Insulin Resistance In Diabetic Rats Research Articles

Exercise ameliorates muscular excessive mitochondrial fission, insulin resistance and inflammation in diabetic rats via irisin/AMPK activation

This study aimed to investigate the effects of exercise on excessive mitochondrial fission, insulin resistance, and inflammation in the muscles of diabetic rats. The role of the irisin/AMPK pathway in regulating exercise effects was also determined. Thirty-two 8-week-old male Wistar rats were randomly divided into four groups (n = 8 per group): one control group (Con) and three experimental groups. Type 2 diabetes mellitus (T2DM) was induced in the experimental groups via a high-fat diet followed by a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 30 mg/kg body weight. After T2DM induction, groups were assigned as sedentary (DM), subjected to 8 weeks of treadmill exercise training (Ex), or exercise training combined with 8-week cycloRGDyk treatment (ExRg). Upon completion of the last training session, all rats were euthanized and samples of fasting blood and soleus muscle were collected for analysis using ELISA, immunofluorescence, RT-qPCR, and Western blotting. Statistical differences between groups were analyzed using one-way ANOVA, and differences between two groups were assessed using t-tests. Our findings demonstrate that exercise training markedly ameliorated hyperglycaemia, hyperlipidaemia, and insulin resistance in diabetic rats (p < 0.05). It also mitigated the disarranged morphology and inflammation of skeletal muscle associated with T2DM (p < 0.05). Crucially, exercise training suppressed muscular excessive mitochondrial fission in the soleus muscle of diabetic rats (p < 0.05), and enhanced irisin and p-AMPK levels significantly (p < 0.05). However, exercise-induced irisin and p-AMPK expression were inhibited by cycloRGDyk treatment (p < 0.05). Furthermore, the administration of CycloRGDyk blocked the effects of exercise training in reducing excessive mitochondrial fission and inflammation in the soleus muscle of diabetic rats, as well as the positive effects of exercise training on improving hyperlipidemia and insulin sensitivity in diabetic rats (p < 0.05). These results indicate that regular exercise training effectively ameliorates insulin resistance and glucolipid metabolic dysfunction, and reduces inflammation in skeletal muscle. These benefits are partially mediated by reductions in mitochondrial fission through the irisin/AMPK signalling pathway.

Molecular Approach to Identify Anti-inflammatory Potential of Stevioside in HFD-induced Type 2 Diabetic Rats: Evidence From in Vivo Study

Stevioside is a natural sweetener derived from the leaves of the Stevia rebaudiana plant. It has gained popularity as a sugar substitute due to its intense sweetness without adding calories or affecting blood sugar levels, making it a suitable option for people with diabetes or those looking to reduce their sugar intake. Studies have shown that stevioside has glucose lowering effects. Previous studies have shown that it has significant role in skeletal muscle but its role on expression of inflammatory signaling molecules in adipose tissue against high diet and sucrose-induced type-2 diabetes in experimental rats is yet to be done. The current research was undertaken to investigate if stevioside could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of stevioside (20 mg/kg b.wt) was administered orally for 45 days to high fat diet and sucrose induced type-2 diabetic rats. Interestingly, stevioside treatment restores the elevated serum levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α) and sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator–activated receptor-γ (PPAR-γ) in adipocytes of diabetic rats. The gene expression of IR, GLUT4 and PPAR-γ mRNA were also significantly activated in stevioside treated groups but reduced IL-1 beta, IlL-6, IKKB, TNF-alpha and NFkB mRNA expression in diabetic adipose tissue. More importantly, stevioside acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that stevioside inhibits obesity induced insulin resistance by ameliorating the inflammatory events and upregulating insulin signalling molecules. Keywords: Stevioside, HFD-T2DM, pro inflammation, insulin signalling; adipose tissue, obesity; signaling pathways; Therapautics.

Plantain flour – A beneficial material for the organ and transcriptional profile of kidney of diabetic rats

This study investigated the ameliorative effects of plantain flour on the organs of diabetic rats, and explored the mechanism from the perspective of kidney transcription. Diabetes was induced in rats by streptozotocin (STZ) and a high-sugar and high-fat diet. The alleviation effects and molecular mechanism of diabetes by plantain flour at different doses (1 g/kg·Bw, 2 g/kg·Bw, and 4 g /kg·Bw) were evaluated based on the analysis of biochemical indicators, histological observations, homeostasis model, and kidney transcriptome. The findings demonstrated that the intervention of plantain flour can reduce the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and urea (UREA). The pathological study revealed that plantain flour can alleviate the pathological symptoms of fat accumulation in liver and kidney tissue. According to the homeostasis model, plantain flour was able to reduce insulin resistance in diabetic rats. Transcriptome analysis showed that plantain flour improved dyslipidemia by up-regulating Acsl1, down-regulating Fabp4 and Plin1, and reduced kidney injury by up-regulating Slco1a6, Hsd17b2, Cyp2c24, and Cyp2c11 genes. These results suggested that plantain flour could improve the organ damage caused by diabetes and has the potential to be developed into healthy food.

