Increased Insulin Sensitivity Research Articles

Spirulina versus metformin for controlling some insulin signaling pathway genes in induced polycystic ovary syndrome rat model

Polycystic ovary syndrome (PCOS) is a prevalent endocrinologic and gynecologic disorder that affects women of reproductive age; besides, insulin resistance (IR) occurs in 50–70 % of PCOS cases. Metformin (Met) is commonly prescribed for IR management; however, it does not affect IR with some gastrointestinal symptoms. Spirulina platensis (SP) is a blue-green alga that may increase insulin sensitivity. Therefore, our study aims to evaluate SP as an alternative treatment to Met for improving glucose homeostasis by assessing the expression of 11 crucial genes involved in the insulin signaling pathway. After induction of the PCOS model using dehydroepiandrosterone (DHEA) (60 mg/kg bwt) for 30 consecutive days, rats were allocated into six groups. Relative liver weight, glutamic pyruvic transaminase (GPT) serum levels, glutamic-oxaloacetic transaminase (GOT), and Insulin were determined. Furthermore, the gene expression of Ins1, Irs1, Pik3ca, Prkcz, Foxo1, Srebf1, Ppargc1a, Pklr, Gk, G6pc, and Pepck in the rat's liver tissue was determined using RT-PCR. Treatment of the PCOS control group with Met or SP revealed a decrease in all these parameters compared with the PCOS model. Additionally, we found a statistically significant difference in the expression of both the Gk and Prkcz genes. To summarize our study results, SP or Met supplementation to PCOS rats had almost the same effect on assessed relative liver weight, GOT, GPT, and insulin levels compared with PCOS control rats. If further studies confirm and detect more impact of SP on IR in PCOS, SP could be used instead of Met since the latter causes many side effects.

Insights into the Anti-Adipogenic and Anti-Inflammatory Potentialities of Probiotics against Obesity.

Functional foods with probiotics are safe and effective dietary supplements to improve overweight and obesity. Thus, altering the intestinal microflora may be an effective approach for controlling or preventing obesity. This review aims to summarize the experimental method used to study probiotics and obesity, and recent advances in probiotics against obesity. In particular, we focused on studies (in vitro and in vivo) that used probiotics to treat obesity and its associated comorbidities. Several in vitro and in vivo (animal and human clinical) studies conducted with different bacterial species/strains have reported that probiotics promote anti-obesity effects by suppressing the differentiation of pre-adipocytes through immune cell activation, maintaining the Th1/Th2 cytokine balance, altering the intestinal microbiota composition, reducing the lipid profile, and regulating energy metabolism. Most studies on probiotics and obesity have shown that probiotics are responsible for a notable reduction in weight gain and body mass index. It also increases the levels of anti-inflammatory adipokines and decreases those of pro-inflammatory adipokines in the blood, which are responsible for the regulation of glucose and fatty acid breakdown. Furthermore, probiotics effectively increase insulin sensitivity and decrease systemic inflammation. Taken together, the intestinal microbiota profile found in overweight individuals can be modified by probiotic supplementation which can create a promising environment for weight loss along enhancing levels of adiponectin and decreasing leptin, tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and transforming growth factor (TGF)-β on human health.

ZnPP-laden nanoparticles improve glucose homeostasis and chronic inflammation during obesity.

