title: Hyperglycaemia compensates for the defects in insulin-mediated glucose metabolism and in the activation of glycogen synthase in the skeletal muscle of patients with type 2 (non-insulin-dependent) diabetes mellitus.
abstract: Insulin resistance and a defective insulin activation of the enzyme glycogen synthase in skeletal muscle during euglycaemia may have important pathophysiological implications in Type 2 (non-insulin-dependent) diabetes mellitus. Hyperglycaemia may serve to compensate for these defects in Type 2 diabetes by increasing glucose disposal through a mass action effect. In the present study, rates of whole-body glucose oxidation and glucose storage were measured during fasting hyperglycaemia and isoglycaemic insulin infusion (40 mU.m-2.min-1, 3 h) in 12 patients with Type 2 diabetes. Eleven control subjects were studied during euglycaemia. Biopsies were taken from the vastus lateralis muscle. Fasting and insulin-stimulated glucose oxidation, glucose storage and muscle glycogen synthase activation were all fully compensated (normalized) during hyperglycaemia in the diabetic patients. The insulin-stimulated increase in muscle glycogen content was the same in the diabetic patients and in the control subjects. Besides hyperglycaemia, the diabetic patients had elevated muscle free glucose and glucose 6-phosphate concentrations. A positive correlation was demonstrated between intracellular free glucose concentration and muscle glycogen synthase fractional velocity insulin activation (0.1 mmol/l glucose 6-phosphate: r = 0.65, p less than 0.02 and 0.0 mmol/l glucose 6-phosphate: r = 0.91, p less than 0.0001). In conclusion, this study indicates an important role for hyperglycaemia and elevated muscle free glucose and glucose 6-phosphate concentrations in compensating (normalizing) intracellular glucose metabolism and skeletal muscle glycogen synthase activation in Type 2 diabetes.
authors.affiliation: Department of Endocrinology and Internal Medicine M, Odense University Hospital, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Vaag
authors.forename: P
authors.initials: P
authors.lastname: Damsbo
authors.forename: O
authors.initials: O
authors.lastname: Hother-Nielsen
authors.forename: H
authors.initials: H
authors.lastname: Beck-Nielsen
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002151:Calorimetry; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D004789:Enzyme Activation; D005215:Fasting; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism*; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005947:Glucose; D006442:Glycated Hemoglobin; D006003:Glycogen; D006006:Glycogen Synthase; D007328:Insulin