Moderate and high-intensity interval training protect against diabetes-induced modulation of hepatic CD86 and CD206 expression associated with the amelioration of insulin resistance and inflammation in rats

Diabetes Mellitus (DM) can damage the function of metabolic tissues, including the liver. Liver macrophages are the first responders to tissue damage or exercise. We sought to determine whether eight weeks of interval training (HIIT & MIIT) protect against diabetes-induced modulation of hepatic CD86 and CD206 expression associated with the amelioration of insulin resistance and inflammation in rats. Thirty rats were divided into six groups, including a control group, MIIT, HIIT, DM, DM + MIIT, and DM + HIIT (n = 5 in each group). Diabetes was induced using a combination of a high-fat diet (HFD) and STZ. Wistar rats in the exercise groups were subjected to moderate and high-intensity interval training for eight weeks. After sample collection, liver tissue was removed and weighed. Serum levels of TNFα, IL-6, TGFβ, and IL-10 were measured by ELISA. Protein expression of the immune markers CD86 and CD206 in liver tissue was determined by immunohistochemical staining. Induction of diabetes increased glycemic indices, insulin resistance, and liver injury enzymes, especially in DM and DM + HIIT groups (p < 0.05). Moreover, diabetic groups showed an increase in liver CD86 protein expression, an increase in TNFα, IL-6, and TGFβ serum levels, and a decrease in liver CD206 and serum IL-10 (p < 0.05). Doing exercise while being diabetic, especially MIIT, significantly reversed the aforementioned factors and reduced insulin resistance (p < 0.05), except IL-10). We concluded that performing exercise training specially MIIT by decreasing CD86 and increasing CD206 in the liver, followed by decreasing pro-inflammatory factors (TNFα, IL-6) caused the regulation of liver enzymes and insulin resistance in diabetic rats. Therefore, it seems that exercise training by regulating macrophage markers CD86 and CD206 can reduce damage to the insulin-signaling pathway by reducing pro-inflammatory cytokines.

Fucus vesiculosus polysaccharide alleviates type 2 diabetes in rats via remodeling gut microbiota and regulating glycolipid metabolism-related gene expression

The antidiabetic activity and underlying mechanisms of Fucus vesiculosus polysaccharide (FVP) were studied in type 2 diabetic rats. Our results exhibited that FVP intervention reversed body weight loss, alleviated hyperglycemia and insulin resistance in diabetic rats. FVP also had the potential to ameliorate dyslipidemia, liver and kidney dysfunction, decrease oxidative stress, promote glycogen synthesis, and boost short-chain fatty acid production and total bile acid excretion. 16S rRNA gene sequencing analysis suggested that FVP interfered with the gut microbiota in a beneficial manner. Moreover, RT-qPCR results demonstrated that the antidiabetic activity of FVP in connection with the acceleration of blood glucose absorption and glycogen synthesis, the inhibition of gluconeogenesis, and the regulation of lipid metabolism in the liver. These findings suggested that FVP had antidiabetic effects on high-fat diet and STZ-induced diabetic rats and could be a potential resource for treating type 2 diabetes mellitus.

Study on Undercarboxylated Osteocalcin in Improving Cognitive Function of Rats with Type 2 Diabetes Mellitus by Regulating PI3K-AKT-GSK/3β Signaling Pathwaythrough medical images

