Skeletal Muscle Of Diabetic Rats Research Articles

High-intensity interval training increases AMPK and GLUT4 expressions via FGF21 in skeletal muscles of diabetic rats

Background: In type 2 diabetes, a decrease in expression of glucose transporter type 4 (GLUT4) can result in decreased glucose uptake. The hormone fibroblast growth factor 21 (FGF21) promotes glucose uptake. The liver and other organs, such as the muscles, produce FGF21. Physical activity increases FGF21 secretion from skeletal muscles. FGF21 is thought to promote glucose uptake during exercise by activating AMP-activated protein kinase (AMPK). As a result, the goal of this study is to determine how HIIT affects glucose uptake via FGF21 signaling in diabetics. Methods: Twenty-four eight-week-old male Wistar rats were randomly divided into four categories: (1) without intervention (Con), (2) DM intervention (ConDM), (3) DM group undergoing continuous training (DM-CT), and (4) DM group undergoing high-intensity interval training (DM-HIIT). The trainings in the exercise groups (DM-CT and DM-HIIT) were performed six days a week for six weeks. We analyzed FGF21 levels in serum and muscles by ELISA. Measurement of phosphorylated AMPK in muscles used ELISA, and that of mRNA GLUT4 expression used RT-PCR. Results: Following HIIT interventions, the glucose level in plasma was closer to normal level. An increase in FGF21 levels aided in the reduction in blood glucose. The HIIT group had significantly higher FGF21 levels in serum and muscles. An increase in FGF21 was followed by an increase in AMPK phosphorylation and GLUT4 expression in the HIIT group. Conclusions: In diabetic rats, HIIT promotes glucose uptake via FGF21, which activates AMPK and increases GLUT4 expression.

Effect and mechanism of TSH on GLUT4 in skeletal muscle of diabetic rats

Effect and mechanism of TSH on GLUT4 in skeletal muscle of diabetic rats

Ameliorative effects of phlorotannin-rich fraction of Sargassum tenerrimum in high-fat diet and low dose streptozotocin-induced metabolic changes and oxidative stress in diabetic rats

Introduction: Type 2 diabetes mellitus (T2D) is a progressing polygenic disease demanding a multitargeted treatment strategy. Sargassum tenerrimum (ST) is a marine brown alga with potentially bioactive chemicals that could be used as innovative biotherapeutics for diabetes treatment. The current research examined the potential of the phlorotannin-rich fraction from S. tenerrimum (PST) to mitigate diabetes in Wistar albino rats induced with high-fat diet (HFD) and streptozotocin (STZ) administration. Methods: Diabetic rats were given PST (200 and 400 mg/kg) or metformin (250 mg/kg) orally three weeks, and followed by the measurements of insulin, glycemic factors, biological markers of oxidative stress, tumor necrosis factor-alpha (TNF-α), as well as hepatic and pancreatic histopathological changes. Results: PST treatment significantly decreased fasting blood glucose, insulin resistance, lipid profile, hepatic profile, and TNF- α levels and improved serum insulin and glucose tolerance in diabetic rats. In the skeletal muscles of diabetic rats, PST led to a significant rise in antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) reductase, and a decrease in lipid peroxidation. Furthermore, PST treatment significantly reduced pancreatic-cell damage and hepatic fatty accumulation. PST was more efficacious at 400 mg/kg exhibiting a dose-dependent effect. Conclusion: PST improves glucolipid metabolism in HFD and STZ-induced diabetic rats, probably by reducing hyperglycemia, insulin resistance, dyslipidemia, oxidative stress, inflammation, and damage to pancreatic and hepatic architectures. The findings suggest that PST has a curative impact on diabetes mellitus type 2 and represents a new subject of study for the treatment of diabetes naturally.

Irisin/FNDC5 influences myogenic markers on skeletal muscle following high and moderate-intensity exercise training in STZ-diabetic rats.

