in liver lipids accumulation demonstrated by a significant decrease in the activation of lipid metabolism pathways. Similarly, mice on HFD with 1% MPA and RW or ABW exhibited a significant reduction in hepatic steatosis and an increase in the activation of the lipid metabolism pathways, regardless of gut microbiota presence. In line with our hypothesis, mice on HFD with 1% berry extract and RW showed a similar reduction in hepatic steatosis to both 1% MPA groups. However, mice on HFD with 1% berry extract and ABW displayed noticeable hepatic steatosis, indicating the loss of the positive effect provided by berry extract metabolites once gut microbiota was depleted by antibiotics. Insulin tolerance test revealed a gut microbial effect as well in the HFD with 1% berry extract, illustrated by a significant reduction in glucose levels after insulin injection and an increase in insulin sensitivity. In contrast, the HFD control mice experienced an increase in glucose levels after insulin injection and insulin resistance. Although there were notable decreases in fasting blood glucose, there were no significant effects on fat and lean mass, insulin, glucagon, or liver injury marker levels. Finally, the mice on HFD with 1% berry extract had significantly more diverse cecal microbial communities than those fed HFD or HFD with 1% MPA. Conclusions Feeding mice a flavonoid-rich diet in the presence of intact gut microbiome can improve metabolic parameters associated with metabolic diseases, potentially preventing, or reversing these diseases. Our findings suggest promising avenues for treatment, such as dietary flavonoid supplementation with concurrent gut microbial probiotic therapy.

Hypoglycemic activity of Garcinia mangostana L. extracts on diabetes rodent models: A systematic review and network meta-analysis.

Diabetes mellitus is a significant global health issue, and alternative treatments from natural products like Garcinia mangostana L. [Clusiaceae] or GM are being explored for their potential benefits. This study focused on evaluating the hypoglycemic effects of GM on diabetic rodent models. A comprehensive search was conducted in PubMed, Scopus, and Embase for studies reporting blood glucose levels within 2weeks as the primary outcome and changes in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) as secondary outcomes. A network meta-analysis (NMA) was performed to determine the pooled effectiveness of each intervention, estimating the weighted mean difference (WMD) and 95% confidence interval (CI) from both direct and indirect evidence. The surface under the cumulative ranking curve (SURCA) was used to rank the interventions. Ten articles were identified, with nine included for quantitative analysis. All GM extracts showed greater effectiveness than the control in decreasing blood glucose levels within 2weeks. GM at 200mg/kg (GM200) was the top-ranked extract for reducing glucose levels beyond 2weeks and increasing HDL-C levels. The ethanol extract of GM at 200mg/kg (GME200) was the most effective for blood glucose reduction within 2weeks and for TC and TG reductions. The methanol extract of GM at 200mg/kg (GMM200) was the top-ranked extract for LDL-C reductions. GM and its extracts demonstrated significant hypoglycemic activity and improvements in lipid profiles in diabetic rodent models, highlighting their potential as therapeutic agents for the prevention and treatment of diabetes mellitus. Further research in human trials is warranted to confirm these findings and establish clinical applications. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023426254.

Energy stress induced cardiac autophagy detection via a chronic and dynamic cardiomyocytes-based biosensing platform

Hypoglycemia is a common complication which occurs during the treatment of diabetes, closely associated with cardiovascular events. A sudden decrease in blood glucose increases the risk of arrhythmia, which can lead to sudden cardiac death. This event is usually accompanied by abnormal electrophysiological activities in cardiomyocytes. However, traditional models do not efficiently reflect real-time cardiomyocyte electrophysiological changes under various glucose deprivation conditions in a large-scale and high-throughput manner. Therefore, we need to develop a new biosensing platform to aid in related scientific research. In this study, a cardiomyocyte-based biosensor was developed for real-time, noninvasive monitoring of the electrophysiological responses of cardiomyocytes under different glucose concentrations. The findings show that low-glucose conditions result in abnormal electrophysiology in cardiomyocytes, but autophagy enables cells to survive this adversity. Inhibition of autophagy exacerbates electrophysiological abnormalities, and long-term glucose starvation causes irreversible damage to cardiomyocytes. The proposed chronic and dynamic cardiomyocyte-based biosensing platform provides a new tool for understanding the effects of hypoglycemia on the in vitro cardiomyocyte-based heart model, revealing that autophagy has the potential to be an alternative treatment for diabetes and hypoglycemia.

