Insulin treatment normalizes decreased glucose transport capacity in streptozotocin-diabetic rat muscle.
Explore the source record for details and available documents.
3-O-Methylglucose↗
Biomedical subjects
H Wallberg-Henriksson
Publications and source records attributed to H Wallberg-Henriksson.
Effect of catecholamines on glucose uptake and glycogenolysis in rat skeletal muscle.
The effect of catecholamines on glycogenolysis and sugar transport was evaluated in rat epitrochlearis (fast-twitch) and soleus (slow-twitch) muscles in vitro. When muscles were incubated with 0.1 microM epinephrine (both an alpha- and beta-agonist), the proportion of phosphorylase in the a form increased from 6.2 +/- 0.7 to 37.4 +/- 5.7% in epitrochlearis muscle and from 9.1 +/- 0.7 to 21.6 +/- 1.3% in soleus muscle. Both the activation of phosphorylase and the resulting glycogenolysis could be prevented by preincubation with the beta-blocker, propranolol. The effect of catecholamines on the rate of sugar transport was also examined in epitrochlearis muscle. The beta-agonist, isoproterenol, significantly depressed the rate of 3-O-methylglucose uptake, while the alpha-agonist, phenylephrine, had no effect. Inclusion of 0.1% albumin in the incubation medium increased the resting rate of sugar transport twofold. When isoproterenol + albumin were present, rather than exerting a depressive effect the catecholamine further increased the rate of sugar uptake. This increase was prevented by preincubation with propranolol. It was concluded that glycogenolysis and sugar transport in rat skeletal muscle are solely under beta-adrenergic control.
Animals↗
Activation of glucose transport in diabetic muscle: responses to contraction and insulin.
The purpose of this study was to evaluate the effect of insulin deficiency on the ability of muscle contraction to activate glucose transport. Rats were made severely diabetic by injection of streptozotocin (SZ; 125 mg/kg body wt). Only those diabetic rats in which plasma insulin was too low to measure 3 days after SZ injection were included in this study. Glucose transport activity was evaluated by measuring 3-O-methylglucose uptake in epitrochlearis muscles in vitro. Contractile activity induced a 2.8-fold increase in 3-O-methylglucose uptake rate in epitrochlearis muscles of diabetic rats (P less than 0.01) even after the muscles had been thoroughly washed to remove any traces of insulin remaining in the extracellular fluid. However, this increase in sugar uptake was less than 50% as great as that seen in normal controls. This reduced ability to activate glucose transport was not limited to the effect of contractile activity, as the increase in sugar uptake rate in response to a maximal concentration of insulin was similarly reduced in the diabetic muscles. Thus it appears that contractile activity can accelerate glucose transport in insulin-deficient muscle; however, the maximal capacity to activate glucose transport is decreased in skeletal muscle after sustained insulin deficiency.
3-O-Methylglucose↗
Contractile activity increases glucose uptake by muscle in severely diabetic rats.
Muscle contractile activity is associated with an acceleration of glucose transport into muscle. It has been reported that the acceleration of glucose uptake by contractile activity in perfused rat muscles requires the presence of insulin in the perfusate. This claim was investigated using the perfused rat hindlimb preparation in the present study. Rats were made diabetic by injection of 125 mg/kg of streptozotocin and either studied 72 h later or maintained on insulin for 2 wk and then studied 3 days after cessation of insulin therapy. Only rats with plasma insulin levels too low to measure were used. The hindlimbs were washed out with 630 ml of medium over 75 min using a single flow-through washout before muscle stimulation. Despite the absence of insulin in the perfusion medium, stimulation of muscle contraction resulted in large increases in glucose uptake in both the diabetic and control rats. These findings do not support the claim that the stimulatory effect of muscle contraction on glucose uptake by perfused rat muscles requires the presence of insulin.
Animals↗
Influence of physical training on formation of muscle capillaries in type I diabetes.
The effects of physical training on skeletal muscle morphology and enzyme activities were compared in 10 male, type I diabetic subjects and 10 healthy, male, control subjects. The training program consisted of running for 45 min, three times per week for 8 wk. Muscle biopsies were obtained before and after the training period from the lateral portion of the gastrocnemius muscle. Pretraining maximal oxygen uptake was similar in the two groups (diabetic subjects 42 +/- 1 versus control subjects 43 +/- 2 ml X kg-1 X min-1), and the training resulted in an identical increase (+ 13%, P less than 0.01). Muscle capillarization (number of capillaries per muscle fiber) increased on the average in the control group (+ 14 +/- 4%, P less than 0.01), but was unchanged in the diabetic group (0 +/- 4%). Capillary density, expressed as number of capillaries per unit muscle cross sectional area, also increased on the average in controls (8 +/- 4%, P less than 0.05) but failed to do so in the diabetic patients (-8 +/- 6%, NS). The activities of the mitochondrial enzymes citrate synthase (+ 26-27%, P less than 0.01-0.05) and succinate dehydrogenase (+ 24-25%, P less than 0.05) increased significantly and similarly in the two groups, whereas training did not result in significant changes in the activities of the glycolytic enzymes 6-phosphofructokinase and glyceraldehyde-phosphate dehydrogenase. Glycemic control in the diabetic group did not improve with the training, as evaluated from hemoglobin A1 and home-monitored blood glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Increased peripheral insulin sensitivity and muscle mitochondrial enzymes but unchanged blood glucose control in type I diabetics after physical training.