In the present study, we investigated the effects of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) on irisin and expression of myogenic markers (paired box 7 (Pax7), myogenic differentiation 1 (MyoD), myogenin) in skeletal muscle of diabetic rats. Eighty-four male Wistar rats (6weeks of age) were randomly divided into seven groups (n = 12): basic control (Co Basic), 8weeks control (Co 8w), diabetes mellitus (DM), HIIT, DM + HIIT, MICT, and DM + MICT groups. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ). The protocol was characterized by running on a rodent treadmill with moderate intensity (60-70% ), 60min per session, 5days/week, for 6weeks. HIIT consisted of six 3-min runs at a high intensity (80-90% ) alternated with 2-min running at low intensity (50% ), 30min per session, 5days/week, for 6weeks. Results showed that DM decreased myoblast markers compared to Co Basic and Co 8w groups. Fibronectin type III domain-containing protein 5 (FNDC5) mRNA decrease was correlated with myoblast markers (Pax7 r = 0.632, p = 0.027; MyoD r = 0.999, p = 0.001; myogenin r = 1.000, p = 0.001) in DM group. DM + MICT significantly increased gene expression of MyoD, myogenin, and FNDC5 compared to DM and DM + HIIT. The results also showed that the intensity and duration of exercise on the treadmill were effective in stimulating irisin and myogenic markers after DM.

The effect of resistance and endurance training with ursolic acid on atrophy-related biomarkers in muscle tissue of diabetic male rats induced by streptozotocin and a high-fat diet.

In this study, the effect of resistance and endurance training with/without ursolic acid supplementation was evaluated to identify atrophy-related biomarkers in elderly rats induced by diabetes and a high-fat diet (HFD) based on in silico analysis algorithms and pharmaceutical methods. The visualizer software found differential gene expression levels in skeletal muscle atrophy via computed hub gene network parameters. Also, the impact of ursolic acid, as a potent inducer of the Trp53 protein in ameliorating decreased muscle mass, was analyzed in diabetic rats. Fifty-six-old male Wistar rats were randomly assigned into seven groups, including healthy control (Control), diabetic control (DM), Ursolic acid supplementation (UA), resistance training (RT), endurance training (ET), resistance training+ Ursolic acid supplementation (RT + U), and endurance training in combination with Ursolic acid supplementation (ET + U). Exercise intervention included 8 weeks of resistance or endurance training programs. Biomedical informatic outputs determined the P53 signaling pathway as a remarkable causative factor in the pathomechanism of atrophy. In addition, the results demonstrated that exercise and supplementation of UA impeded the interactions among p53/ATF4/p21. Moreover, ET and ursolic acid had a synergetic effect on the signaling pathway of p53/ATF4/p21 and probably could inhibit the aging process and modulate the p53/ATF4/p21 molecular pathway. The interaction between UA and endurance exercise significantly modified the activity of the p53/ATF4/p21 signaling pathway. Based on in silico studies, the p53/ATF4/p21 pathway plays an essential role in aging, and the inhibition of this pathway would be beneficial in decelerating the aging process. PRACTICAL APPLICATIONS: Ursolic acid (UA) is a natural pentacyclic triterpenoid carboxylic acid found in apples (a major compound of apple wax) and other fruits; it is known to improve skeletal muscle function and reduce the muscular atrophy pathways. We indicated that p53/ATF4/p21 signaling is an essential factor in aging, and the suppression of this pathway could be beneficial in the deceleration of the aging process. Therefore, this work would shed light on understanding the effect of exercise and nutrition interventions on preventing atrophy markers of skeletal muscle in diabetic rats. Further studies are needed to seek the precise mechanism of the synergism between UA and exercise in ameliorating atrophy markers.

Antidiabetic with antilipidemic and antioxidant effects of flindersine by enhanced glucose uptake through GLUT4 translocation and PPARγ agonism in type 2 diabetic rats