Chronic inflammation plays a pivotal role in the development of Type 2 diabetes mellitus (T2DM). Previous studies have shown that haem oxygenase-1 (HO-1) plays a proinflammatory role during metabolic stress, suggesting that HO-1 inhibition could be an effective strategy to treat T2DM. However, the application of HO-1 inhibitors is restricted due to solubility-limited bioavailability. In this study, we encapsulated the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP), within nanoparticles and investigated their role in regulating glucose homeostasis and chronic inflammation during obesity. We delivered DMSO-dissolved ZnPP (DMSO-ZnPP) and ZnPP-laden nanoparticles (Nano-ZnPP) to diet-induced obese male mice for 6weeks. Glucose and insulin tolerance tests were carried out, liver and adipose tissue gene expression profiles analysed, and systemic inflammation analysed using flow cytometry. Nanoparticles significantly increased the delivery efficiency of ZnPP in both cells and mice. In mice with diet-induced obesity, inhibition of HO-1 by Nano-ZnPP significantly decreased adiposity, increased insulin sensitivity, and improved glucose tolerance. Moreover, Nano-ZnPP treatment attenuated both local and systemic inflammatory levels during obesity. Mechanistically, Nano-ZnPP significantly attenuated glucagon, TNF, and fatty acid synthesis signalling pathways in the liver. In white adipose tissue, the oxidative phosphorylation signalling pathway was enhanced and the inflammation signalling pathway diminished by Nano-ZnPP. Our results show that Nano-ZnPP has better effects on the improvement of glucose homeostasis and attenuation of chronic inflammation, than those of DMSO-dissolved ZnPP. These findings indicate that ZnPP-laden nanoparticles are potential therapeutic agents for treating T2DM.

Two-Month Consumption of Orange Juice Enriched with Vitamin D3 and Probiotics Decreases Body Weight, Insulin Resistance, Blood Lipids, and Arterial Blood Pressure in High-Cardiometabolic-Risk Patients on a Westernized Type Diet: Results from a Randomized Clinical Trial.

This study examined the effects of orange juice (OJ) supplemented with vitamin D3 (2000 IU) and probiotics (Lacticaseibacillus casei Shirota and Lacticaseibacillus rhamnosus GG, 108 cfu/mL) on cardiometabolic risk factors in overweight and obese adults following a Westernized-type diet. Fifty-three high-risk individuals were randomly assigned to one of two groups. Over 8 weeks, one group consumed a vitamin D3 and probiotic-enriched OJ and the other regular OJ (control). Diets remained unchanged and were documented through food diaries. Measures of metabolic and inflammatory markers and blood pressure were measured at the start and end of the study. Post-intervention, the enriched OJ group showed the following significant metabolic improvements (without changes in triglycerides, inflammation, or central blood pressure): reduced fasting insulin, peripheral blood pressure, body weight (-1.4 kg 95% CI: -2.4, -0.4), energy (-270 kcal 95% CI: -553.2, -13.7), macronutrient (dietary fat -238 kcal 95% CI: -11.9, -1.0; carbohydrates -155 kcal 95% CI: -282.4, -27.3; sugars -16.1 g 95% CI: -11.9, -1.0) intake, and better lipid profiles (total cholesterol -10.3 mg/dL 95% CI: -21.4, 0.9; LDL-C -7 mg/dL 95% CI: -13.5, -0.5). The enriched OJ led to weight loss, less energy/macronutrient consumption, improved lipid profiles, and increased insulin sensitivity after 8 weeks in those following a Westernized diet, thus indicating potential benefits for cardiometabolic risk. This study was a part of FunJuice-T2EDK-01922, which was funded by the EU Regional Development Fund and Greek National Resources.

Effect of high dietary fiber intake on insulin resistance, body composition and weight, among overweight or obese middle-aged women: study protocol for a double-blinded randomized controlled trail.

Background Obesity is a major consequence of malnutrition and significantly contributes to the global burden of chronic diseases. Currently, there are more overweight and obese individuals than underweight individuals. Increased fiber intake can increase insulin sensitivity and fat oxidation. According to research studies, the average dietary fiber consumption is below the recommended value, and the WHO anticipates that the worldwide obesity prevalence has increased in the past ten years. Aim To evaluate the effect of high dietary fiber intake on insulin resistance, body composition, and weight in overweight and obese middle-aged women. Method This hospital-based study evaluated 500 people during phase 1 to identify the prevalence of insulin resistance among overweight and obese middle-aged women. An RCT with intervention and control arms for 180 individuals is being conducted in Phase 2 to determine the effect of increased dietary fiber consumption on insulin resistance, body composition, and weight in overweight or obese middle-aged women. In the intervention group, women were counselled for 15 min and given a tailored food chart including 40 g of fiber. Women in the control arm will receive a typical food care plan with 25 g of fiber, based on their health status. Each engaged woman received fiber nutritional empowerment. Discussion Increasing dietary fiber consumption can improve insulin resistance, body composition, and weight in middle-aged overweight and obese women. Trial registration The Clinical Trials Registry of India (CTRI/2022/01/039074) has registered this study as a clinical trial on January 3, 2022 http://ctri.nic.in

Impaired Fibroblast Growth Factor 21 (FGF21) Associated with Visceral Adiposity Leads to Insulin Resistance: The Core Defect in Diabetes Mellitus.