Nine male, insulin-dependent diabetic patients participated in a 16-wk training program consisting of 1 h of jogging, running, ball games, and gymnastics, performed 2-3 times/wk. The training resulted in an 8% increase of maximal oxygen uptake (P less than 0.01). Insulin sensitivity as determined by the insulin clamp technique increased 20% (P less than 0.05). Glycosylated hemoglobin showed no change (10.4 +/- 0.7% versus 11.3 +/- 0.5%), 24-h urinary glucose excretion was not reduced, and home-monitored urine tests were unchanged. The frequency of hypoglycemic attacks did not change during the training period and body weight remained constant. There was a 14% fall in plasma cholesterol (P less than 0.01) and a rise in the proportion of HDL-cholesterol from 24 +/- 2% to 30 +/- 3% (P less than 0.01). Thigh muscle oxidative capacity increased, as indicated by a 24% increase in succinate dehydrogenase activity (P less than 0.05). The number of capillaries/muscle fiber increased 15% (P less than 0.01). However, as the mean muscle fiber cross-sectional area increased to a similar extent (11%, P less than 0.05), capillary density (cap x mm-2) was unchanged. In conclusion, this study demonstrates that physical training in insulin-dependent diabetics results in increased peripheral insulin sensitivity, a rise in muscle mitochondrial enzyme activities, decreased total plasma cholesterol levels, and unchanged blood glucose control. The findings suggest that in the absence of efforts to alter dietary regulation and insulin administration, physical training consisting of 2-3 weekly bouts of moderate exercise may not of itself improve blood glucose control in type I diabetes.
Adult↗
GLUT4: a key player regulating glucose homeostasis? Insights from transgenic and knockout mice (review).
Studies in which GLUT4 has been overexpressed in transgenic mice provide definitive evidence that glucose transport is rate limiting for muscle glucose disposal. Transgenic overexpression of GLUT4 selectively in skeletal muscle results in increased whole body glucose uptake and improves glucose homeostasis. These studies strengthen the hypothesis that the level of muscle GLUT4 affects the rate of whole body glucose disposal, and underscore the importance of GLUT4 in skeletal muscle for maintaining whole body glucose homeostasis. Studies in which GLUT4 has been ablated or 'knocked-out' provide proof that GLUT4 is the primary effector for mediating glucose transport in skeletal muscle and adipose tissue. Genetic ablation of GLUT4 results in impaired insulin tolerance and defects in glucose metabolism in skeletal muscle and adipose tissue. Because impaired muscle glucose transport leads to reduced whole body glucose uptake and hyperglycaemia, understanding the molecular regulation of glucose transport in skeletal muscle is important to develop effective strategies to prevent or reduce the incidence of Type II diabetes mellitus. In patients with Type II diabetes mellitus, reduced glucose transport in skeletal muscle is a major factor responsible for reduced whole body glucose uptake. Overexpression of GLUT4 in skeletal muscle improves glucose homeostasis in animal models of diabetes mellitus and protects against the development of diabetes mellitus. Thus, GLUT4 is an attractive target for pharmacological intervention strategies to control glucose homeostasis. This review will focus on the current understanding of the role of GLUT4 in regulating cellular glucose uptake and whole body glucose homeostasis.
Animals↗
Glucose and insulin responses in relation to insulin dose and caloric intake 12 h after acute physical exercise in men with IDDM.
Acute exercise in insulin-dependent diabetic patients may perturb glycemic control, and adjustments of insulin and diet might be required to avoid postexercise hypoglycemia. The aim of this study was to assess the role of alterations in insulin dose or caloric intake on blood glucose and free-insulin levels during 12 h after an evening bout of exercise. Nine insulin-dependent diabetic men (28-42 yr of age) receiving two daily injections with a combination of intermediate-acting and soluble insulin participated in the study. Patients were randomly assigned to four treatment protocols: A, 50% reduction in intermediate-acting insulin dose; B, 50% reduction in soluble insulin dose; C, extra caloric intake (1700 kJ) 1 h after exercise; and D, no change. Exercise consisted of 45 min of cycling at 60% of maximal oxygen uptake at each occasion. Glucose and insulin responses were similar for the four protocols. There was a significant (P less than .001) time effect found regardless of treatment, with lowest blood glucose values 75 min after exercise. Hypoglycemia occurred in six of the nine patients at some time during the study, with half of the occurrences on the control night (protocol D). Consistent individual plasma insulin and glucose patterns were observed independent of protocol used. In some patients, hypoglycemia was evident after reductions in insulin dose, and in others it was evident on the night increases in caloric intake were to occur; thus, none of the interventions were totally adequate in preventing exercise-induced hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Serum lipid and lipoprotein levels in female type I diabetics: relationships to aerobic capacity and glycaemic control.
The aims of this study were to examine the relationships between serum lipoprotein levels, glycaemic control and physical fitness in female Type I diabetic patients. Twenty-one patients were investigated. Those with the best glycemic control, as assessed by measurements of haemoglobin A1 levels, were found to have lower total triglyceride and VLDL triglyceride concentrations. They also had higher HDL and HDL2 cholesterol level than patients with less good control. Patients with high maximal oxygen uptake had higher HDL2 and lower LDL cholesterol levels as well as lower total triglyceride levels. It is concluded that both high aerobic capacity and good glycaemic control may be favourable for lipid status in Type I diabetic patients.
Adult↗