Ethnopharmacological relevanceMedicinal plants have been used by the people of developing countries to treat various diseases. WHO also recommends the use of medicines from plants source. In that, diabetes also one of the diseases that have been treated traditionally by several people all over the world. In India, Toddalia asiatica (L.) Lam. (Rutaceae) is also a medicinal plant used traditionally for the treatment of diabetes in Ayurveda. Moreover, T. asiatica is also used in a polyherbal formulation to treat diabetes. Aim of the studyThis study examined the antidiabetic with antilipidemic and antioxidant effects of flindersine isolated from T. asiatica leaves. Materials and methodsDiabetes was induced in Wistar rats by feeding a high-fat diet (HFD) for 15 days and injecting a single dose of 40 mg/kg b. wt. of Streptozotocin (STZ). Five days post-injection, the grouped diabetic rats were treated with 20 and 40 mg/kg of flindersine. ResultsFlindersine resulted in a clear decline of blood glucose levels during 28 days of treatment in two different doses. Flindersine also significantly (P ≤ 0.05; P ≤ 0.005) reduced the body weight gain, plasma insulin concentration, urea, creatinine, total cholesterol (TC), triglycerides (TG) and free fatty acids (FFA) levels and significantly increased (P ≤ 0.05; P ≤ 0.005) the total protein level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities compared to the standard drug, pioglitazone. Additionally, flindersine restored the glucose transporter protein 4 (GLUT4), adenosine monophosphate protein kinase (AMPK) and peroxisome proliferator-activated receptor γ (PPARγ) expressions in adipose tissues and skeletal muscles. ConclusionIt has been found that flindersine has potent antilipidemic and antidiabetic activities by improving insulin sensitivity by enhancing the phosphorylation of AMPK, GLUT4 translocation, and PPARγ agonism on adipose tissue and skeletal muscles of diabetic rats.

Bitter gourd extract improves glucose homeostasis and lipid profile via enhancing insulin signaling in the liver and skeletal muscles of diabetic rats

Objective: To investigate the modulatory effects of bitter gourd extract on the insulin signaling pathway in the liver and skeletal muscle tissues of diabetic rats. Methods: The ethanolic extract of bitter gourd was prepared and its contents of total polyphenols and flavonoids were assayed. A neonatal streptozotocin-induced diabetic rat model was established and the diabetic rats were assigned into different groups and were treated with different doses of bitter gourd extract (100, 200, 400, or 600 mg/kg) or with glibenclamide (0.1 mg/kg) for 30 d. Fasting blood glucose, insulin, and lipid profile were evaluated and the insulin signaling pathway in the liver and skeletal muscle of rats was investigated. The correlations between homeostasis model assessment (HOMA) and the components of insulin signaling pathway were also evaluated. Results: Different doses of bitter gourd extract significantly ameliorated fasting blood glucose level and HOMA index for insulin resistance. Moreover, bitter gourd extract increased serum insulin and improved disrupted serum lipid profile. The levels of insulin receptor substrate-1 (IRS-1), p-insulin receptor β (p-IR-β), protein kinase C (PKC), GLUT2, and GLUT4 were improved by treatment with bitter gourd extract. The best results were obtained with 400 mg/kg dose of the extract, the effect of which was equivalent to that of glibenclamide. HOMA in the bitter gourd treated rats was negatively correlated with p-IR-β, IRS-1 and PKC in hepatic and skeletal muscle. HOMA was also negatively correlated with skeletal muscle GLUT4. Conclusions: Bitter gourd extract improves glucose homeostasis and lipid profile in diabetic rats via enhancement of insulin secretion and sensitivity. Therefore, bitter gourd can be used as a potential pharmacological agent for the treatment of type 2 diabetes mellitus.

The effects of exercise training on Kinesin and GAP-43 expression in skeletal muscle fibers of STZ-induced diabetic rats

Kinesin-1 and Growth Associated Protein 43 (GAP-43) localization in muscle fiber are crucial for proper skeletal muscle hypertrophy. To evaluate this assumption, we investigated the beneficial effects of endurance training on GAP-43 and Kinesin Family Member 5B (KIF5B) expression in gastrocnemius muscle of streptozotocin (STZ)-induced diabetic rats. Fifty-two male rats were randomly divided into four groups: healthy control (C), healthy trained (T), diabetic control (DC) and diabetic trained (DT). Diabetes was induced by a single intraperitoneal injection of STZ (45 mg/kg). The rats in DT and T groups were subjected to treadmill running for 5 days a week over 6 weeks. The results indicated that the GAP-43 and KIF5B protein levels in the DC group were significantly lower than those in the C group. Additionally, chronic treadmill running in diabetic rats was accompanied by significant increase of GAP-43 and KIF5B protein expression, compared to DC group. Furthermore, the endurance training in healthy rats was associated with a significant increase of GAP-43 and KIF5B protein levels. In addition, we found positive correlation between GAP-43 and KIF5B protein levels and myonuclear number per fiber and average gastrocnemius cross-sectional area (CSA). GAP43 and KIF5B protein levels were decreased in skeletal muscles of diabetic rats, and exercise training had beneficial effects and could restore their abnormal expression. Moreover, there is a strong relationship between muscle hypertrophy and GAP-43 and KIF5B protein levels.