Curcumin extract improves beta cell functions in obese patients with type 2 diabetes: a randomized controlled trial

BackgroundType 2 diabetes mellitus (T2DM) is a chronic condition characterized by insulin resistance and impaired insulin production, leading to elevated blood glucose levels. Curcumin, a polyphenolic compound from Curcuma longa, has shown potential in improving insulin sensitivity and reducing blood glucose levels, which may help mitigate type 2 diabetes progression.ObjectiveTo assess the efficacy of improving type 2 diabetes (T2DM).Study designThis randomized, double-blind, placebo-controlled trial included subjects (n = 272) with criteria for type 2 diabetes.MethodsAll subjects were randomly assigned to receive curcumin (1500 mg/day) or placebo with blind labels for 12 months. To assess the improvement of T2DM after curcumin treatments body weight and body mass index, fasting plasma glucose, glycosylated hemoglobin A1c, β-cell function (homeostasis model assessment [HOMA-β]), insulin resistance (HOMA-IR), insulin, adiponectin, and leptin were monitored at the baseline and at 3-, 6-, 9-, and 12-month visits during the course of intervention.ResultsAfter 12 months of treatment, the curcumin-treated group showed a significant decrease in fasting blood glucose (115.49 vs.130.71; P < 0.05), HbA1c (6.12 vs. 6.47; P < 0.05). In addition, the curcumin-treated group showed a better overall function of β-cells, with higher HOMA-β (136.20 vs. 105.19; P < 0.01) The curcumin-treated group showed a lower level of HOMA-IR (4.86 vs. 6.04; P < 0.001) and higher adiponectin (14.51 vs. 10.36; P < 0.001) when compared to the placebo group. The curcumin-treated group also showed a lower level of leptin (9.42 vs. 20.66; P < 0.001). Additionally, body mass index was lowered (25.9 4 vs.29.34), with a P value of 0.001.ConclusionsA 12-month curcumin intervention in type 2 diabetes patients shows a significant glucose-lowering effect. Curcumin treatment appeared to improve the overall function of β-cells and reduce both insulin resistance and body weight, with very minor adverse effects. Curcumin intervention in obese patients with type 2 diabetes may be beneficial.Trial registrationThai clinical trials regentrify no.20140303003.

Antidiabetic and Hypolipidemic Effect of Ethanolic Seed Extract of Prosopis juliflora in Fructose Induced Hyperglycemia in Rats

Objective: To evaluate the antidiabetic and hypolipidemic effect of ethanolic seed extract of Prosopis juliflora in fructose induced hyperglycemia in wistar albino rats in comparison with Metformin. Materials and methods: 30 male wistar albino rats were divided equally into 5 groups. Group I and II were the normal and the disease control groups. While, groups III to V were the treatment groups. Animals in group I received regular drinking water; whereas, groups II to V received 20% fructose water for 8 weeks. After 8 weeks, animals in groups II to V had elevated fasting blood sugar, HOMA-IR, weight gain and dyslipidemia. From week 9 to 16 group I animals continued to receive regular drinking water, group II received 2ml of distilled water and groups III, IV and V received Metformin 200mg/kg, P.juliflora extract 400mg/kg and 600mg/kg respectively in addition to 20% fructose water. The animals were sacrificed at the end of 16 weeks and histopathological examination of pancreas was done. Biochemical and hematological assessments were done at baseline and at 16 weeks to assess safety of the interventions. Results: When compared to the disease control group, animals in group III treated with metformin and groups IV and V treated with P.juliflora extract at doses of 400mg/kg and 600mg/kg showed a significant decrease in Fasting blood glucose, HOMA-IR and improvement in lipid profile. Even though both the doses of the extract showed significant pharmacological activity, 600mg/kg showed better activity equivalent to metformin. Histopathological examination of pancreas showed regenerative changes in the metformin and P.juliflora 600mg/kg treated groups. No significant abnormality was observed in the biochemical and haematological parameters at the end of the study. Conclusion: P.juliflora seed extract in the dose 400 mg/kg and 600mg/kg exhibited antidiabetic and hypolipidemic activity with no significant adverse events, in this study. Both the doses were having anti dyslipidemic effect similar to metformin whereas 600 mg/kg dose of P.juliflora was having better antidiabetic effect comparable to Metformin. Keywords: Diabetes, Dyslipidemia, P.juliflora, Fructose, Metformin, Metabolic syndrome