ABSTRACT This paper aims to clarify the effect of Undercarboxylated osteocalcin (ucOC) on cognitive function in rats with type 2 diabetes mellitus (T2DM). This research reviewed the cognitive function of 35 diabetic patients, 33 non-diabetic patients and the serum levels of Undercarboxylated osteocalcin (ucOC) in patients. What’s more, we analyzed the correlation between serum ucOC levels and cognitive function. Diabetic rats were treated with high (30 μg·kg−1·d−1) and low (10 μg·kg−1·d−1) doses of ucOC to investigate its effects in regulating ucOC on blood lipid, blood glucose and cognitive function. We systematically detected the phosphorylation levels of cognitive level-related proteins (PI3K, AKT, and GSK/3β) in the hippocampus by Western Blot. Finally, PI3K-Akt pathway involved in regulating cognitive function in diabetic rats by ucOC was verified with AKT pathway inhibitor LY294002. MoCA score and serum ucOC levels were significantly reduced in patients with diabetes mellitus. ucOC could concentration-dose-dependently decrease the blood glucose and lipid levels, and improve glucose metabolism and weaken insulin resistance in diabetic rats (P < 0.001). In addition, escape latency in diabetic rats was significantly higher than that of normal rats in the Morris maze test, and ucOC dose-dependently shortened the escape latency in diabetic rats (all with P < 0.05). After using AKT pathway inhibitor, ucOC failed to shorten the escape latency in diabetic rats. In conclusion, this study explored the relevant mechanisms in inducing cognitive dysfunction of T2DM, suggesting the potential value of ucOC as a drug to improve cognitive dysfunction in patients with T2DM in clinical.

Red honeybush (Cyclopia genistoides) tea mitigates oxidative imbalance and hyperlipidemia, while improving glucose homeostasis in type 2 diabetic rats

Red honeybush tea (RHT) is a tea product developed from Cyclopia spp. which is endemic to South Africa. Aside refreshment, RHT has over the years been used traditionally in the treatment of various diseases including type 2 diabetes. This study investigated the in vivo antioxidant and anti-diabetic activity of RHT concentrated hot water extract in type 2 diabetes (T2D) model of rats. T2D was induced starting with feeding 10 % fructose solution ad libitum for 2 weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight (BW)). Five weeks of treatment of RHT led to significant (P < 0.05) elevation in serum insulin, pancreatic β-cell function, HDL-c levels with concomitant decrease in AST, ALT, ALP, urea, CK-MB, fructosamine, total cholesterol, triglycerides, LDL-c, and insulin resistance in diabetic rats. RHT also significantly (P < 0.05) decreased MDA levels and enhanced level of GSH, activity of SOD, catalase, GR in most of organs (pancreas, liver, kidneys, and heart). Significantly (P < 0.05) improved morphological changes in the islets and β-cells were observed in rats treated with RHT. The data of this study suggest that RHT demonstrates an outstanding antioxidant and anti-diabetic effects in STZ-induced T2D model of rats.

Effect of Aerobic Training with Aqueous Allium sativum L on IL-17, IL-22 Expression and Insulin Resistance in Diabetic Rats