Inhibition of NOX2 Improves Muscle Tension and Fatigue Resistance in Fast Twitch Skeletal Muscle of Diabetic Rats

Chronic hyperglycemic state during diabetes mellitus (DM) has been related to an increase in oxidative stress, which causes damage to skeletal muscle tissue, contributing to the appearance of muscle fatigue, characterized by decreased strength. An increase in the activity of the enzyme NADPH oxidase 2 (NOX2) has been observed in skeletal muscle, and with it an increase in basal ROS production; It has been linked to the alteration of insulin signaling in tissue. Consequently, normal muscle metabolism is affected, compromising the ability of individuals to perform physical activity. Apocynin is a drug that, in addition to being a specific inhibitor of NADPH oxidase, has antioxidant properties reported in experimental models of insulin resistance. However, the effect of NOX2 inhibition on skeletal muscle health during DM is unknown. Therefore, in order to preserve muscle structure and function, the objective of this study was to evaluate the effect of NOX2 inhibition by apocynin on muscle function in an experimental diabetes model. Male Wistar rats (230–250 g) were randomly divided into four groups, among them: control, apocynin control, diabetic and apocynin diabetic, in which diabetes was induced intraperitoneally with streptozotocin (45 mg / kg). Treatment with apocynin (3 mg / kg / day) was administered for 8 weeks and at the end of the treatment, the extensor digitorum longus (EDL) muscles were isolated and an isometric tension protocol was performed (repetitive electrical stimulation: pulses of 100 V, 300 ms duration and frequency 45 and 50 Hz, respectively). Treatment with apocynin contributed to a significant increase in the time of resistance to fatigue (88.23%; p <0.05) and improved the maximum muscle tension (72.23%; p <0.5) and total (80%; p <0.5) compared to the diabetic group. Additionally, a positive effect on weight and a decrease in blood glucose level was observed. Together, these results indicate that NOX2 inhibition exerted a protective effect on skeletal muscle tissue during diabetes.

Phosphodiesterase 4 inhibition restrains muscle proteolysis in diabetic rats by activating PKA and EPAC/Akt effectors and inhibiting FoxO factors

AimThere is growing evidence about the ability of cyclic adenosine monophosphate (cAMP) signaling and nonselective phosphodiesterase (PDE) inhibitors on mitigate muscle atrophy. PDE4 accounts for the major cAMP hydrolyzing activity in skeletal muscles, therefore advances are necessary about the consequences of treatment with PDE4 inhibitors on protein breakdown in atrophied muscles. We postulated that rolipram (selective PDE4 inhibitor) may activate cAMP downstream effectors, inhibiting proteolytic systems in skeletal muscles of diabetic rats. Main methodsStreptozotocin-induced diabetic rats were treated with 2 mg/kg rolipram for 3 days. Changes in the levels of components belonging to the proteolytic machineries in soleus and extensor digitorum longus (EDL) muscles were investigated, as well as cAMP effectors. Key findingsTreatment of diabetic rats with rolipram decreased the levels of atrogin-1 and MuRF-1 in soleus and EDL, and reduced the activities of calpains and caspase-3; these findings partially explains the low ubiquitin conjugates levels and the decreased proteasome activity. The inhibition of muscle proteolysis may be occurring due to phosphorylation and inhibition of forkhead box O (FoxO) factors, probably as a consequence of the increased cAMP levels, followed by the activation of PKA and Akt effectors. Akt activation may be associated with the increased levels of exchange protein directly activated by cAMP (EPAC). As a result, rolipram treatment spared muscle mass in diabetic rats. SignificanceThe antiproteolytic responses associated with PDE4 inhibition may be helpful to motivate future investigations about the repositioning of PDE4 inhibitors for the treatment of muscle wasting conditions.

