Skeletal Muscle Of Diabetic Rats Research Articles

Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway.

Oxidative stress plays a key role in the pathogenesis of diabetic myopathy. Celastrol provides a wide range of health benefits, including antioxidant, anti-inflammatory and antitumor effects. We hypothesized that celastrol may exert an antioxidant effect in the skeletal muscle of diabetic rats. In the present study, MnSOD activity was determined by spectrophotometry. The protein levels were evaluated by western blot analysis and mRNA content was quantified by RT-qPCR. We firstly found that the levels of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor coactivator 1α (PGC1α), silent mating-type information regulation 2 homolog 3 (SIRT3) and manganese superoxide dismutase (MnSOD) were all decreased in the skeletal muscle of diabetic patients. Male rats with diabetes were also treated with the vehicle or with celastrol at 1, 3 and 6 mg/kg/day for 8 weeks. The administration of celastrol at 3 and 6 mg/kg attenuated the deterioration of skeletal muscle, as shown by histological analysis, decreased the malondialdehyde (MDA) level and increased the glutathione (GSH) level assayed by enzyme-linked immunosorbent assay (ELISA) method. It also enhanced the enzyme activity and increased the expression of MnSOD, and increased the AMPK phosphorylation level, as well as PGC1α and Sirt3 expression. The findings of our study suggest that the expression of AMPK, PGC1α, SIRT3 and MnSOD are decreased in the skeletal muscle of diabetic patients. Celastrol exerted antioxidant effects on skeletal muscle partly by regulating the AMPK-PGC1α-SIRT3 signaling pathway.

Central injection of GALR1 agonist M617 attenuates diabetic rat skeletal muscle insulin resistance through the Akt/AS160/GLUT4 pathway

Insulin resistance of skeletal muscle plays an important role in the pathogenesis of type 2 diabetes. Galanin, a 29/30-amino-acid neuropeptide, plays multiple biological actions, including anti-diabetic effects. Although recent results of our study showed that administration of galanin could mitigate insulin resistance by promoting glucose transporter 4 (GLUT4) expression and translocation in skeletal muscle of rats, there is no literature available regarding to the effect of type 1 of galanin receptors (GALR1) on insulin resistance in skeletal muscle of type 2 diabetic rats. Herein, we intended to survey the central effect of GALR1 agonist M617 on insulin resistance in skeletal muscle and its underlying mechanisms. We found that the intracerebroventricular injection of M617 increased glucose infusion rates in hyperinsulinemic euglycemic clamp tests, but attenuated the plasma insulin and glucose concentrations of diabetic rats. Furthermore, administration of M617 markedly increased GLUT4 mRNA expression and GLUT4 translocation in skeletal muscle of diabetic rats. Last, perfusion of M617 increased phosphorylated Akt and phosphorylated AS160 levels in the skeletal muscle of diabetic rats. In conclusion, central injection of M617 mitigated insulin resistance of skeletal muscle by enhancing GLUT4 translocation from intracellular pools to plasma membranes via the activation of the Akt/AS160/GLUT4 signaling pathway.

Dioscorea esculenta increase cytochrome c oxidase 1 expression and adenosine triphosphate in diabetic rats

BACKGROUND: The low cytochrome c oxidase (COX)-1 activity was associated with reduction of adenosin triphosphate (ATP) production in diabetes mellitus (DM) individuals. Interestingly, the secondary metabolite of Dioscorea esculenta (lesser yam) fermentation in gut can increase ATP production. OBJECTIVES: The aim of this study was to evaluate the effect of Lesser yam diet on ATP level and COX-1 expression in type 2 diabetic rats. METHODS: Thirty Wistar rats were divided into 5 groups: (1) normal rats (N), (2) diabetic rats (DM), (3) diabetic rats with lesser yam 200 mg/kg BW (DMT1), (4) diabetic rats with lesser yam 400 mg/kg BW (DMT2), (5) diabetic rats with lesser yam 800 mg/kg BW (DMT3). The diabetic rats were induced by nicotinamide and streptozotocin and had plasma glucose more than 126 mg/dL. ATP was measured before and after 4 weeks of intervention. COX-1-was determined at skeletal muscle, heart, liver, brown adipose tissue and kidney after intervention using immuno-histochemistry (IHC). RESULTS: Fasting blood glucose was reduced in all intervention groups compared to DM group (p = 0.016). ATP level was significantly increased in DMT1 group and slightly higher in DMT2 and DMT3 compared with the negative control (p > 0.05). After the intervention, COX-1 protein expression was higher in kidney, liver and skeletal muscle in diabetic rats received lesser yam compared to DM group (p < 0.05). CONCLUSION: In this study we found that lesser yam reduced fasting blood glucose, increase plasma ATP and expression of COX-1 protein.