زمینه و هدف: در حال حاضر شواهد فزاینده‌ای وجود دارد که نشان می‌دهد مسیرهای پیش‌التهابی که توسط سلول‌های T (که IL-17 و IL-22 را ترشح می‌کنند)، تعدیل می‌شوند، نقش مهمی در کنترل سوخت‌وسازی دارند. هدف از پژوهش حاضر بررسی اثر تمرین هوازی همراه با مصرف عصارة آبی سیر بر بیان IL-17، IL-22 و مقاومت‌ به ‌انسولین موش‌های صحرایی دیابتی با استرپتوزوتوسین است.مواد و روش‌ها: در این تحقیق تجربی،40 سر موش صحرایی نر (سن 5 هفته و وزن 24/15 ± 12/162 گرم) از نژاد ویستار از انستیتو پاستور تهیه و به آزمایشگاه منتقل شدند. پس از انتقال رت‌ها به آزمایشگاه، القای دیابت و آشنایی با فعالیت ورزشی روی نوار گردان ویژة جوندگان، به‌طور تصادفی به پنج گروه کنترل-سالم (CN)، دیابت (DM)، دیابت-تمرین (TDM)، دیابت-سیر (GDM) و دیابت-تمرین-سیر (TGDM) تقسیم شدند. القای دیابت با تزریق داخل‌صفاقی استرپتوزوتوسین به‌صورت تک‌دوز (mg/kg 60) انجام گرفت. قند خون 250 میلی‌گرم بر دسی‌لیتر، حاکی از دیابتی شدن موش‌ها بود. گروه‌های تمرین به مدت هشت هفته برنامة تمرین هوازی (10-18 متر در دقیقه، 10-40 دقیقه در روز، پنج روز در هفته) را روی نوار گردان انجام دادند. روزانه به ازای هر صد گرم وزن موش‌های صحرایی، یک میلی‌لیتر (حدود 4/0 گرم در هر 100 گرم وزن بدن) عصارة سیر گاواژ شد. بیان IL-17 و IL-22 به روش RT-PCR اندازه‌گیری شد. پس از برآورد میزان گلوکز و انسولین ناشتا، از شاخص HOMA-IR برای ارزیابی مقاومت به انسولین استفاده شد. داده‌ها با استفاده از آزمون آنوا و ضریب همبستگی پیرسون در سطح معناداری 05/0 P< بررسی شد.نتایج: بیان IL-17 (0001/0P=)، IL-22 (0001/0P=) و مقدار HOMA-IR (0001/0P=) در گروه‌های DM نسبت به گروه CN افزایش یافت. IL-17، IL-22 و HOMA-IR در گروه‌های TDM (به‌ترتیب 008/0P=، 040/0P=، 0001/0P=)، GDM (به‌ترتیب 017/0P=، 044/0P=، 0001/0P=) و TGDM (به‌ترتیب 0001/0P=، 0001/0P=، 0001/0P=) نسبت به گروه DM به‌طور معنادار کمتر بود. همچنین Il-17 و IL-22 در گروه TGDM نسبت به گروه TDM (به‌ترتیب 045/0P=، 041/0P=) و GDM (به‌ترتیب 023/0P=، 038/0P=) به‌طور معنادار کمتر بود. بین HOMA-IR با IL-17 (0001/0P=) و IL-22 (001/0P=) همبستگی مثبتی مشاهده شد.نتیجه‌گیری: یافته‌های پژوهش حاضر نشان می‌دهد که احتمالاً افزایش در میزان بیان نسبی IL-17 و IL-22 ناشی از القای دیابت با افزایش مقاومت به انسولین همراه است. کاهش بیان IL-17 و IL-22 بافت چربی در پی تمرین هوازی و عصارة آبی سیر با کاهش HOMA-IR در موش‌های دیابتی همراه بود. افزون‌بر این، ترکیب تمرین هوازی با عصاره سیر تأثیرات هم‌افزایی داشت و موجب کاهش التهاب و HOMA-IR نسبت به هر کدام به‌تنهایی شد. از آنجا که افراد دیابتی پیوسته در معرض التهاب هستند و با توجه به تغییرات IL-17 و IL-22 در پی فعالیت ورزشی هوازی و مصرف عصاره سیر، استفاده از این دو عامل احتمالاً می‌تواند اهمیت درمانی برای بیماران T2DM داشته باشد.

Effect of Rosuvastatin and Glibenclamide in Alone or in Combination on Glucose Homeostasis in Diabetic Male Albino Wistar Rats: An Observer-blinded Experimental Interventional Study

Introduction: Metabolic Syndrome (MetS) is a complex of metabolic disorders which include obesity, insulin resistance, hyperglycaemia, hypertension along with dyslipidemia. It is not clear whether rosuvastatin is having role in new onset diabetes. Aim: To assess the effect of rosuvastatin in comparison to glibenclamide on blood sugar levels and insulin resistance in diabetic rats. Materials and Methods: This experimental study was carried out at Sri Manakula Vinayagar Medical College and Hospital, Kalitheerthalkuppam, Puducherry on 42 adult male Wistar rats, for 8 weeks. Diabetes was created by feeding rats with High Fat and High Sugar (HFHS) diet over a period of 8 weeks. In total, 42 rats were allocated to in 7 groups, consisting of 6 animals per group. Group I -vehicle treated animals (control), group II - HFHS diet animals (Diabetic Control- DC), group III- glibenclimide (G) (5 mg/kg) + HFHS, group IV-rosuvastatin (R) (5 mg/kg) + HFHS, group V-R (10 mg/kg) + HFHS, group VI-G (5 mg/kg) + R (5 mg/kg) + HFHS diet, group VII-G (5 mg/kg) + R (10 mg/kg) + HFHS diet continued for 4 weeks. Rosuvastatin and glibenclamide were dissolved in distilled water and 95% ethanol respectively, and were given orally daily for 4 weeks after induction of diabetes. Data were subjected to one-way ANOVA using Statistical Package for the Social Sciences (SPSS) version 24.0 followed by non parametric test with significance level set for p-value&lt;0.05. Results: By end of 8th week, on comparison of control group with HFHS diet and glibenclamide treated group, there was significant rise in body weight, serum Low Density Lipoprotein (LDL), in addition to Very Low Density Lipoprotein (VLDL) and Triglycerides (TG) levels. Glibenclamide treated (group III) animals on comparison with groups IV, V, VI, VII revealed reduction in body weight, serum LDL, VLDL and TG levels (p &lt;0.001). Glibenclamide treated (group III) on comparing with groups IV, V, VI, VII, there was significant high serum HDL level (p&lt;0.001). By 8th week, significant decrease in serum insulin and HOMA-IR level was observed when glibenclamide group III was compared with groups IV to VII treated animals (p &lt;0.001). Conclusion: The study results indicate that the combination therapy of rosuvastatin and glibenclamide demonstrate beneficial effects on weight reduction, lipid profile and insulin resistant.