The Central nervous system (CNS) is the prime regulator of signaling pathways whose function includes regulation of food intake (consumption), energy expenditure, and other metabolic responses like glycolysis, gluconeogenesis, fatty acid oxidation, and thermogenesis that have been implicated in chronic inflammatory disorders. Type 2 diabetes mellitus (T2DM) and obesity are two metabolic disorders that are linked together and have become an epidemic worldwide, thus raising significant public health concerns. Fibroblast growth factor 21 (FGF21) is an endocrine hormone with pleiotropic metabolic effects that increase insulin sensitivity and energy expenditure by elevating thermogenesis in brown or beige adipocytes, thus reducing body weight and sugar intake. In contrast, during starvation conditions, FGF21 induces its expression in the liver to initiate glucose homeostasis. Insulin resistance is one of the main anomalies caused by impaired FGF21 signaling, which also causes abnormal regulation of other signaling pathways. Tumor necrosis factor alpha (TNF-α), the cytokine released by adipocytes and inflammatory cells in response to chronic inflammation, is regarded major factor that reduces the expression of FGF21 and modulates underlying insulin resistance that causes imbalanced glucose homeostasis. This review aims to shed light on the mechanisms underlying the development of insulin resistance in obese individuals as well as the fundamental flaw in type 2 diabetes, which is malfunctioning obese adipose tissue.

Adipose tissue macrophages secrete small extracellular vesicles that mediate rosiglitazone-induced insulin sensitization.

The obesity epidemic continues to worsen worldwide, driving metabolic and chronic inflammatory diseases. Thiazolidinediones, such as rosiglitazone (Rosi), are PPARγ agonists that promote 'M2-like' adipose tissue macrophage (ATM) polarization and cause insulin sensitization. As ATM-derived small extracellular vesicles (ATM-sEVs) from lean mice are known to increase insulin sensitivity, we assessed the metabolic effects of ATM-sEVs from Rosi-treated obese male mice (Rosi-ATM-sEVs). Here we show that Rosi leads to improved glucose and insulin tolerance, transcriptional repolarization of ATMs and increased sEV secretion. Administration of Rosi-ATM-sEVs rescues obesity-induced glucose intolerance and insulin sensitivity in vivo without the known thiazolidinedione-induced adverse effects of weight gain or haemodilution. Rosi-ATM-sEVs directly increase insulin sensitivity in adipocytes, myotubes and primary mouse and human hepatocytes. Additionally, we demonstrate that the miRNAs within Rosi-ATM-sEVs, primarily miR-690, are responsible for these beneficial metabolic effects. Thus, using ATM-sEVs with specific miRNAs may provide a therapeutic path to induce insulin sensitization.

Metformin: Past, Present, and Future.

This review provides the most recent update of metformin, a biguanide oral antihyperglycemic drug used as a first-line treatment in type 2 diabetes mellitus. Metformin continues to dominate in the world of antidiabetics, and its use will continue to rise because of its high efficiency and easy availability. Apart from type 2 diabetes, research is exploring its potential in other conditions such as cancer, memory loss, bone disorders, immunological diseases, and aging. Metformin is the most prescribed oral antidiabetic worldwide. It has been in practical use for the last six decades and continues to be the preferred drug for newly diagnosed type 2 diabetes mellitus. It reduces glucose levels by decreasing hepatic glucose production, reducing intestinal glucose absorption, and increasing insulin sensitivity. It can be used as monotherapy or combined with other antidiabetics like sulfonylureas, DPP-4 inhibitors, SGLT-2 inhibitors, or insulin, improving its efficacy. Metformin can be used once or twice daily, depending on requirements. Prolonged usage of metformin may lead to abdominal discomfort, deficiency of Vitamin B12, or lactic acidosis. It should be used carefully in patients with renal impairment. Recent studies have explored additional benefits of metformin in polycystic ovarian disease, gestational diabetes mellitus, cognitive disorders, and immunological diseases. However, more extensive studies are needed to confirm these additional benefits.