Microvascular oxygen partial pressure during hyperbaric oxygen in diabetic rat skeletal muscle.

Hyperbaric oxygen (HBO) is a major therapeutic treatment for ischemic ulcerations that perforate skin and underlying muscle in diabetic patients. These lesions do not heal effectively, in part, because of the hypoxic microvascular O2 partial pressures (PmvO2 ) resulting from diabetes-induced cardiovascular dysfunction, which alters the dynamic balance between O2 delivery (Q̇o2) and utilization (V̇o2) rates. We tested the hypothesis that HBO in diabetic muscle would exacerbate the hyperoxic PmvO2 dynamics due, in part, to a reduction or slowing of the cardiovascular, sympathetic nervous, and respiratory system responses to acute HBO exposure. Adult male Wistar rats were divided randomly into diabetic (DIA: streptozotocin ip) and healthy (control) groups. A small animal hyperbaric chamber was pressurized with oxygen (100% O2) to 3.0 atmospheres absolute (ATA) at 0.2 ATA/min. Phosphorescence quenching techniques were used to measure PmvO2 in tibialis anterior muscle of anesthetized rats during HBO. Lumbar sympathetic nerve activity (LSNA), heart rate (HR), and respiratory rate (RR) were measured electrophysiologically. During the normobaric hyperoxia and HBO, DIA tibialis anterior PmvO2 increased faster (mean response time, CONT 78 ± 8, DIA 55 ± 8 s, P < 0.05) than CONT. Subsequently, PmvO2 remained elevated at similar levels in CONT and DIA muscles until normobaric normoxic recovery where the DIA PmvO2 retained its hyperoxic level longer than CONT. Sympathetic nervous system and cardiac and respiratory responses to HBO were slower in DIA vs. CONT. Specifically the mean response times for RR (CONT: 6 ± 1 s, DIA: 29 ± 4 s, P < 0.05), HR (CONT: 16 ± 1 s, DIA: 45 ± 5 s, P < 0.05), and LSNA (CONT: 140 ± 16 s, DIA: 247 ± 34 s, P < 0.05) were greater following HBO onset in DIA than CONT. HBO treatment increases tibialis anterior muscle PmvO2 more rapidly and for a longer duration in DIA than CONT, but not to a greater level. Whereas respiratory, cardiovascular, and LSNA responses to HBO are profoundly slowed in DIA, only the cardiovascular arm (via HR) may contribute to the muscle vascular incompetence and these faster PmvO2 kinetics.

Intracerebroventricular Injection of Alarin Increased Glucose Uptake in Skeletal Muscle of Diabetic Rats.

In order to investigate the central effect of alarin on glucose uptake, we administered alarin and/ or its inhibitor, ala6-25Cys into the cerebral ventricles of the type 2 diabetic rats. Then the relative parameters about glucose uptake in skeletal muscles were measured. We found that central treatment with alarin significantly increased the food intake, body weight and glucose infusion rates in hyperinsulinemic euglycemic clamp tests of the animals. Besides, the treatment also enhanced 2-deoxy-[3H]-D-glucose uptake, vesicle-associated membrane protein 2 contents, glucose transporter 4 protein and mRNA expression, as well as pAktThr308, pAktSer473 and total Akt levels in muscle cells, but reduced plasma glucose and insulin levels of the rats. All of the alarin-inducing events may be antagonised by central injection of ala6-25Cys. These results suggest that central administration of alarin stimulates glucose uptake mediated by activation of Akt signal pathway in type 2 diabetic animals.

Six-week anaerobic training improves proteolytic profile of diabetic rats.