Effect of 4 Weeks of Progressive Resistance Training on Plasma Levels of Omentin-1 and Metabolic Factors in Diabetic Male Rats

Background and Objectives Omentin-1 is a new adipokine with a potential to increase insulin sensitivity, and is associated with lipid profile. There are limited studies on the effect of exercise on the serum level of Omentin-1. The present study aims to investigate the effect of progressive resistance training (PRT) on plasma level of omentin-1 and glycemic control in diabetic male rats. Subjects and Methods In this study, 24 male Wistar rats were randomly divided into three groups: Control, diabetic, and diabetic+PRT. The training group performed a PRT program using a ladder (three days a week, for 4 weeks). Body weight, glucose level, amentin-1 level, insulin level, and lipid profile were measured. Results The PRT significantly increased plasma levels of omentin-1 and triglycerides in the diabetic + PRT group compared to the diabetic group (P=0.017). There was no significant difference in high-density lipoprotein (F=0.318, P&gt;0.05), low-density lipoprotein (F=0.612, P&gt;0.05) and cholesterol (F=0.049, P&gt;0.05) levels between the study groups. Conclusion The PRT improves omentin-1 and insulin resistance in diabetic rats.

Metabonomics combined with 16S rRNA sequencing to elucidate the hypoglycemic effect of dietary fiber from tea residues

Tea residues are rich in dietary fiber, which possesses excellent physicochemical and functional properties in vitro. However, the hypoglycemic effect and mechanism of dietary fiber from tea residues are not clear. The study aimed to investigate the potential hypoglycemic effect of dietary fiber obtained from tea residues fermentation (TRDF) and reveal its related mechanisms of action in terms of both intestinal flora and metabolomics. The type 2 diabetes (T2D) rat model induced by high-fat diet and streptozotocin injection was applied in this study. Four weeks of TRDF intervention could remarkably ameliorate hyperglycemia, severe oxidative stress and insulin resistance of diabetic rats. Additionally, there was a significant increase of short chain fatty acids (SCFAs) concentrations in feces of diabetic rats after TRDF intervention. Furthermore, TRDF played a positive role in relieving intestinal microbiota dysbiosis by enriching beneficial bacteria (S24-7 and Prevotellaceae) and inhibiting harmful bacteria (Desulfovibrionaceae and Clostridiaceae). Metabolomic analysis showed that TRDF improved the amino acid metabolism and citrate cycle. The study elaborated on the hypoglycemic effect and potential mechanisms of TRDF through multiple pathways of gut microbiota and metabolites, which could provide theoretical basis for TRDF as a dietary supplement to manage T2D.

Luteolin loaded on zinc oxide nanoparticles ameliorates non-alcoholic fatty liver disease associated with insulin resistance in diabetic rats via regulation of PI3K/AKT/FoxO1 pathway.

Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem with high prevalence and morbidity associated with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), and dyslipidemia. Nano-formulation of luteolin with Zn oxide in the form of Lut/ZnO NPs may improve the anti-diabetic property of each alone and ameliorate the insulin resistance thus management of NAFLD. This study aimed to measure the efficiency of Lut/ZnO NPs against insulin resistance coupled with NAFLD and T2DM. A diabetic rat model with NAFLD was induced by a high-fat diet and streptozotocin (30mg/kg I.P). Serum diabetogenic markers levels, lipid profile, and activity of liver enzymes were measured beside liver oxidative stress markers. Moreover, the hepatic expressions of PI3K/AKT/FoxO1/SERBP1c as well as heme oxygenase-1 were measured beside the histopathological examination. Lut/ZnO NPs treatment effectively reduced hyperglycemia, hyperinsulinemia, and ameliorated insulin resistance. Additionally, Lut/ZnO NPs improved the hepatic functions, the antioxidant system, and reduced the oxidative stress markers. Furthermore, the lipid load in the liver, as well as the circulating TG and TC, was minified via the suppression of lipogenesis and gluconeogenesis. Moreover, Lut/ZnO NPs activated the PI3K/AKT signaling pathway, hence inactivating FoxO1, therefore enhancing the hepatic cells' insulin sensitivity. Lut/ZnO NPs have a hepatoprotective effect and may relieve the progression of NAFLD by alleviating insulin resistance, ameliorating the antioxidant status, and regulating the insulin signal pathway.