Leaf extracts of Euclea natalensis A.D.C ameliorate biochemical abnormalities in high-fat-low streptozotocin-induced diabetic rats through modulation of the AMPK-GLUT4 pathway

ABSTRACT Euclea natalensis is a commonly used plant in traditional African medicine for treating several diseases, including diabetes. The objective of the present study was to evaluate the antidiabetic effects of the leaf extracts of Euclea natalensis and elucidate some of its mechanisms of action. High-fat diet – low Streptozotocin-induced diabetic Sprague Dawley rats were orally treated with the methanol and dichloromethane extracts (100 and 200 mg/kg bw), and their fasting blood glucose levels, body weights, and food and water intake were measured every seven days for 21 days. Biomarkers of oxidative stress, lipid profile, gluconeogenic enzyme activities, glucose transporter 4 (GLUT 4) protein expression, and AMP-activated protein kinase (AMPK) gene expression were also determined. The 200 mg/kg bw of methanol extracts significantly reduced fasting plasma glucose, glycated hemoglobin (HbAc1), triglycerides, and low-density lipoprotein levels. The extract increased insulin sensitivity and hepatic glycogen synthesis, decreased hepatic glucose output, and increased the activities of antioxidant enzymes in diabetic animals after 21 days of treatment. The methanol extract also significantly upregulated the relative expression of GLUT 4 protein via the promoted expression of skeletal muscle and hepatic AMPK. Histological investigation showed ameliorated pancreatic degeneration and expedited regeneration of islets of Langerhans in diabetic rats treated with the methanol extract compared with the dichloromethane extract. The findings demonstrated that Euclea natalensis has beneficial effects on the biochemical and cell abnormalities of type 2 diabetes, partly via the modulation of the AMPK – GLUT 4 pathway.

Anti-Diabetic Activity of an Extract of Syzygium Jambolanum – A Review

Syzygium jambolanum is a promising natural treatment for diabetes. The potential benefits of S jambolanum for diabetes include lowering blood sugar levels, increasing insulin sensitivity, protecting pancreatic beta cells, and slowing the absorption of glucose into the bloodstream. The anti-diabetic activity of the crude extract of S jambolanum was evaluated in L6 myotubes and the lipid deposition in tissue was measured using Nile red Staining. Nile red staining confirmed that a considerable quantity of lipids had been deposited in the tissue treated with a crude extract of S jambolanum, comparable to the quantity of lipids deposited with a standard drug known as Rosiglitazone. This study analyzed the anti-diabetic activity of a crude extract of S jambolanum to understand its potential as a feedstock for extracting bioactive constituents to screen for bioactive molecules in the treatment of diabetes.

Molecular Adaptation of Cardiac Remodeling in Metabolic Syndrome: Focus on AMPK, SIRT1 and PGC-1a

Obesity, lack of physical activity, and genetic predisposition might play a pivotal role in pathogenesis of metabolic syndrome. Cardiac function alteration including hemodynamic changes, contractility function, arrhythmia, and cellular respiratory function, might happen due to chronic condition in metabolic syndrome. Insulin resistance, neurohormonal activation and chronic inflammation might contribute to these changes. Cardiomyocyte had capabilities to adapt from these abnormalities, one of them is the activation of cellular pathway to resist cardiac injury from metabolic syndrome. This molecular pathway involves three proteins, including AMP-activated protein kinase (AMPK), sirtuin-1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator-α (PGC-1α). The aim of this narrative review is to elucidate role of AMPK, SIRT1, and PGC-1α in cardiac adaptation against cardiac dysfunction in metabolic syndrome. AMPK, SIRT-1, and PGC-1α contribute to adapt and to repair the cardiac injury resulting from celullar and mechanical stress from metabolic syndrome and prevent cardiac remodeling event. Several pathological events, such as insulin resistance, induce alteration of switching energy fuel to the heart, causing cardiomyocte to rely on glucose metabolism and lipotoxicity, leading to damages of cardiomyocyte through reactive oxygen species (ROS) generation and lipid peroxidation. Increase of ROS promotes cardiac injury followed by necrotic and apoptotic events. AMPK, SIRT1, and PGC-1α act as cardioprotector molecule against metabolic syndrome insults to several mechanism such as: AMPK play role as counter act of lipotoxicity and insulin resistance through increasing insulin sensitivity and regulate redox reaction. SIRT1 plays role in regulating apoptotic genes and PGC-1α repairs cardiac fuel sources. Activation of AMPK/SIRT1/PGC-1α prevent cardiac remodeling due to metabolic syndrome by increasing insulin sensitivity, increases mitochondrial biogenesis and reduce pro-apoptotic signals in cardiomyocte.Keywords: AMPK/SIRT1/PGC-α, cardiac remodeling, metabolic syndrome