To evaluate the effect of six-week anaerobic training on the mRNA expression of genes related to proteolysis Ubb (Ubiquitin), E2-14kDa, Trim63 (MuRF1 protein) and Nfkb1 in the skeletal muscle of diabetic rats. Four groups were established: DE (DiabetesExercised), DS (Diabetes Sedentary), CE (Control Exercised) and CS (Control Sedentary). The training consisted of 3 sets of 12 jumps in the liquid mean with load equivalent to 50% of BW for 6 weeks. Euthanasia occurred under ip anesthesia, and blood, adipose tissue and skeletal muscles were collected. Gene expression was quantified by RT-PCR in the gastrocnemius muscle. ANOVA one-way was used for comparison among groups, with post-hoc (Tukey) when necessary, considering p < 0.05. We observed reduction in the body weight and adipose tissue in the diabetic groups. The muscle mass was reduced in DS, which could be reversed by training (DE). Although DS and DE have presented similar body weight, the training protocol in DE promoted reduction in the adipose tissue, and increase of muscle mass. Anaerobic training was efficient to reduce glycaemia only in the diabetic animals until 6 hours after the end of training. The Trim63 gene expression was increased in DS; decreased Ubb gene level was observed in trained rats (CE and DE) compared to sedentary (CS and DS), and DE presented the lowest level of E2-14kDa gene expression. Six-week anaerobic training promoted muscle mass gain, improved glycemic control, and exerted inhibitory effect on the proteolysis of gastrocnemius muscle of diabetic rats.

CRTC2 Contributes to PGC‐1α Expression in Skeletal Muscle Cells

Muscle wasting associated with chronic diseases has been linked to decreased expression of the transcriptional coactivator PGC‐1α. Overexpression of PGC‐1α can reduce FoxO‐mediated atrogene expression and counter muscle loss. Previous reports indicate that PGC‐1α transcription is regulated by CREB in a process that requires CREB‐regulated transcription coactivator (CRTC2). We recently found that CRTC2 protein is reduced in skeletal muscle of diabetic rats whereas CREB is highly phosphorylated (i.e., activated). Nuclear translocation of CRTC2 is promoted by dephosphorylation via calcineurin (CnA) while nuclear export occurs by phosphorylation via the salt‐inducible kinases (SIK). Our experiments tested the hypothesis that glucocorticoids decrease PGC‐1α expression, in part, by reducing CRTC2 levels in the nucleus. L6 myotubes were treated ± dexamethasone (Dex, 100nM) for 48hrs. Dex decreased PGC‐1α protein and nuclear level of CRTC2. It also decreased nuclear CnA and increased nuclear SIK, supporting the observed reduction in nuclear CRTC2 levels. Over‐expression of CRTC2 increased PGC‐1α protein and mRNA levels. To assess the role of CRTC2 on PGC‐1α transcription, muscle cells were transfected with a PGC‐1α luciferase reporter plasmid (PGC‐1α‐Luc). Over‐expression of CRTC2 increased PGC‐1α‐Luc activity. Dex decreased PGC‐1α‐Luc activity and deletion of the CRE binding site from PGC‐1α‐Luc (PGC‐1α‐DCRE‐Luc) attenuated the response. These data support the interaction of CRTC2 with phospho‐CREB as a mechanism for increasing PGC‐1α expression. Reduced nuclear CRTC2 may contribute to the loss of muscle mass arising during chronic diseases associated with elevated glucocorticoids.Supported by NIH RO1 DK95610, NIH T32 DK007656 and VA Merit X01BX001456

Effects of oleanolic acid on the insulin signaling pathway in skeletal muscle of streptozotocin‐induced diabetic male Sprague‐Dawley rats