Improvement of intestinal barrier function, gut microbiota, and metabolic endotoxemia in type 2 diabetes rats by curcumin

ABSTRACT Type 2 diabetes mellitus (T2DM) is known as a complex genetic disease characterized by genetic and environmental factors. The imbalanced intestinal flora and intestinal mucosal barrier are considered to be related to T2DM. Curcumin has been proved to affect the progression of T2DM. T2DM animal was established by low-dose streptozotocin intraperitoneal injection combined with high-fat diet (HFD) feeding. Hematoxylin and eosin (HE) staining and transfer electron microscopy (TEM) were used to observe morphological changes of intestinal tissues of T2DM rats. Insulin and glucose tolerance tests were performed to investigate the influence of curcumin on blood glucose. Curcumin significantly improved the intestinal integrity, hyperglycemia and insulin resistance in diabetic rats. The metabolic endotoxemia induced by HFD in diabetic rats was inhibited remarkably. Curcumin reversed gut microbiota dysbiosis in diabetic rats caused by HFD. We demonstrated that curcumin could protect intestinal mucosal barrier, improve insulin resistance and reduce blood glucose in diabetic rats. This study might provide experimental evidence for the prevention and treatment in T2DM.

Veratrilla baillonii Franch Ameliorates Diabetic Liver Injury by Alleviating Insulin Resistance in Rats.

Type 2 diabetes mellitus (T2DM) is a complex and polygenic disorder with diverse complications. Veratrilla baillonii Franch (V. baillonii) has been applied in the intervention and treatment a diverse range of diseases, including diabetes. In this study, we revealed that water extracts of V. baillonii (WVBF) can ameliorate liver injury and insulin resistance in T2DM rat model. To elucidate the anti-diabetic mechanisms of WVBF, we performed liver transcriptome analysis that displayed WVBF treatment significantly suppressed many gene expressions involved in insulin resistance. Furthermore, functional experiments showed that WVBF treatment reduced the pathological damages of liver and pancreas, which may be regulated by Foxo1, Sirt1, G6pc, c-Met, Irs1, Akt1, Pik3r1. These results indicated that WVBF improves diabetic liver injury and insulin resistance in diabetic rats. Therefore, this study demonstrated WVBF could be used as a promising therapeutic agent for intervention and treatment of diabetes.

Effect of an Aerobic Exercise Course on PI3K and AKT1 Expression and Neural Muscle Insulin Resistance in Diabetic Rats

Objective: The purpose of the present study was to investigate eight weeks of aerobic workout on PI3K and AKT expression as well as insulin resistance (IR) of muscle in diabetic rats by nicotinamide - streptozotocin.&#x0D; Materials and Methods: This laboratory study was conducted on 14 male Wistar rats (8 to 10 weeks) with a weight range of 201 to 250 g and induction of type 2 diabetes (one week). These mice were classified into 2 groups: aerobic training and control group. No exercise was given to the control group during the study, while the aerobic exercise program was run for 5 weeks a week with a gradual increase of speed (10 to 25 m / min) and time (15 to 40 minutes) in running treadmill was performed for the aerobic training group. Assay of gene expression in both study groups was by rt-PCR. For statistical analysis, the SPSS 19 software was used. The variables were compared between the two groups using one-way ANOVA.&#x0D; Results: The findings showed that there was no significant difference between the two groups in terms of IR in diabetic rats (3.85 (± 0.39) vs. 5.26 (± 0.55); P-value= 0.345). The expression of AKT (2.37 (± 2.33) vs. 1.000 (± 0.001); P-value= 0.042) and PI3K (2.87 (± 2.54) vs. 1.000 (± 0.001); P-value= 0.028) in the neural muscle of the training group compared with control group had a significant increase.&#x0D; Conclusion: It seems that performing eight weeks of aerobic exercise could be a strong stimulus for PI3K and AKT gene expression.