A genetic mouse model of lean-NAFLD unveils sexual dimorphism in the liver-heart axis

Lean patients with NAFLD may develop cardiac complications independently of pre-existent metabolic disruptions and comorbidities. To address the underlying mechanisms independent of the development of obesity, we used a murine model of hepatic mitochondrial deficiency. The liver-heart axis was studied as these mice develop microvesicular steatosis without obesity. Our results unveil a sex-dependent phenotypic remodeling beyond liver damage. Males, more than females, show fasting hypoglycemia and increased insulin sensitivity. They exhibit diastolic dysfunction, remodeling of the circulating lipoproteins and cardiac lipidome. Conversely, females do not manifest cardiac dysfunction but exhibit cardiometabolic impairments supported by impaired mitochondrial integrity and β-oxidation, remodeling of circulating lipoproteins and intracardiac accumulation of deleterious triglycerides. This study underscores metabolic defects in the liver resulting in significant sex-dependent cardiac abnormalities independent of obesity. This experimental model may prove useful to better understand the sex-related variability, notably in the heart, involved in the progression of lean-NAFLD.

Glycomacropeptide as an Efficient Agent to Fight Pathophysiological Mechanisms of Metabolic Syndrome.

There is currently a growing interest in the use of nutraceuticals as a means of preventing the development of complex diseases. Given the considerable health potential of milk-derived peptides, the aim of this study was to investigate the protective effects of glycomacropeptide (GMP) on metabolic syndrome. Particular emphasis was placed on the potential mechanisms mitigating cardiometabolic disorders in high-fat, high-fructose diet-fed mice in the presence of GMP or Bipro, an isocaloric control. The administration of GMP for 12 weeks reduced obesity, hyperglycemia and hyperinsulinemia caused by a high-fat, high-fructose diet, resulting in a decline in insulin resistance. GMP also lessened systemic inflammation, as indicated by decreased circulating inflammatory cytokines. In the intestinal and hepatic tissues, GMP improved homeostasis by increasing insulin sensitivity and attenuating high-fat, high-fructose-induced inflammation, oxidative stress and endoplasmic reticulum stress. Biochemical and histological analyses revealed improved hepatic steatosis and fatty acid composition in the livers of high-fat, high-fructose diet-fed mice treated with GMP compared to Bipro. A trend toward a decrease in bile acids without any marked changes in intestinal microbiota composition characterized GMP-treated animals compared to those administered Bipro. GMP offers considerable potential for fighting metabolic syndrome-related components and complications given its beneficial effects on risk factors such as inflammation, oxidative stress and endoplasmic reticulum stress without involving the intestinal microbiota.

Renal effects of GLP-1 receptor agonists and tirzepatide in individuals with type 2 diabetes: seeds of a promising future.