Palmitic acid promotes miRNA release from adipocyte exosomes by activating NF-κB/ER stress

ObjectiveThe release of adipose tissue-derived miRNAs is increased under conditions of obesity, but the exact molecular mechanisms involved have not been elucidated. This study investigated whether obesity-induced increases in palmitic acid (PA) content could activate the NF-κB/endoplasmic reticulum stress (ER stress) pathway and promote the expression and release of exosomal miRNAs in adipocytes.MethodsAbdominal adipose tissue and serum samples were collected from normal weight individuals and people with obesity to clarify the correlation of serum PA content with NF-κB/ER stress and the release of exosomal miRNAs. NF-κB and ER stress were blocked in obese mice and in vitro cultured adipocytes to demonstrate the molecular mechanisms by which PA promotes the release of exosomal miRNAs.The morphology, particle size and distribution of the exosomes were observed via transmission electron microscopy and NTA.ResultsAccompanied by increased serum PA levels, the NF-κB/ER stress pathway was activated in the adipose tissue of people with obesity and in high-fat diet (HFD)-induced obese mice; moreover, the levels of miRNAs in both adipose tissue and serum were increased. P-p65 (Bay11-7082) and ER stress (TUDCA) blockers significantly reduced the levels of miRNAs in abdominal adipose tissue and serum, decreased blood glucose levels, and improved glucose tolerance and insulin sensitivity in obese mice. In 3T3-L1 adipocytes, high concentrations of PA activated the NF-κB/ER stress pathway and increased the expression and release of miRNAs in exosomes. P-p65 (Bay11-7082) and ER stress (TUDCA) blockers significantly reversed the increased release exosomal miRNAs cause by PA.ConclusionsObesity-induced increases in PA content increase the expression and release of miRNAs in adipocyte exosomes by activating the NF-κB/ER stress pathway.

Formulation of Natural Food Coloring Granules from Dragon Fruit Peel Extract (Hylocereus polyrhizus) and Effectiveness Test in Reducing Blood Glucose Levels

Anthocyanin is one of the many compounds in dragon fruit skin that can be used as an antioxidant. Dragon fruit skin can also lower blood glucose levels. The fact that cases of diabetes mellitus are increasing every year shows that this disease needs serious treatment. This study aims to make dragon fruit skin extract formulated in the form of granules and make dragon fruit skin extract granules that meet the requirements as natural food coloring and to determine the content and effectiveness of dragon fruit skin extract (Hylocereus polyrhizus) which can lower blood glucose levels. This research method is experimental. The One Way Anova test and the Tukey HSD post-hoc test were used to analyze the data. The outcomes showed that there were 9 granule recipes that met the assessment test necessities. After being induced by 20% fructose solution, the glucose level study revealed that the treatment of dragon fruit skin extract at 100, 200, and 400 mg / kgBW was able to lower blood glucose levels in test animals. Winged serpent natural product skin concentrate can be formed as granules. Equations 2 and 3 produce the best tone. The consequences of the review reasoned that winged serpent natural product skin remove (Hylocereus polyrhizus) at dosages of 100, 200 and 400 mg/kgBW was viable in decreasing blood glucose levels in guinea pigs prompted by 20% fructose arrangement and a portion of 200 mg/kgBW gave an impact of lessening blood glucose levels that was practically equivalent to the positive control.

Epicatechin and β-Glucan from Whole Highland Barley Grain Synergistic Benefit on Attenuating Hyperglycemia via Improving Hepatic Glucose Metabolism in Diabetic C57BL/6J Mice.