An Ayurvedic formulation of Emblica officinalis and Curcuma longa alleviates insulin resistance in diabetic rats: Involvement of curcuminoids and polyphenolics

BackgroundNishamalaki is an Ayurvedic herbal formulation used to treat type 2 diabetes mellitus (T2DM), comprises Emblica officinalis and Curcuma longa. Objective(s)One of the main cause of T2DM is Insulin Resistance (IR) hence, this study was planned to evaluate IR lowering effect of a standardized Nishamalaki extract “EmbliQur” in high-fat diet (HFD) and streptozotocin (STZ) induced T2DM rats. Materials and methodsCurcuminoids (23.89% w/w), gallic acid (5.27% w/w) and tannins (25.44% w/w) were quantified from EmbliQur. Rats were fed HFD throughout the study of 45 days and received STZ (40 mg/kg, i.p) on the 15th day of the study. Rats with more than 250 mg/dl of fasting blood glucose level (FBGL) were considered diabetic and selected for administration of EmbliQur (500 mg and 1000 mg/kg) or the standard drug metformin (120 mg/kg, p.o) from the 18th day of the study for the next 27 days. FBGL and insulin levels of all rats were measured weekly and an oral glucose tolerance test (OGTT) was done at the end of the study. The values of FBGL and insulin were used to calculate IR by the HOMA-IR, QUICKI and Matsuda methods. ResultsRats treated with STZ/HFD had significantly higher than normal FBGL and insulin levels throughout the study and exhibited skewed IR indices in the above three methods of IR assessment. EmbliQur treatment successfully lowered the HFD/STZ-elevated BGL and insulin levels, and ameliorated IR in all models of IR evaluation. ConclusionEmbliQur 1000 mg/kg was noted to be more effective than EmbliQur 500 mg/kg in alleviating IR.

Activation of Hippocampal IR/IRS-1 Signaling Contributes to the Treatment with Zuogui Jiangtang Jieyu Decoction on the Diabetes-Related Depression.

Background Zuogui Jiangtang Jieyu decoction (ZJJ) is mainly used for the treatment of diabetes-related depression in current clinical applications and research. This study aims to investigate whether the brain IR/IRS-1 signaling pathway is involved in the therapeutic effect of ZJJ on depression-like behavior in diabetic rats. Methods Sprague–Dawley rats were fed with high-fat diet and subjected to streptozotocin injection to establish the diabetes animal model. After treatment with different doses of ZJJ (20.530 g/kg or 10.265 g/kg) for 4 weeks, the blood glucose level and peripheral insulin resistance were measured. The forced-swimming test (FST) and Morris water maze test (MWMT) were applied for the mood and cognitive function assessment. Then, the Western blot method was used to analyze the protein levels of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphatidylonositol-3-kinase (PI3K), and protein kinase B (PKB, also as known as AKT) in the hippocampus of diabetic rats. Meanwhile, the immunofluorescence method was performed to analyze the above proteins' expression in the neuron and astrocyte. At last, the levels of glycogen, lactate, and ATP were tested by the ELISA method. Additionally, the insulin-sensitive glucose transporter 4 (GLUT4) and the lactate transporter monocarboxylate transporter 4 (MCT4) were analyzed by the Western blot method. Results ZJJ administration significantly decreased the level of blood glucose and improved the peripheral insulin resistance in diabetic rats. Besides, ZJJ attenuated the depression-like behavior and the cognitive dysfunction in rats with diabetes. Furthermore, we found the upregulation of protein expression of phospho-IR, phospho-IRS-1, phospho-PI3K, and phospho-AKT in the hippocampus of diabetic rats after being treated with ZJJ. Moreover, the above proteins are increased not only in the neuron but also in the astrocyte after ZJJ administration. In addition, ZJJ increased the content of ATP, glycogen, and lactate, as well as the expression of GLUT4 and MCT4 in the hippocampus of diabetic rats. Conclusions These findings suggest that ZJJ improves the depression-like behavior of diabetic rats by activating the IR/IRS-1 signaling pathway in both hippocampal neuron and astrocyte. And the brain IR/IRS-1 signaling pathway plays an important role in astrocyte-neuron metabolic coupling, providing a potential mechanism by which the IR/IRS-1 signaling pathway may contribute to the treatment of ZJJ on diabetes-related depression.