Chronic kidney disease (CKD) is one of the most common complications of type 2 diabetes (T2D), and CKD-related disability and mortality are increasing despite the recent advances in diabetes management. The dual GIP/GLP-1 receptor agonist tirzepatide is among the furthest developed multi-agonists for diabetes care and has so far displayed promising nephroprotective effects. This review aims to summarize the evidence regarding the nephroprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RA) and tirzepatide and the putative mechanisms underlying the favorable renal profile of tirzepatide. A comprehensive literature search was performed from inception to July 31st 2023 to select research papers addressing the renal effects of GLP-1RA and tirzepatide. The pathogenesis of CKD in patients with T2D likely involves many contributors besides hyperglycemia, such as hypertension, obesity, insulin resistance and glomerular atherosclerosis, exerting kidney damage through metabolic, fibrotic, inflammatory, and hemodynamic mechanisms. Tirzepatide displayed an unprecedented glucose and body weight lowering potential, presenting also with the ability to increase insulin sensitivity, reduce systolic blood pressure and inflammation and ameliorate dyslipidemia, particularly by reducing triglycerides levels. Tirzepatide is likely to counteract most of the pathogenetic factors contributing to CKD in T2D, potentially representing a step forward in incretin-based therapy towards nephroprotection. Further evidence is needed to understand its role in renal hemodynamics, fibrosis, cell damage and atherosclerosis, as well as to conclusively show reduction of hard renal outcomes.

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

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

Anti-diabetic effect of anthocyanin cyanidin-3-O-glucoside: data from insulin resistant hepatocyte and diabetic mouse

BackgroundAnthocyanins are a group of natural products widely found in plants. They have been found to alleviate the disorders of glucose metabolism in type 2 diabetes mellitus (T2DM), while the underlying mechanisms remain unclear.MethodsHepG2 and L02 cells were incubated with 0.2 mM PA and 30 mM glucose for 24 h to induce IR, and cells treated with 5 mM glucose were used as the control. C57BL/6 J male mice and db/db male mice were fed with a chow diet and gavaged with pure water or cyanidin-3-O-glucoside (C3G) solution (150 mg/kg/day) for 6 weeks.ResultsIn this study, the anthocyanin C3G, extracted from red bayberry, was found to alleviate disorders of glucose metabolism, which resulted in increased insulin sensitivity in hepatocytes, and achieved by enhancing the glucose consumption as well as glycogen synthesis in insulin resistance (IR) hepatpcytes. Subsequently, the expression of key proteins involved in IR was detected by western blotting analysis. Protein tyrosine phosphatase-1B (PTP1B), a negative regulator of insulin signaling, could reduce cellular sensitivity to insulin by inhibiting the phosphorylation of insulin receptor substrate-2 (IRS-2). Results of this study showed that C3G inhibited the increase in PTP1B after high glucose and palmitic acid treatment. And this inhibition was accompanied by increased phosphorylation of IRS proteins. Furthermore, the effect of C3G on improving IR in vivo was validated by using a diabetic db/db mouse model.ConclusionThese findings demonstrated that C3G could alleviate IR in vitro and in vivo to increase insulin sensitivity, which may offer a new insight for regulating glucose metabolism during T2DM by using the natural dietary bioactive components.C3G promotes the phosphorylation of IRS-2 proteins by suppressing the expression of PTP1B, and then enhances the sensitivity of hepatocyte to insulin.

Blautia Coccoides is a Newly Identified Bacterium Increased by Leucine Deprivation and has a Novel Function in Improving Metabolic Disorders.

Gut microbiota is linked to human metabolic diseases. The previous work showed that leucine deprivation improved metabolic dysfunction, but whether leucine deprivation alters certain specific species of bacterium that brings these benefits remains unclear. Here, this work finds that leucine deprivation alters gut microbiota composition, which is sufficient and necessary for the metabolic improvements induced by leucine deprivation. Among all the affected bacteria, B. coccoides is markedly increased in the feces of leucine-deprived mice. Moreover, gavage with B. coccoides improves insulin sensitivity and reduces body fat in high-fat diet (HFD) mice, and singly colonization of B. coccoides increases insulin sensitivity in gnotobiotic mice. The effects of B. coccoides are mediated by metabolizing tryptophan into indole-3-acetic acid (I3AA) that activates the aryl hydrocarbon receptor (AhR) in the liver. Finally, this work reveals that reduced fecal B. coccoides and I3AA levels are associated with the clinical metabolic syndrome. These findings suggest that B. coccoides is a newly identified bacterium increased by leucine deprivation, which improves metabolic disorders via metabolizing tryptophan into I3AA.