Effects of Quercetin and Coenzyme Q10 on Biochemical, Molecular, and Morphological Parameters of Skeletal Muscle in Trained Diabetic Rats.

Diabetes mellitus (DM) affects the musculoskeletal system through its metabolic perturbations. Exercise modulates blood sugar levels and increases the body's sensitivity to insulin in patients with DM. This study aimed to investigate the potential effects of combined quercetin and coenzyme Q10 (CoQ10) supplements with or without exercise on the histological, biochemical and molecular structures of diabetic rat's skeletal muscle Methods: A total of 64 adult male albino rats were divided into six groups: control, trained nondiabetic, non-trained diabetic, diabetic rats treated with combined CoQ10 and quercetin, diabetic rats with treadmill training, and diabetic rats treated with treadmill training and CoQ10 and quercetin. Blood and skeletal muscle samples were obtained from all groups for routine histological examination and biochemical determination of cytokine levels and protein activities. Quantitative real-time polymerase chain reaction (qRT-PCR) and morphometric analysis of PAS and Bax expressions were also performed. Biochemical analysis revealed improvement in all studied parameters with combined Co- Q10 and quercetin than exercise training alone. Combined treatment and exercise showed significant improvement in all parameters especially interleukin 6 and malondialdehyde. Fibronectin type III domain-containing protein 5 (FNDC5) expression and irisin levels increased in all trained groups but combined treatment with exercise significantly increased their levels than exercise alone. Histological analysis revealed improvement after exercise or combined treatment; however, when exercise was combined with CoQ10 and quercetin, marked improvement was observed. the combination of CoQ10 and quercetin could be promising in preserving musculoskeletal function in patients with DM concomitantly with physical exercise.

Resveratrol reduces excessive cholesterol accumulation in Goto-Kakizaki rat, a model with congenital type 2 diabetes.

Resveratrol (3, 5, 3'-trihydroxystilbene) is a naturally-occurring, biologically active compound having numerous beneficial effects in the organism, including anti-diabetic properties. Its anti-diabetic action have been relatively well established using various animal models, however, in Goto-Kakizaki (GK) rats is poorly explored. These animals are non-obese and have a congenital type 2 diabetes. In the present study, effects of resveratrol on cholesterol content, blood levels of some hormones (thyroxine, triiodothyronine, ghrelin and spexin), glucose and parameters indirectly related with renal function (creatinine, urea nitrogen, total protein and albumin) were explored in GK rats. GK and control rats were treated with resveratrol for 10 weeks at the dose of 20 mg/kg body weight. It was shown that cholesterol content was significantly increased in the blood, liver and the skeletal muscle of diabetic rats, compared with the control animals. However, the resveratrol therapy was associated with a markedly reduced tissue cholesterol content. Our study also demonstrated that blood levels of thyroxine (T4) were decreased, and triiodothyronine (T3) increased in GK rats. These alterations were, however, not significantly affected by resveratrol. GK rats had elevated blood glucose levels, but hyperglycemia was not ameliorated by resveratrol. It was also shown that blood creatinine levels were increased in diabetic rats. However, in animals subjected to the resveratrol therapy, the blood creatinine level was unchanged. Concentrations of ghrelin, spexin and other blood parameters indirectly related with the renal function were shown to be similar in GK and control rats. These results indicate that resveratrol beneficially influences cholesterol concentrations in tissues of diabetic rats; however, it is ineffective in the case of thyroid hormones and glucose. Moreover, it was shown that resveratrol did not induce any significant effects in non-diabetic animals.

Olive Leaf Polyphenols (OLPs) Stimulate GLUT4 Expression and Translocation in the Skeletal Muscle of Diabetic Rats.