The pant-derived triterpene oleanolic acid (OA) has been shown to have antidiabetic effects, but its action on the insulin signaling cascade has not been fully elucidated. The aim of the present study was to investigate the effects of OA on aspects of the phosphatidylinositol 3-kinase/Akt insulin signaling cascade in skeletal muscle of streptozotocin-induced type 1 diabetic male Sprague-Dawley rats. Diabetic and non-diabetic rats were treated with insulin (4 IU/kg), OA (80 mg/kg), and the combination of OA + insulin in acute 60-min and sub-chronic 14-day studies. Single and daily doses were administered in the acute and sub-chronic studies, respectively. In acute studies, phosphorylated (p-) Akt and p-glycogen synthase (GS) expression was evaluated. In sub-chronic studies, GS and glycogen phosphorylase (GP) expression and activity were evaluated, as were glycogen levels. The findings show that OA enhances insulin-stimulated hypoglycemic effects in diabetic rats. In the acute study, OA increased levels of p-Akt and decreased levels of p-GS. In the sub-chronic study, OA increased both GS and GP activity, whereas OA + insulin increased GS and decreased GP activity. Treatment of rats with OA and OA + insulin increased GS expression in the skeletal muscle of diabetic rats and decreased GP expression. Glycogen levels were increased by OA but decreased OA + insulin treatment. Oleanolic acid in synergy with insulin can enhance activation of the insulin signaling pathway. Furthermore, the present study provides evidence of OA activation of insulin signaling enzymes independent of insulin.

Effects of Swimming Exercise on GLUTs, MCTs, LDH, and Caspase-3 Expression of Skeletal Muscle in Diabetic Rats

Effects of Swimming Exercise on GLUTs, MCTs, LDH, and Caspase-3 Expression of Skeletal Muscle in Diabetic Rats

β-Caryophyllene, a natural sesquiterpene, modulates carbohydrate metabolism in streptozotocin-induced diabetic rats

The study was designed to evaluate the antihyperglycemic effects of β-caryophyllene (BCP), a natural sesquiterpene from spices on streptozotocin (STZ) induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (40mg/kg b.w.) in adult male Wistar rats. Diabetic rats exhibited an increase in glucose and HbA1c with a significant fall in insulin and hemoglobin levels. Aberrations in carbohydrate metabolic enzymes were noticed in liver, kidney and skeletal muscle of diabetic rats. A fall in liver and skeletal muscle glycogen with alterations in glycogen synthase and phosphorylase activities was also observed. Oral administration of BCP in dose dependent manner and glibenclamide (600μg/kg b.w.), a standard oral hypoglycemic drug to diabetic rats for 45 days significantly decreased glucose with increased plasma insulin levels and ameliorated the altered activities of carbohydrate metabolic enzymes to near normal. The insulinotropic effect of BCP was supported by immunohistochemical studies. BCP at a dose of 200mg/kg b.w. exerted significant antidiabetic effects than other two doses (100 and 400mg/kg b.w.). We conclude that administration of BCP has beneficial effects in glucose homeostasis in diabetic rats.

Phosphodiesterase inhibition increases PGC‐1α in muscle cells (1102.32)

Muscle wasting associated with chronic diseases, such as type I diabetes (DM), can be countered by restoring the reduced expression of the transcriptional coactivator PGC‐1α. Previous reports indicate that PGC‐1α transcription can be regulated by CREB in a process that requires nuclear localization of CRTC (CREB‐regulated transcription coactivator). We recently found that CRTC protein is reduced in skeletal muscle of diabetic rats whereas CREB is highly phosphorylated (i.e., activated). Nuclear translocation of CTRC is promoted by dephosphorylation via calcineurin (CnA) whereas nuclear export occurs by phosphorylation via the salt‐inducible kinases (SIK). Inhibition of phosphodiesterases (PDE), which raise cyclic AMP (cAMP) levels, results in increased PGC‐1α mRNA expression. cAMP also inhibits SIK suggesting this pathway may contribute to CRTC localization and thus PGC‐1α activity. Our experiments tested the hypothesis that inhibition of PDE increases the amount of nuclear CRTC and PGC‐1α transcription. Myotubes were transfected with luciferase reporter plasmids (Luc) and treated with the general PDE inhibitor IBMX (250uM) for 6 hours. IBMX increased PGC‐1α‐Luc promoter activity as well as the transcriptional activity of CREB. Deletion of the CRE site in PGC‐1α‐Luc prevents the increase in luciferase activity suggesting IBMX increases PGC‐1α activity via CREB. In addition, protein analysis indicates IBMX increases the level of nuclear CRTC. Together, these data imply that raising cAMP levels by inhibiting PDEs results in increased PGC‐1α transcriptional activity by a mechanism involving CREB and its coactivator, CRTC.Grant Funding Source: Supported by NIH RO1 DK95610, NIH T32 DK007656 and VA Merit X01BX001456