High-intensity interval training combining rowing and cycling improves but does not restore beta-cell function in type 2 diabetes.

We investigated whether a high-intensity interval training (HIIT)-protocol could restore beta-cell function in type 2 diabetes compared with sedentary obese and lean individuals. In patients with type 2 diabetes, and age-matched, glucose-tolerant obese and lean controls, we examined the effect of 8-weeks of supervised HIIT combining rowing and cycling on the acute (first-phase) and second-phase insulin responses, beta-cell function adjusted for insulin sensitivity (disposition index) and serum free fatty acid (FFA) levels using the Botnia clamp (1-h IVGTT followed by 3-h hyperinsulinemic-euglycemic clamp). At baseline, patients with type 2 diabetes had reduced insulin sensitivity (~40%), acute insulin secretion (~13-fold) and disposition index (>35-fold) whereas insulin-suppressed serum FFA was higher (⁓2.5-fold) compared with controls (all P<0.05). The HIIT-protocol increased insulin sensitivity in all groups (all P<0.01). In patients with type 2 diabetes, this was accompanied by a large (>200%) but variable improvement in the disposition index (P<0.05). Whereas insulin sensitivity improved to the degree seen in controls at baseline, the disposition index remained markedly lower in patients with type 2 diabetes after HIIT (all P<0.001). In controls, HIIT increased the disposition index by ~20-30% (all P<0.05). In all groups, the second-phase insulin responses and insulin-suppressed FFA levels were reduced in response to HIIT (all P<0.05). No group-differences were seen in these HIIT-induced responses. HIIT combining rowing and cycling induced a large but variable increase in beta-cell function adjusted for insulin sensitivity in type 2 diabetes, but the disposition index remained severely impaired compared to controls suggesting that this defect is less reversible in response to exercise training than insulin resistance.

Effect of Exercise Conditioning on Countering the Effects of Obesity and Insulin Resistance in Horses-A Review.

Obesity is an important health concern in horses, along with humans and companion animals. Adipose tissue is an inflammatory organ that alters the insulin-signaling cascade, ultimately causing insulin dysregulation and impaired glucose metabolism. These disruptions can increase the risk of metabolic disease and laminitis in horses and may also impact energy metabolism during exercise. A single bout of exercise, along with chronic exercise conditioning, increases insulin sensitivity and glucose disposal via both contraction- and insulin-mediated glucose uptake pathways. Regular exercise also increases calorie expenditure, which can facilitate weight (as body fat) loss. This paper explores the metabolic pathways affected by adiposity, as well as discusses the impact of exercise on insulin metabolism in horses.

Amphibian host-defense peptides with potential for Type 2 diabetes therapy – an updated review

Investigations conducted since 2018 have identified several host-defense peptides present in frog skin secretions whose properties suggest the possibility of their development into a new class of agent for Type 2 diabetes (T2D) therapy. Studies in vitro have described peptides that (a) stimulate insulin release from BRIN-BD11 clonal β-cells and isolated mouse islets, (b) display β-cell proliferative activity and protect against cytokine-mediated apoptosis and (c) stimulate production of the anti-inflammatory cytokine IL-10 and inhibit production of the pro-inflammatory cytokines TNF-α and IL-1β. Rhinophrynin-27, phylloseptin-3.2TR and temporin F are peptides with therapeutic potential. Studies in vivo carried out in db/db and high fat-fed mice have shown that twice-daily administration of [S4K]CPF-AM1 and [A14K]PGLa-AM1, analogs of peptides first isolated from the octoploid frog Xenopus amieti, over 28 days lowers circulating glucose and HbA1c concentrations, increases insulin sensitivity and improves glucose tolerance and lipid profile. Peptide treatment produced potentially beneficial changes in the expression of skeletal muscle genes involved in insulin signaling and islet genes involved in insulin secretion in these murine models of T2D. Lead compounds uncovered by the study of frog HDPs may provide a basis for the design of new types of agents that can be used, alone or in combination with existing therapies, for the treatment of T2D.