Skeletal muscles are high-insulin tissues responsible for disposing of glucose via the highly regulated process of facilitated glucose transporter 4 (GLUT4). Impaired insulin action in diabetes, as well as disorders of GLUT4 vesicle trafficking in the muscle, are involved in defects in insulin-stimulated GLUT4 translocation. Since the Rab GTPases are the main regulators of vesicular membrane transport in exo- and endo-cytosis, in the present work, we studied the effect of olive leaf polyphenols (OLPs) on Rab8A, Rab13, and Rab14 proteins of the rat soleus muscle in a model of streptozotocin (SZT)-induced diabetes (DM) in a dose-dependent manner. Glucose, cholesterol, and triglyceride levels were determined in the blood, morphological changes of the muscle tissue were captured by hematoxylin and eosin histological staining, and expression of GLUT4, Rab8A, Rab13, and Rab14 proteins were analyzed in the rat soleus muscle by the immunofluorescence staining and immunoblotting. OLPs significantly reduced blood glucose level in all treated groups. Furthermore, significantly reduced blood triglycerides were found in the groups with the lowest and highest OLPs treatment. The dynamics of activation of Rab8A, Rab13, and Rab14 was OLPs dose-dependent and more effective at higher OLP doses. Thus, these results indicate a beneficial role of phenolic compounds from the olive leaf in the regulation of glucose homeostasis in the skeletal muscle.

Nicorandil Attenuates High Glucose-Induced Insulin Resistance by Suppressing Oxidative Stress-Mediated Endoplasmic Reticulum Stress Protein Kinase RNA-Like Endoplasmic Reticulum Kinase Singling Pathway

Background: Glucose- induced insulin resistance (IR) is a typical character of diabetes. Nicorandil is widely used in ischemic heart disease. Nicorandil shows protective effects against oxidative and endoplasmic reticulum (ER) stress which are involved in insulin resistance. Here we investigated mechanisms of nicorandil’s novel pharmacological activity on IR in diabetes. Methods: Nicorandil was administrated to diabetic animals and high-glucose exposed skeletal muscle cells. IR and glucose tolerance were evaluated. Molecular mechanisms concerning oxidative stress, ER stress and glucose uptake were assessed. Findings: Nicorandil attenuated high- glucose induced IR without affecting fasting blood glucose and glucose tolerance in whole body and skeletal muscle in diabetic rats. Nicorandil treatment suppressed protein kinase C(PKC)/ nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) system activities by reducing cytoplasmic free calcium level in skeletal muscle cells exposed to high glucose. As a result, the oxidative stress- mediated ER stress protein kinase RNA- like endoplasmic reticulum kinase (PERK)/ eukaryotic initiation factor (EIF) 2α/ activating transcription factor (ATF)4/CEBP homologous protein (CHOP)/tribbles homolog (TRB)3 signaling pathway activation was inhibited. Nicorandil down-regulated expression of TRB3 and thus facilitated Akt phosphorylation in response to insulin stimulation, leading to glucose transporter (GLUT)4 plasma membrane translocation which promoted glucose uptake capability of skeletal muscle cells. Interpretation: By reducing cytoplasmic calcium, nicorandil alleviated high-glucose induced IR by inhibiting oxidative stress- mediated ER stress PERK pathway. This study indicated nicorandil as a promising agent in treatment of patients with ischemic heart disease complicated with diabetes. Funding Statement: This study was supported by Innovative Talents Promotion Project of Shaanxi Province (2019KJXX-019); Fundamental Scientific Research Foundation of Xi’an Jiaotong University (xzy012019131); Health Scientific Foundation of Shaanxi Province (2018E11); Natural Science Basic Research Foundation of Shaanxi Province (2020JQ-941). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The experimental protocols were reviewed and approved by Institutional Animal Care and Use Committee of Medical Research Institute of Northwestern Polytechnical University.

Protective effects of low-intensity exercise on metabolic oxidative capacity and capillarization in skeletal muscle of non-obese diabetic rats.

