Carbohydrate, protein, and carbohydrate-protein supplements were compared to determine their effects on muscle glycogen storage during recovery from prolonged exhaustive exercise. Nine male subjects cycled for 2 h on three separate occasions to deplete their muscle glycogen stores. Immediately and 2 h after each exercise bout, they ingested 112.0 g carbohydrate (CHO), 40.7 g protein (PRO), or 112.0 g carbohydrate and 40.7 g protein (CHO-PRO). Blood samples were drawn before exercise, immediately after exercise, and throughout recovery. Muscle biopsies were taken from the vastus lateralis immediately and 4 h after exercise. During recovery the plasma glucose response of the CHO treatment was significantly greater than that of the CHO-PRO treatment, but the plasma insulin response of the CHO-PRO treatment was significantly greater than that of the CHO treatment. Both the CHO and CHO-PRO treatments produced plasma glucose and insulin responses that were greater than those produced by the PRO treatment (P less than 0.05). The rate of muscle glycogen storage during the CHO-PRO treatment [35.5 +/- 3.3 (SE) mumol.g protein-1.h-1] was significantly faster than during the CHO treatment (25.6 +/- 2.3 mumol.g protein-1.h-1), which was significantly faster than during the PRO treatment (7.6 +/- 1.4 mumol.g protein-1.h-1). The results suggest that postexercise muscle glycogen storage can be enhanced with a carbohydrate-protein supplement as a result of the interaction of carbohydrate and protein on insulin secretion.

Our laboratory recently reported that chronic resistance training (RT) improved insulin-stimulated glucose transport in normal rodent skeletal muscle, owing, in part, to increased GLUT-4 protein concentration (Yaspelkis BB III, Singh MK, Trevino B, Krisan AD, and Collins DE. Acta Physiol Scand 175: 315-323, 2002). However, it remained to be determined whether these improvements resulted from alterations in the insulin signaling cascade as well. In addition, the possibility existed that RT might improve skeletal muscle insulin resistance. Thirty-two male Sprague-Dawley rats were assigned to four groups: control diet (Con)-sedentary (Sed); Con-RT; high-fat diet (HF)-Sed; and HF-RT. Animals consumed their respective diets for 9 wk; then RT animals performed 12 wk of training (3 sets, 10 repetitions at 75% one-repetition maximum, 3x/wk). Animals remained on their dietary treatments over the 12-wk period. After the training period, animals were subjected to hindlimb perfusions. Insulin-stimulated insulin receptor substrate-1-associated phosphatidylinositol-3 kinase activity was enhanced in the red gastrocnemius and quadriceps of Con-RT and HF-RT animals. Atypical PKC-zeta/lambda and Akt activities were reduced in HF-Sed and normalized in HF-RT animals. Resistance training increased GLUT-4 protein concentration in red gastrocnemius and quadriceps of Con-RT and HF-RT animals. No differences were observed in total protein concentrations of insulin receptor substrate-1, Akt, atypical PKC-zeta/lambda, or phosphorylation of Akt. Collectively, these findings suggest that resistance training increases insulin-stimulated carbohydrate metabolism in normal skeletal muscle and reverses high-fat diet-induced skeletal muscle insulin resistance by altering components of both the insulin signaling cascade and glucose transporter effector system.

Both pharmacological intervention (i.e., thiazolidinediones [TZDs]) and lifestyle modification (i.e., exercise training) are clinically effective treatments for improving whole-body insulin sensitivity. However, the mechanism(s) by which these therapies reverse lipid-induced insulin resistance in skeletal muscle is unclear. We determined the effects of 4 weeks of rosiglitazone treatment and exercise training and their combined actions (rosiglitazone treatment and exercise training) on lipid and glucose metabolism in high-fat-fed rats. High-fat feeding resulted in decreased muscle insulin sensitivity, which was associated with increased rates of palmitate uptake and the accumulation of the fatty acid metabolites ceramide and diacylglycerol. Impairments in lipid metabolism were accompanied by defects in the Akt/AS160 signaling pathway. Exercise training, but not rosiglitazone treatment, reversed these impairments, resulting in improved insulinstimulated glucose transport and increased rates of fatty acid oxidation in skeletal muscle. The improvements to glucose and lipid metabolism observed with exercise training were associated with increased AMP-activated protein kinase ␣1 activity; increased expression of Akt1, peroxisome proliferator-activated receptor ␥ coactivator 1, and GLUT4; and a decrease in AS160 expression. In contrast, rosiglitazone treatment exacerbated lipid accumulation and decreased insulin-stimulated glucose transport in skeletal muscle. However, rosiglitazone, but not exercise training, increased adipose tissue GLUT4 and acetyl CoA carboxylase expression. Both exercise training and rosiglitazone decreased liver triacylglycerol content. Although both interventions can improve whole-body insulin sensitivity, our results show that they produce divergent effects on protein expression and triglyceride storage in different tissues. Accordingly, exercise training and rosiglitazone may act as complementary therapies for the treatment of insulin resistance.