Jiaotai pill (交泰丸) enhances insulin signaling through phosphatidylinositol 3-kinase pathway in skeletal muscle of diabetic rats

To investigate the effect of Jiaotai Pill (, JTP) at different constitutional proportions on insulin signaling through phosphatidylinositol 3-kinase (PI3K) pathway in the skeletal muscle of diabetic rats. The rat model of type 2 diabetes mellitus (T2DM) was established by intravenous injection of a small dose of streptozotoein plus high fat diet feeding. JTP at the same dosage of cinnamon and the increasing dosage of Coptis chinensis was administered to diabetic rats for nine weeks respectively. Plasma glucose and insulin levels were assayed. The expressions of proteins were determined by Western blot method. All the three formulations of JTP decreased plasma glucose and fasting insulin levels as well as increased the protein expressions of insulin receptor β (InsRβ) subunit, insulin receptor substrate-1 (IRS-1), PI3K p85 subunit and glucose transporter 4 (GLUT4) in skeletal muscle. Meanwhile, JTP increased the tyrosine phosphorylation of InsRβ subunit and IRS-1, and reduced the serine phosphorylation of IRS-1 in skeletal muscle. Interestingly, the effect of JTP on improving insulin sensitivity was not dose-dependent. In contrast, JTP containing the least amount of Coptis chinensis exhibited the best effect. JTP at different constitutional proportions attenuates the development of diabetes in a rat model of T2DM. The mechanism might be associated with enhancing insulin signaling through PI3K pathway in the skeletal muscle.

Lipoic acid ameliorates apoptosis in alloxan-induced diabetic rat skeletal muscle

Oxidant increase has been suggested to play a critical role in the progression and pathogenesis of diabetes and its complications, including the loss of skeletal muscle. However, the exact molecular mechanism responsible for the loss of skeletal muscle mass during diabetes is unclear. Since oxidative stress and muscle mitochondrial dysfunction are known to be major components in the induction of apoptosis as well as insulin resistance, we investigated the occurrence of apoptosis in diabetic rat skeletal muscle. Increased oxidants associated with diabetes results in the translocation of mitochondrial-cytochrome c into the cytosol. The enhanced outer mitochondrial membrane permeability accompanied with loss of mitochondrial transmembrane potential may be attributed to the loss of mitochondrial-cytochrome c content. This, in turn, led to the activation of caspase cascade and apoptosis, as evident from evaluated caspase-3 levels and DNA fragmentation, in skeletal muscle of diabetic rats. Oral supplementation of lipoic acid normalized these changes to that of control rats, possibly by enhancing the redox status and by the maintenance of mitochondrial membrane integrity. The maintenance of mitochondrial membrane integrity and the observed decrease in pro-/anti-apoptotic factor ratio, cytosolic cytochrome c content and caspase-3 levels by lipoic acid suggested that lipoic acid supplementation could be beneficial in ameliorating oxidative stress mediated apoptosis during diabetes.

Correction: Glutamine Supplementation Stimulates Protein-Synthetic and Inhibits Protein-Degradative Signaling Pathways in Skeletal Muscle of Diabetic Rats

Correction: Glutamine Supplementation Stimulates Protein-Synthetic and Inhibits Protein-Degradative Signaling Pathways in Skeletal Muscle of Diabetic Rats

Exercise-induced changes of MCT1 in cardiac and skeletal muscles of diabetic rats induced by high-fat diet and STZ