Stimulatory effect of docosahexaenoic acid alone or loaded in zinc oxide or silver nanoparticles on the expression of glucose transport pathway

The role of glucose transporters (GLUTs) in diabetes mellitus has become more prominent as a possible therapeutic target. In the present study, we aimed to compare the effect of zinc oxide nanoparticles (ZnONPs), silver nanoparticles (AgNPs), and docosahexaenoic acid (DHA) alone or loaded in ZnONPs or AgNPs on insulin signaling pathway and GLUTs expression in diabetic rats. In the experimental part, rats were divided into seven groups; control, diabetic, and the other five groups were diabetic received different treatments. Fasting blood sugar (FBS), serum level of insulin, insulin resistance (IR), and serum level of phosphatidylinositol 3-kinase (PI3K) were evaluated. In addition, insulin expression in pancreatic islets was assessed by immunohistochemical analysis, and the expression of liver GLUTs 1, 2, and 4 and liver insulin receptor substrate-1 (IRS-1) was evaluated by real-time polymerase chain reactions (RT-PCR).The results of the current study showed that ZnONPs, AgNPs, and DHA alone or loaded in ZnONPs or AgNPs attenuated levels of FBS, insulin and decreased IR in diabetic rats through enhancing the expression of GLUTs as well as IRS-1 and PI3K. Furthermore, AgNPs loaded with DHA showed the most significance with high comparability to the control group.In conclusion, this study elucidated the role of GLUTs and IRS-1 in diabetes and introduced novel characteristics of ZnONPs, AgNPs, and DHA alone or loaded in ZnONPs or AgNPs as a therapeutic modality to activate GLUTs and IRS1, which may be beneficial for diabetic patients with IR.

β-Sitosterol Circumvents Obesity Induced Inflammation and Insulin Resistance by down-Regulating IKKβ/NF-κB and JNK Signaling Pathway in Adipocytes of Type 2 Diabetic Rats.

β-sitosterol (SIT), the most abundant bioactive component of vegetable oil and other plants, is a highly potent antidiabetic drug. Our previous studies show that SIT controls hyperglycemia and insulin resistance by activating insulin receptor and glucose transporter 4 (GLUT-4) in the adipocytes of obesity induced type 2 diabetic rats. The current research was undertaken to investigate if SIT could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of SIT (20 mg/kg b.wt) was administered orally for 30 days to high fat diet and sucrose induced type-2 diabetic rats. Metformin, the conventionally used antidiabetic drug was used as a positive control. Interestingly, SIT treatment restores the elevated serum levels of proinflammatory cytokines including leptin, resistin, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to normalcy and increases anti-inflammatory adipocytokines including adiponectin in type 2 diabetic rats. Furthermore, SIT decreases sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator–activated receptor-γ (PPAR-γ) gene expression in adipocytes of diabetic rats. The gene and protein expression of c-Jun-N-terminal kinase-1 (JNK1), inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) and nuclear factor kappa B (NF-κB) were also significantly attenuated in SIT treated groups. More importantly, SIT acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that SIT inhibits obesity induced insulin resistance by ameliorating the inflammatory events in the adipose tissue through the downregulation of IKKβ/NF-κB and c-Jun-N-terminal kinase (JNK) signaling pathway.

Berberine Ameliorates Glucose Metabolism in Diabetic Rats through the alpha7 Nicotinic Acetylcholine Receptor-Related Cholinergic Anti-Inflammatory Pathway.

Berberine is an isoquinoline derivative alkaloid extracted from Chinese herbs. Recent studies have demonstrated the therapeutic effect of berberine on glucose metabolic disorders. However, its specific mechanism is still unclear. Our study aimed to research the glucose-lowering effect of berberine in diabetic rats and to reveal the possible role of the cholinergic anti-inflammatory pathway. Diabetic rats induced by administration of a high-calorie diet and streptozocin tail vein injection were assessed by the oral glucose tolerance test. Then, the diabetic rats were divided into two groups, those with or without the alpha7 nicotinic acetylcholine receptor gene downregulated, respectively, followed by treatment including berberine for 6 weeks. Results of this study show that the administration of berberine downregulated levels of fasting blood glucose and fasting insulin, and ameliorated insulin resistance in diabetic rats. Treatment with berberine inhibited acetylcholinesterase activity, and upregulated acetylcholine levels in the serum and alpha7 nicotinic acetylcholine receptor gene expression in the liver tissue. Meanwhile, berberine reversed elevated expression of cytokines interleukin-1β and TNF-α in the serum and downregulated nuclear factor κB expression. However, berberine administration showed no glucose-lowering or anti-inflammatory effect in diabetic rats in which alpha7 nicotinic acetylcholine receptor gene expression was downregulated, and acetylcholinesterase activity was also significantly inhibited. In conclusion, berberine may ameliorate glucose metabolism by activating the alpha7 nicotinic acetylcholine receptor-mediated cholinergic anti-inflammatory pathway.