Our previous study proved that epicatechin (EC) and β-glucan (BG) from whole-grain highland barley synergistically modulate glucose metabolism in insulin-resistant HepG2 cells. However, the main target and the mechanism underlying the modulation of glucose metabolism in vivo remain largely unknown. In this study, cell transfection assay and microscale thermophoresis analysis revealed that EC and BG could directly bind to the insulin receptor (IR) and mammalian receptor for rapamycin (mTOR), respectively. Molecular dynamic analysis indicated that the key amino acids of binding sites were Asp, Met, Val, Lys, Ser, and Tys. EC supplementation upregulated the IRS-1/PI3K/Akt pathway, while BG upregulated the mTOR/Akt pathway. Notably, supplementation with EC + BG significantly increased Akt and glucose transporter type 4 (GLUT4) protein expressions, while decreasing glycogen synthase kinase 3β (GSK-3β) expression in liver cells as compared to the individual effects of EC and BG, indicating their synergistic effect on improving hepatic glucose uptake and glycogen synthesis. Consistently, supplementation with EC + BG significantly decreased blood glucose levels and improved oral glucose tolerance compared to EC and BG. Therefore, combined supplementation with EC and BG may bind to corresponding receptors, targeting synergistic activation of Akt expression, leading to the improvement of hepatic glucose metabolism and thereby ameliorating hyperglycemia in vivo.

Hyaluronate functionalized Span-Labrasol nanovesicular transdermal therapeutic system of ferulic acid targeting diabetic nephropathy

Diabetic kidney disease, known as diabetic nephropathy (DN), is a widespread severe diabetes complication leading to kidney failure. Due to the lack of efficacious therapies, this study endeavors to enhance DN therapeutic effectiveness of ferulic acid (FRA), a natural phenolic with poor oral bioavailability, by developing a transdermal kidney-targeted spanlastic formulation. Spanlastics (SP) nanovesicles were prepared using Span 60 and Labrasol or Brij35 as edge activators (EA). Cationic guar (CG) and hyaluronic acid (HA) were employed as coatings. The formulations were assessed for entrapment efficiency (EE), particle size (PS) and zeta potential (ZP). A 21 × 31 factorial optimization of FRA spanlastic formulations revealed the desirable nanoformula was FRA-L-H-SP comprising Labrasol and hyaluronate coating. Transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR), Diphenylpicrylhydrazyl (DPPH) antioxidant activity, in-vitro release, and rat skin ex-vivo permeation assessed this formula and the uncoated one (FRA-L-SP). Biochemical indicators and histopathology for diabetes and kidney injury were evaluated in the Streptozotocin (STZ)-induced DN rat model. Results showed significant improvements after treatment with FRA-L-H-SP compared to FRA-L-SP and free FRA, with decreased blood glucose, creatinine, and intercellular adhesion molecule-1 (ICAM-1) levels and increased insulin, AMP-activated protein kinase (AMPK), and sirtuins (SIRT). This enhancement can be acknowledged as passive targeting of SP and active targeting properties of hyaluronic to cluster of differentiation 44 (CD44) receptors, revealing the potential to improve DN pathophysiology.

Impact of Bitter Gourd (Momordica charantia) Hypoglycemic Formulation on Biochemical Parameters in Alloxan-induced Diabetic Albino Rats