We hypothesized that a part of therapeutic effects of endurance training on insulin resistance is mediated by increase in cardiac and skeletal muscle mitochondrial lactate transporter, monocarboxylate transporter 1 (MCT1). Therefore, we examined the effect of 7 weeks endurance training on the mRNA and protein expression of MCT1 and MCT4 and their chaperon, CD147, on both sarcolemmal and mitochondrial membrane, separately, in healthy and type 2 diabetic rats. Diabetes was induced by injection of low dose of streptozotocin and feeding with high-fat diet. Insulin resistance was confirmed by homeostasis model assessment-estimated insulin resistance index and accuracy of two membranes separation was confirmed by negative control markers (glucose transporter 1 and cytochrome c oxidase. Real-time PCR and western blotting were used for mRNA and protein expression, respectively. Diabetes dramatically reduced MCT1 and MCT4 mRNA and their expression on sarcolemmal membrane whereas the reduction in MCT1 expression was less in mitochondrial membrane. Training increased the MCT1 mRNA and protein expression in both membranes and decreased insulin resistance as an adaptive consequence. In both tissues increase in CD147 mRNA was only parallel to MCT1 expression. The response of MCT1 on sarcolemmal and mitochondrial membranes was different between cardiac and skeletal muscles which indicate that intracellular lactate kinetic is tissue specific that allows a tissue to coordinate whole organism metabolism.

Effect of iridoid glucoside on plasma lipid profile, tissue fatty acid changes, inflammatory cytokines, and GLUT4 expression in skeletal muscle of streptozotocin-induced diabetic rats

The present study was designed to examine the antihyperlipidaemic potential of iridoid glucoside isolated from Vitex negundo leaves in STZ-induced diabetic rats. The levels of cholesterol (TC), triglycerides, lipoproteins, free fatty acids, phospholipids, fatty acid composition, proinflammatory cytokines, muscle glycogen content, and glucose transporter 4 (GLUT4) expression were estimated in control and diabetic rats. Oral administration of iridoid glucoside at a dose of 50 mg/kg body weight per day to STZ-induced diabetic rats for a period of 30 days resulted in a significant reduction in plasma and tissue (liver and kidney) cholesterol, triglycerides, free fatty acids, and phospholipids. In addition, the decreased plasma levels of high-density lipoprotein-cholesterol and increased plasma levels of low density lipoprotein- and very low density lipoprotein-cholesterol in diabetic rats were restored to near normal levels following treatment with iridoid glucoside. The fatty acid composition of the liver and kidney was analyzed by gas chromatography. The altered fatty acid composition in the liver and kidney of diabetic rats was also restored upon treatment with iridoid glucoside. Moreover, the elevated plasma levels of proinflammatory cytokines and decreased levels of muscle glycogen and GLUT4 expression in the skeletal muscle of diabetic rats were reinstated to their normal levels via enhanced secretion of insulin from the remnant β cells of pancreas by the administration of iridoid glucoside. The effect produced by iridoid glucoside on various parameters was comparable with that of glibenclamide, a well-known antihyperglycemic drug.

Glutamine supplementation stimulates protein-synthetic and inhibits protein-degradative signaling pathways in skeletal muscle of diabetic rats.

In this study, we investigated the effect of glutamine (Gln) supplementation on the signaling pathways regulating protein synthesis and protein degradation in the skeletal muscle of rats with streptozotocin (STZ)-induced diabetes. The expression levels of key regulatory proteins in the synthetic pathways (Akt, mTOR, GSK3 and 4E-BP1) and the degradation pathways (MuRF-1 and MAFbx) were determined using real-time PCR and Western blotting in four groups of male Wistar rats; 1) control, non-supplemented with glutamine; 2) control, supplemented with glutamine; 3) diabetic, non-supplemented with glutamine; and 4) diabetic, supplemented with glutamine. Diabetes was induced by the intravenous injection of 65 mg/kg bw STZ in citrate buffer (pH 4.2); the non-diabetic controls received only citrate buffer. After 48 hours, diabetes was confirmed in the STZ-treated animals by the determination of blood glucose levels above 200 mg/dL. Starting on that day, a solution of 1 g/kg bw Gln in phosphate buffered saline (PBS) was administered daily via gavage for 15 days to groups 2 and 4. Groups 1 and 3 received only PBS for the same duration. The rats were euthanized, and the soleus muscles were removed and homogenized in extraction buffer for the subsequent measurement of protein and mRNA levels. The results demonstrated a significant decrease in the muscle Gln content in the diabetic rats, and this level increased toward the control value in the diabetic rats receiving Gln. In addition, the diabetic rats exhibited a reduced mRNA expression of regulatory proteins in the protein synthesis pathway and increased expression of those associated with protein degradation. A reduction in the skeletal muscle mass in the diabetic rats was observed and was alleviated partially with Gln supplementation. The data suggest that glutamine supplementation is potentially useful for slowing the progression of muscle atrophy in patients with diabetes.

