Liver and muscle insulin sensitivity, glycogen concentration and glycogen synthase activity in a rat model of non-insulin-dependent diabetes.
Mild diabetes was induced in adult rats with streptozotocin (45 mg/kg body weight), and insulin sensitivity, glycogen deposition and glycogen synthase activity assessed in liver and muscle 5 weeks later. Diabetic rats had significantly elevated fasting blood glucose concentrations (5.6 +/- 0.1 versus 3.6 +/- 0.1 mmol/l, p less than 0.001), and blood glucose concentrations 2 h after a 1 g/kg glucose load (12.0 +/- 0.6 versus 3.7 +/- 0.2 mmol/l, p less than 0.001). After a 20-h fast hepatic glucose output was significantly elevated (58 +/- 3 versus 47 +/- 3 mumol.min-1.kg-1, p less than 0.05), and failed to suppress at high insulin concentrations during a euglycaemic clamp (hepatic glucose output 21 +/- 4 versus 2 +/- 4 mumol.min-1.kg-1, p less than 0.02). Liver glycogen was lower in the diabetic rats by the end of the clamp (16 +/- 3 versus 38 +/- 6 mumol/g wet wt, p less than 0.05). At the end of the clamp total glucose turnover was lower in the diabetic rats (107 +/- 4 versus 161 +/- 17 mumol.min-1.kg-1, p less than 0.01), as was skeletal muscle glycogen synthase activity (0.46 +/- 0.04 versus 0.67 +/- 0.05 U/g wet wt, p less than 0.01) and glycogen concentration (22 +/- 2 versus 33 +/- 3 mumol/g wet wt, p less than 0.05). Blood lactate and pyruvate responses suggested that glycolytic pathways were similarly affected. Thus, insulin insensitivity develops in both liver and skeletal muscle after 5 weeks of mild streptozotocin-induced diabetes.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005215:Fasting; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D008112:Liver Glycogen; D006003:Glycogen; D006006:Glycogen Synthase