Introduction: Diabetes mellitus is a widespread endocrine disorder that leads to chronic hyperglycemia, posing significant health challenges globally. Effective management of blood glucose levels remains a critical goal in diabetes treatment. Recent studies have highlighted the potential of natural products in diabetes management. Momordica charantia, commonly known as bitter gourd, has been traditionally used for its purported hypoglycemic effects. This study aims to evaluate the efficacy of a methanolic extract of Momordica charantia in reducing blood glucose levels in an animal model of diabetes and compare its effectiveness to a standard antidiabetic medication, Glizid-M. Materials and Methods: The study utilized alloxan-induced diabetic albino rats to assess the hypoglycemic effects of the methanolic extract of Momordica charantia. Diabetic rats were divided into groups and administered varying doses of the extract: 150 mg/kg, 300 mg/kg, and 600 mg/kg. A control group received Glizid-M, and a baseline group received no treatment. Blood glucose levels were monitored at regular intervals to evaluate the efficacy of the extract in managing hyperglycemia. Results and Discussion: The administration of the methanolic extract of Momordica charantia resulted in a dose-dependent reduction in blood glucose levels. Among the tested dosages, the 600 mg/kg dose demonstrated a statistically significant decrease in blood glucose compared to the lower doses of 150 mg/kg and 300 mg/kg. The 600 mg/kg dosage showed comparable efficacy to the standard antidiabetic drug, Glizid-M, indicating a strong hypoglycemic effect. The results of this study suggest that Momordica charantia has a potent hypoglycemic effect, with its efficacy increasing with dosage. The significant reduction in blood glucose levels at the highest dosage implies that the extract may influence glucose metabolism effectively. The dose-dependent response highlights the importance of optimizing dosage for maximum therapeutic benefit. Comparison with Glizid-M further supports the potential of Momordica charantia as a viable alternative or complementary therapy in diabetes management. Conclusion: This study provides scientific validation for the use of Momordica charantia methanolic extract as a therapeutic agent for diabetes management. The observed dose-dependent reduction in blood glucose levels suggests its potential as an effective natural remedy for controlling hyperglycemia. Further research is warranted to explore the underlying mechanisms and long-term efficacy of this extract in diabetes treatment.

Evaluation of cadmium effects on the glucose metabolism on insulin resistance HepG2 cells

Cadmium (Cd) is an environmental endocrine disruptor. Despite increasing research about the metabolic effects of Cd on HepG2 cells, information about the metabolic effects of Cd on insulin resistance HepG2 (IR-HepG2) cells is limited. Currently, most individuals with diabetes are exposed to Cd due to pollution. Previously, we reported that Cd exposure resulted in decreased blood glucose levels in diabetic mice, the underlying mechanism deserves further study. Therefore, we used palmitic acid (0.25 mM) to treat HepG2 cells to establish IR-HepG2 model. IR-HepG2 cells were exposed to CdCl2 (1 μM and 2 μM). Commercial kits were used to measure glucose production, glucose consumption, ROS and mitochondrial membrane potential. Western blot and qRT-PCR were used to measure the proteins and genes of glucose metabolism. In the current study setting, we found no significant changes in glucose metabolism in Cd-exposed HepG2 cells, but Cd enhanced glucose uptake, inhibited gluconeogenesis and activated the insulin signaling pathway in IR-HepG2 cells. Meanwhile, we observed that Cd caused oxidative stress and increased the intracellular calcium concentration and inhibited mitochondrial membrane potential in IR-HepG2 cells. Cd compensatingly increased glycolysis in IR-HepG2 cells. Collectively, we found Cd ameliorated glucose metabolism disorders in IR-HepG2 cells. Furthermore, Cd exacerbated mitochondrial damage and compensatory increased glycolysis in IR-HepG2 cells. These findings will provide novel insights for Cd exposure in insulin resistant individuals.

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.

SGLT-2 Inhibitors: The Next-generation Treatment for Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) has become a worldwide concern in recent years, primarily in highly developed Western societies. T2DM causes systemic complications, such as atherosclerotic heart disease, ischemic stroke, peripheral artery disease, kidney failure, and diabetes-related maculopathy and retinopathy. The growing number of T2DM patients and the treatment of long-term T2DM-related complications pressurize and exhaust public healthcare systems. As a result, strategies for combating T2DM and developing novel drugs are critical global public health requirements. Aside from preventive measures, which are still the most effective way to prevent T2DM, novel and highly effective therapies are emerging. In the spotlight of next-generation T2DM treatment, sodium-glucose co-transporter 2 (SGLT-2) inhibitors are promoted as the most efficient perspective therapy. SGLT-2 inhibitors (SGLT2i) include phlorizin derivatives, such as canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. SGLT-2, along with SGLT-1, is a member of the SGLT family of proteins that play a role in glucose absorption via active transport mediated by Na+/K+ ATPase. SGLT-2 is only found in the kidney, specifically the proximal tubule, and is responsible for more than 90% glucose absorption. Inhibition of SGLT-2 reduces glucose absorption, and consequently increases urinary glucose excretion, decreasing blood glucose levels. Thus, the inhibition of SGLT-2 activity ultimately alleviates T2DM-related symptoms and prevents or delays systemic T2DM-associated chronic complications. This review aimed to provide a more detailed understanding of the effects of SGLT2i responsible for the acute improvement in blood glucose regulation, a prerequisite for T2DM-associated cardiovascular complications control.