Grape seed proanthocyanidin extracts alleviate oxidative stress and ER stress in skeletal muscle of low‐dose streptozotocin‐ and high‐carbohydrate/high‐fat diet‐induced diabetic rats

Although ER stress in pancreas, liver, and adipose tissue was reported to be a novel event linked to the pathogenesis of type 2 diabetes mellitus, there is much less information on this event in skeletal muscle. Some studies indicated that treatment with antioxidants had beneficial effects on ER stress and diabetes. This study focuses on the effects of a strong antioxidant, grape seed proanthocyanidin extracts (GSPE), on skeletal muscle in diabetic rats induced with low dose streptozotocin- and a high-carbohydrate/high-fat diet. After 16 wk of GSPE treatment, diabetic rats showed decreased plasma glucose levels and insulin resistance. The efficacious effect of GSPE was manifested by the amelioration of muscular damage and dysfunction, as observed by histological examination and periodic acid Schiff staining. Concurrently, calcium overload and the abnormal activities of antioxidant enzymes and ATPases in diabetic muscles were partially reversed by GSPE treatment. GSPE also increased the activity of protein kinase B (a mediator of insulin's metabolic action) and partially alleviated severe ER stress. These findings suggest that GSPE may have auxiliary therapeutic potential for type 2 diabetes mellitus by decreasing oxidative stress and ER stress in skeletal muscle.

The Impact of Magnesium on Isometric Twitch Parameters and Resting Membrane Potential of the Skeletal Muscle in Diabetic Rats

To present the relationship between oral magnesium supplementation, blood glucose, and changes in isometric twitch parameters, resting membrane potential (RMP), in the gastrocnemius muscle in diabetic rats. Sixty rats were used in this study. The rats were divided into four groups: control (drinking tap water, Group I, n = 15), control with treated with magnesium sulfate (10 g/L) (Group II, n = 15), diabetic (Group III, n = 15), and diabetic with treated with magnesium sulfate (10 g/L) (Group IV, n = 15). In Group II and IV, the level of plasma magnesium was increased comparing to those of the control group (p < 0.05). Isometric twitch tensions were decreased significantly in the Group III, but Group IV isometric twitch tensions were increased significantly. Group IV RMP values were close to the Group I. Hyperglycemia decreases gastrocnemius muscle isometric twitch tension and increases RMP in diabetic rats. Magnesium treatment can prevent these diabetic complications.

Curcuminoids exert glucose‐lowering effect in type 2 diabetes by decreasing serum free fatty acids: a double‐blind, placebo‐controlled trial

We previously found that curcuminoids decreased blood glucose and improved insulin resistance by reducing serum free fatty acids (FFAs) and increasing fatty acid oxidation in skeletal muscle of diabetic rats. This study was to investigate whether curcuminoids have beneficial effects on type 2 diabetic patients, and its possible mechanisms. Overweight/obese type 2 diabetic patients (BMI ≥ 24.0; fasting blood glucose ≥ 7.0 mmol/L or postprandial blood glucose ≥11.1 mmol/L) were randomly assigned to curcuminoids (300 mg/day) or placebo for 3 months. Bodyweight, glycosylated hemoglobin A1c (HbA1c ,% ), serum fasting glucose, FFAs, lipids, and lipoprotein lipase (LPL) were determined. A total of 100 patients (curcuminoids, n = 50; placebo, n = 50) completed the trial. Curcuminoids supplementation significantly decreased fasting blood glucose (p < 0.01), HbA1c (p = 0.031), and insulin resistance index (HOMA-IR) (p < 0.01) in type 2 diabetic patients. Curcuminoids also led to a significant decrease in serum total FFAs (p < 0.01), triglycerides (P = 0.018), an increase in LPL activity (p < 0.01). These findings suggest a glucose-lowering effect of curcuminoids in type 2 diabetes, which is partially due to decrease in serum FFAs, which may result from promoting fatty acid oxidation and utilization.