Diabetes mellitus induces skeletal muscle dysfunction, such as decreased metabolic activity and capillarization. This study aimed to investigate the effects of aerobic low intensity exercise training on metabolic oxidative capacity and capillarization in skeletal muscle of non-obese diabetic rats. Eleven to twenty-five week-old male non-obese Spontaneous Diabetic Torii (SDT) rats (n = 11) and age-matched healthy male Sprague-Dawley SD rats (n = 11) were randomly assigned to either exercise or sedentary groups. The exercise training was performed on a low-speed motorized treadmill (15 m min-1) for 60 min per session, 5 sessions per week for 14 weeks in exercised groups. Sedentary SDT rats resulted in hyperglycemia, reduction of metabolic oxidative enzyme, and low percentage of oxidative fibers in the skeletal muscles. The low-intensity exercise training inhibited the growth-related increase in glucose level, and increased the muscle oxidative enzyme in exercised SDT rats compared with sedentary SDT rats. In addition, the exercise program prevented capillary regression in the skeletal muscle of diabetic rats. These results suggest that low-intensity exercise training may be an effective treatment to counter the detrimental effects of type 2 diabetes mellitus on the oxidative capacity and the capillary network of skeletal muscles.

Physicochemical Characterization of Hizikia fusiforme Polysaccharide and Its Hypoglycemic Activity via Mediating Insulin-Stimulated Blood Glucose Utilization of Skeletal Muscle in Type 2 Diabetic Rats.

In the current study, a functional polysaccharide fraction (HFP) was obtained from Hizikia fusiforme by ultrasound-assisted enzymatic extraction, and its structural characterization and hypoglycemic activity and potential molecular mechanism were investigated. The results indicated that HFP with high uronic acid was a heterogeneous polysaccharide composed of six monosaccharides. Congo red test explained that HFP had no triple helix conformation. AFM analysis revealed that HFP was spherical particle with flame-like aggregates and multiple strands closely arranged. Rheological analysis showed that HFP exhibited shear-thinning flow behavior. HFP significantly ameliorated diabetes-related symptoms and serum profiles and increased muscle glycogen storage in rats. HFP administration at 400 mg/kg body weight/day displayed greater advantages than metformin in controlling the levels of fasting blood glucose, triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bile acid (TBA) of diabetic rats. Intervention of HFP up-regulated markedly the expression of AMPK-α, GLUT4, PI3K and Akt in skeletal muscle of diabetic rats at the mRNA and protein levels, revealing hypoglycemic effects of HFP may be related closely to improving insulin resistance and mitochondrial function of skeletal muscle.

Mitigation mechanisms of Hizikia fusifarme polysaccharide consumption on type 2 diabetes in rats

The objective of current work was to explore the potential anti-diabetic mechanisms of Hizikia fusifarme polysaccharide (HFP) in type 2 diabetic rats. The carbohydrate loading experiment illustrated that HFP supplement could reduce blood sugar fluctuations caused by eating through inhibiting the hydrolysis of starch in mice. The analysis of typically diabetic symptoms and serum profiles showed that oral administration of HFP could mitigate hyperglycemia, insulin resistance, dyslipidemia, chronic inflammation and oxidative stress in rats. The 16s rRNA gene sequencing analysis indicated that HFP treatment could restore beneficial composition of gut flora in diabetic rats, and the correlation analysis revealed that the improvement of diabetes is closely related to the modification of gut flora by HFP intervention. Furthermore, the RT-qPCR and western blotting analysis clarified that HFP administration could increase glycogen storage in liver and skeletal muscle of diabetic rats through activating IRS/PI3K/AKT/GLUT signaling pathway and restrain gluconeogenesis via affecting the relative expression of Egr-1 and PEPCK genes.

Resveratrol ameliorates inflammatory and oxidative stress in type 2 diabetic Goto-Kakizaki rats

Type 2 diabetes is associated with inflammatory and oxidative stress. Resveratrol, a naturally occurring diphenolic compound, was shown to improve glycemic control and alleviate metabolic disturbances in Goto-Kakizaki (GK) rats, a non-obese model of type 2 diabetes. However, in GK rats effects of resveratrol addressing inflammatory and oxidative stress were not explored. The present study aimed to determine anti-inflammatory and anti-oxidative properties of resveratrol in these rats. GK and Sprague-Dawley (SD) rats were divided into 4 groups: GK control, GK treated with resveratrol, SD control and SD treated with resveratrol. Resveratrol (20 mg/kg b.w.) was given once a day for 10 weeks. It was shown that contents of inflammatory markers, interleukin 6 (IL-6), interleukin 1 β (IL-1β), tumor necrosis factor α (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), were increased in the skeletal muscle of diabetic rats, but these effects were prevented by resveratrol therapy. Similarly, amounts of IL-1β and TNF-α were elevated in livers of GK rats; however, this rise was alleviated in resveratrol-treated animals. Moreover, the contents of inflammation-related factors (IL-6, IL-1β, TNF-α and NF-κB) were augmented in adipose tissue of GK rats; nevertheless, in this tissue resveratrol was ineffective. Resveratrol reduced also lipid peroxidation in the skeletal muscle, reduced activities of glutathione peroxidase in blood serum and catalase in the livers of GK rats. Our new findings show that resveratrol therapy results in relieving inflammatory and oxidative stress in GK rats, which may be largely associated with the alleviation of metabolic disturbances in this model of diabetes. Nevertheless, it was demonstrated that the efficacy of resveratrol action is tissue-specific.

