The Effect of Lower Limb Combined Neuromuscular Electrical Stimulation on Skeletal Muscle Signaling for Glucose Utilization, Myofiber Distribution, and Metabolic Function after Spinal Cord Injury.

Maintaining healthy myofiber type and metabolic function early after spinal cord injury (SCI) may prevent chronic metabolic disorders. This study compares the effects of a 2-5 week combined (aerobic + resistance) neuromuscular electrical stimulation (Comb-NMES) regimen versus a sham control treatment on muscle protein signaling for glucose uptake, myofiber type distribution, and metabolic function. Twenty participants (31 ± 9 years of age) with an SCI (C4-L1, AIS level A-C) within 14 days of the SCI were randomly assigned to control (N = 8) or Comb-NMES (N = 12). Sessions were given three times per week. Fasting blood samples and vastus lateralis muscle biopsies were collected 24-48 h before or after the last session. Western blots were performed to quantify proteins, immunohistochemical analyses determined muscle myofiber distribution, and enzymatic assays were performed to measure serum glucose, insulin, and lipids. Our main findings include a decrease in fasting glucose (p < 0.05) and LDL-C (p < 0.05) levels, an upregulation of CamKII and Hexokinase (p < 0.05), and an increase in type I (+9%) and a decrease in type IIx (-36%) myofiber distribution in response to Comb-NMES. Our findings suggest that maintaining healthy myofiber type and metabolic function may be achieved via early utilization of Comb-NMES.

Two isoprenylated flavonoids from Dorstenia psilurus activate AMPK, stimulate glucose uptake, inhibit glucose production and lower glycemia.

Root extracts of a Cameroon medicinal plant, Dorstenia psilurus, were purified by screening for AMP-activated protein kinase (AMPK) activation in incubated mouse embryo fibroblasts (MEFs). Two isoprenylated flavones that activated AMPK were isolated. Compound 1 was identified as artelasticin by high-resolution electrospray ionization mass spectrometry and 2D-NMR while its structural isomer, compound 2, was isolated for the first time and differed only by the position of one double bond on one isoprenyl substituent. Treatment of MEFs with purified compound 1 or compound 2 led to rapid and robust AMPK activation at low micromolar concentrations and increased the intracellular AMP:ATP ratio. In oxygen consumption experiments on isolated rat liver mitochondria, compound 1 and compound 2 inhibited complex II of the electron transport chain and in freeze-thawed mitochondria succinate dehydrogenase was inhibited. In incubated rat skeletal muscles, both compounds activated AMPK and stimulated glucose uptake. Moreover, these effects were lost in muscles pre-incubated with AMPK inhibitor SBI-0206965, suggesting AMPK dependency. Incubation of mouse hepatocytes with compound 1 or compound 2 led to AMPK activation, but glucose production was decreased in hepatocytes from both wild-type and AMPKß1-/- mice, suggesting that this effect was not AMPK-dependent. However, when administered intraperitoneally to high-fat diet-induced insulin-resistant mice, compound 1 and compound 2 had blood glucose-lowering effects. In addition, compound 1 and compound 2 reduced the viability of several human cancer cells in culture. The flavonoids we have identified could be a starting point for the development of new drugs to treat type 2 diabetes.

Maltitol inhibits small intestinal glucose absorption and increases insulin mediated muscle glucose uptake ex vivo but not in normal and type 2 diabetic rats.

This study investigated the effects of maltitol on intestinal glucose absorption and muscle glucose uptake using ex vivo and in vivo experimental models. The ex vivo experiment was conducted in isolated jejunum and psoas muscle from normal rats. The in vivo study investigated the effects of a single bolus dose of maltitol on gastric emptying, intestinal glucose absorption and digesta transit in normal and type 2 diabetic rats. Maltitol inhibited glucose absorption in isolated rat jejunum and increased glucose uptake in isolated rat psoas muscle in the presence of insulin but not in the absence of insulin. In contrast, maltitol did not significantly (p > 0.05) alter small intestinal glucose absorption or blood glucose levels as well as gastric emptying and digesta transit in normal or type 2 diabetic rats. The results suggest that maltitol may not be a suitable dietary supplement for anti-diabetic food and food products to improve glycemic control.

Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study.

The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC50 = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU50 = 2.68 ± 0.75 %) or without (GU50 = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.

Effects of Korean red ginseng supplementation on muscle glucose uptake in high-fat fed rats.

It has been recognized that ginseng has anti-diabetic effects in skeletal muscle, but the mechanism has not been intensively investigated. The aim of this study was to investigate the effects of Korean red ginseng (Panax ginseng) supplementation on muscle glucose uptake in high-fat fed rats. Sixteen rats were randomly divided into two groups: a control group (CON, n = 8) and a Korean red ginseng group (KRG, n = 8). The KRG group ingested RG extract (1 g·kg(-1), 6 days/week) mixed in water for two weeks. After the two-week treatment, plasma lipid profiles, and glucose and insulin concentrations were measured. The triglyceride (TG) and glucose transporter 4 (GLUT-4) contents were measured in the skeletal muscle and liver. The rate of glucose transport was determined under a submaximal insulin concentration during muscle incubation. Plasma FFA concentrations were significantly decreased in KRG (P < 0.05). Liver and muscle triglyceride concentrations were also decreased in the KRG treatment group (P < 0.05) compared to the CON group. In addition, resting plasma insulin and glucose levels were significantly lower after Korean red ginseng treatment (P < 0.05). However, muscle glucose uptake was not affected by Korean red ginseng treatment, as evidenced by the rate of glucose transport in the epitorchealis muscle under submaximal insulin concentrations. These results suggest that while KRG supplementation could improve whole body insulin resistance and plasma lipid profiles, it is unlikely to have an effect on the insulin resistance of skeletal muscle, which is the major tissue responsible for plasma glucose handling.

Effects of Korean red ginseng supplementation on muscle glucose uptake in high-fat fed rats / 中国天然药物

It has been recognized that ginseng has anti-diabetic effects in skeletal muscle, but the mechanism has not been intensively investigated. The aim of this study was to investigate the effects of Korean red ginseng (Panax ginseng) supplementation on muscle glucose uptake in high-fat fed rats. Sixteen rats were randomly divided into two groups: a control group (CON, n = 8) and a Korean red ginseng group (KRG, n = 8). The KRG group ingested RG extract (1 g·kg(-1), 6 days/week) mixed in water for two weeks. After the two-week treatment, plasma lipid profiles, and glucose and insulin concentrations were measured. The triglyceride (TG) and glucose transporter 4 (GLUT-4) contents were measured in the skeletal muscle and liver. The rate of glucose transport was determined under a submaximal insulin concentration during muscle incubation. Plasma FFA concentrations were significantly decreased in KRG (P < 0.05). Liver and muscle triglyceride concentrations were also decreased in the KRG treatment group (P < 0.05) compared to the CON group. In addition, resting plasma insulin and glucose levels were significantly lower after Korean red ginseng treatment (P < 0.05). However, muscle glucose uptake was not affected by Korean red ginseng treatment, as evidenced by the rate of glucose transport in the epitorchealis muscle under submaximal insulin concentrations. These results suggest that while KRG supplementation could improve whole body insulin resistance and plasma lipid profiles, it is unlikely to have an effect on the insulin resistance of skeletal muscle, which is the major tissue responsible for plasma glucose handling.