Potential Antihyperglycemic Effects of Adzuki (Vigna angularis) Polyphenols on Mice and Caco-2 Cells

Background/Purpose Some health-beneficial foods, including adzuki beans ( Vigna angularis), can show antihyperglycemic effects. Adzuki bean-derived polyphenols, such as (+)-catechin 7- O- β-d-glucopyranoside (C7G) and (+)-epicatechin 7- O- β-d-glucopyranoside (E7G), could be potential inhibitors of α-amylase and α-glucosidase, however, few studies of the activity of adzuki polyphenols have been performed in vivo. Thus, we evaluated the antihyperglycemic effects of crude adzuki bean extract containing polyphenols (ABP), and purified C7G or E7G using mice and Caco-2 cells. Methods Six-week-old male ICR mice were orally administered ABP (100 or 250 mg/kg), C7G or E7G (15 or 40 mg/kg), and sucrose (2 g/kg). Blood samples were taken from the lateral tail vein to measure the blood glucose levels at various times over 0–120 min. Cultured caco-2 cells, an intestinal model, were treated with ABP, C7G, or E7G. The glucose concentration in the medium was measured to examine the activity of α-glucosidase. Results Administration of adzuki polyphenols decreased blood glucose levels, especially E7G administration significantly showed antihyperglycemic effects in vivo. In Caco-2 cells, α-glucosidase activity was significantly decreased by ABP, C7G, or E7G addition in a dose-dependent manner without cytotoxicity. Conclusion These results suggest that C7G and E7G in adzuki bean extract inhibited sucrose-degrading enzymes to elicit antihyperglycemic effects in vivo, which supports the results of previous studies using adzuki beans, and may contribute to health promotion.

Effects of postprandial exercise timing on blood glucose and fluctuations in patients with type 2 diabetes mellitus.

The aim of this study was to assess how moderate-intensity aerobic exercise performed 45 minutes and 90 minutes after a meal affects blood glucose levels and fluctuations in individuals diagnosed with type 2 diabetes mellitus (T2DM). Twenty-two patients with T2DM, who were solely receiving oral hypoglycemic medication, were enrolled and divided randomly into two categories: those exercising 45 minutes after a meal (45-minute postprandial exercise group) and those exercising 90 minutes post-meal (90-minute postprandial exercise group). Both groups engaged in a 30-minute session of moderate-intensity aerobic stationary bike exercise following breakfast. This aerobic exercise regimen consisted of two stages, with the groups switching exercise timings after the initial phase. Continuous glucose monitoring (CGM) was utilized to evaluate the blood glucose levels and fluctuations in the participants. After breakfast, both overall daily blood glucose levels and the area under the curve for blood glucose following breakfast were reduced in the 45-minute postprandial exercise group compared to the 90-minute postprandial exercise group. The 45-minute postprandial exercise group demonstrated greater time spent within the target glucose range and less time above the target range than the 90-minute postprandial exercise group. Additionally, measures such as standard deviation, mean amplitude of glycemic excursions, largest amplitude of glycemic excursions, and postprandial glucose excursion for breakfast, peak postprandial glucose levels, and duration of elevated glucose levels were all lower in the 45-minute postprandial exercise group compared to the 90-minute postprandial exercise group. Moderate-intensity aerobic exercise lasting 45 minutes after meals was found to be more efficient in decreasing blood glucose levels and minimizing fluctuations compared to exercising 90 minutes after meals in patients with T2DM. Additionally, it notably reduced the peak in blood glucose levels after meals.