Effect of resveratrol on SNARE proteins expression and insulin resistance in skeletal muscle of diabetic rats.

Objective(s):Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex proteins are involved in membrane trafficking. The expression of isoforms of SNAP-23, syntaxin-4, and VAMP-2 is significantly done in skeletal muscles; they control GLUT4 trafficking. It is believed that type 2 diabetes could be caused by the modifications in the expression of SNARE complex proteins. The purpose of this study was to evaluate the effect of resveratrol on the expression of these proteins in type 2 diabetes.Materials and Methods:Forty male Wistar rats were selected. Streptozotocin and nicotinamide were applied for the induction of type 2 diabetes. The animals were divided into five groups. Healthy and diabetic groups were set as control; resveratrol (1, 5, and 10 mg/kg body weight) was applied to treat the three groups of diabetic rats for 30 days. Real-time qRT-PCR was applied to evaluate the expression of SNARE complex proteins.Results:There is a link between diabetes and insulin resistance and up-regulation of SNARE proteins expression. Resveratrol improved hyperglycemia and insulin resistance along with a non-significant reduction in the expression of SNARE proteins.Conclusion:Increased expression of SNARE proteins was possibly a compensatory mechanism in response to insulin resistance in the skeletal muscles of diabetic rats. Resveratrol non-significantly reduced the expression of SNARE proteins by enhancing insulin sensitivity, where this effect was dose-dependent. Thus, higher doses of resveratrol and longer intervention periods could probably be more effective. Another molecular mechanism of the anti-diabetic properties of resveratrol was identified with an effect on the expression of SNARE proteins.

The effect of cassia seed extract on the regulation of the LKB1\u2013AMPK\u2013GLUT4 signaling pathway in the skeletal muscle of diabetic rats to improve the insulin sensitivity of the skeletal muscle

BackgroundThis study aimed to observe the hypoglycemic effect of cassia seed extract in rats with type-2 diabetes mellitus and its effect on reducing insulin resistance in the skeletal muscle.Methods50 rats were randomly divided into the normal, model, high-dose, middle-dose, and low-dose groups of cassia seed extract (n = 10 each). A high-fat diet combined with streptozotocin administration was adopted to build type 2 diabetes models. The cassia seed extract groups were fed different concentrations cassia seed extract while the normal and model groups were fed the same volume of normal saline. The weight, FINS, GIR, insulin tolerance, blood glucose and blood lipid level, oxidative stress indices and expressions related to the LKB1–AMPK–GLUT4 pathway were detected and compared between the two groups.ResultsCompared with the normal group, the model group showed lower weight, glucose infusion rate and expressions related to LKB1–AMPK–GLUT4 pathway and higher FINS, insulin tolerance, blood glucose and blood lipid level and oxidative stress indices (all P < 0.05). Compared with the model group, higher weight, glucose infusion rate and expressions related to LKB1–AMPK–GLUT4 pathway and lower FINS, insulin tolerance, blood glucose and blood lipid level and oxidative stress indices were observed in all groups that were administered cassia see extract (all P < 0.05).ConclusionCassia seed extract could noticeably improve the insulin resistance of diabetic rats and enhance the insulin sensitivity of their skeletal muscles. Its mechanism may be related to damage repair of the LKB1–AMPK–GLUT4 signaling pathway and oxidative stress in the skeletal muscle.