The rates of muscle glucose uptake of trained (TR) and untrained (UT) obese Zucker rats were assessed by hindlimb perfusion under basal conditions (no insulin) in the presence of a maximally stimulating concentration of insulin (10 mU/ml) and after muscle contraction elicited by electrical stimulation of the sciatic nerve. Perfusate contained 28 mM glucose and 7.5 microCi/mmol of 2-deoxy-D-[3H]glucose. Muscle GLUT-4 concentration was determined by Western blot analysis and expressed as a percentage of a heart standard. The rates of insulin-stimulated glucose uptake were significantly higher in the plantaris, red gastrocnemius (RG), and white gastrocnemius (WG), but not the soleus or extensor digatorum longus (EDL) of TR compared with UT rats. After muscle contraction the rates of glucose uptake in the TR rats were significantly higher in the soleus, plantaris, and RG. TR rats had significantly higher GLUT-4 protein concentration and citrate synthase activity than the UT rats in the soleus, plantaris, RG, and WG. Basal plasma membrane GLUT-4 protein concentration of TR rats was 144% above UT rats (P < 0.01). Stimulation by insulin and contraction resulted in a significant increase in plasma membrane GLUT-4 protein concentration in UT rats only. However, plasma membrane GLUT-4 protein concentration in insulin- and contraction-stimulated TR rats remained 53% and 30% greater than that of UT rats, respectively (P < 0.05). Exercise training did not alter basal, insulin-, or contraction-stimulated GLUT-4 functional activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Leptin administration improves skeletal muscle insulin responsiveness in diet-induced insulin-resistant rats. Am J Physiol Endocrinol Metab 280: E130-E142, 2001.-In addition to suppressing appetite, leptin may also modulate insulin secretion and action. Leptin was administered here to insulin-resistant rats to determine its effects on secretagogue-stimulated insulin release, whole body glucose disposal, and insulin-stimulated skeletal muscle glucose uptake and transport. Male Wistar rats were fed either a normal (Con) or a high-fat (HF) diet for 3 or 6 mo. HF rats were then treated with either vehicle (HF), leptin (HF-Lep, 10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 sc), or food restriction (HF-FR) for 12-15 days. Glucose tolerance and skeletal muscle glucose uptake and transport were significantly impaired in HF compared with Con. Whole body glucose tolerance and rates of insulinstimulated skeletal muscle glucose uptake and transport in HF-Lep were similar to those of Con and greater than those of HF and HF-FR. The insulin secretory response to either glucose or tolbutamide (a pancreatic ␤-cell secretagogue) was not significantly diminished in HF-Lep. Total and plasma membrane skeletal muscle GLUT-4 protein concentrations were similar in Con and HF-Lep and greater than those in HF and HF-FR. The findings suggest that chronic leptin administration reversed a high-fat diet-induced insulin-resistant state, without compromising insulin secretion.ob gene product; high-fat diet; glucose tolerance; glucose uptake and transport; GLUT-4 protein LEPTIN, THE PRODUCT of the ob gene (62), has received a great deal of attention since its discovery in 1994, due to the ability of this 16-kDa protein hormone to reduce visceral adipose deposition (21,37). This biological activity is important from a public health perspective, as increases in visceral fat have been associated with "insulin resistance syndrome" or Syndrome X (39). Attenuation of insulin resistance will decrease the incidence of metabolic abnormalities such as hypertriglyceridemia, reduced high-density lipoproteins, elevated apolipoprotein B levels, and hypertension. Furthermore, reduced visceral fat deposition may also prevent the development of non-insulin-dependent diabetes (17).It is believed that leptin exerts its primary effect by acting on receptors in the hypothalamus, possibly via inhibition of neuropeptide Y release (47). However, leptin receptor isoforms are expressed in tissues other than the hypothalamus (12, 29, 51), and insulin action (e.g., phosphatidylinositol 3-kinase activity, skeletal muscle glucose uptake and transport) is improved in these tissues after leptin treatment (3,56,57,60). Improvements in insulin-stimulated glucose disposal after chronic leptin administration were initially demonstrated by Barzilai et al. (3) and Sivitz et al. (44). Barzilai et al. (3) reported that 8 days of leptin treatment increased whole body glucose uptake in SpragueDawley rats as assessed by the euglycemic clamp technique. In an extension to these findings, we (60) found that 14...