Relationship of skeletal muscle glucose 6-phosphate to glucose disposal rate and glycogen synthase activity in insulin-resistant and non-insulin-dependent diabetic rhesus monkeys.
Reduced insulin action on skeletal muscle glycogen synthase activity and reduced whole-body insulin-mediated glucose disposal rates in insulin-resistant subjects may be associated with an alteration in muscle glucose transport (or phosphorylation) or with a defect distal to glucose 6-phosphate. To examine this issue we determined the glucose 6-phosphate concentration and glycogen synthase activity in muscle samples obtained under basal and euglycaemic hyperinsulinaemic clamp conditions in 27 rhesus monkeys (Macaca mulatta). They ranged from metabolically normal (n = 11) to insulin-resistant (n = 8) to overtly diabetic (non-insulin-dependent) (n = 8). The glucose 6-phosphate measured under insulin-stimulated conditions was inversely correlated to insulin-stimulated glycogen synthase independent activity (r = -0.54, p < 0.005), the change in glycogen synthase independent activity (insulin-stimulated minus basal) (r = -0.58, p < 0.002) and to whole-body insulin-mediated glucose disposal rate (r = -0.60, p < 0.002). The insulin-resistant and diabetic monkeys had significantly higher insulin-stimulated glucose 6-phosphate concentrations (0.57 +/- 0.11 and 0.62 +/- 0.11 nmol/mg dry weight, respectively) compared to the normal monkeys (0.29 +/- 0.05 nmol/mg dry weight) (p's < 0.05). We conclude that under euglycaemic/hyperinsulinaemic conditions, a defect distal to glucose 6-phosphate is a major contributor to reduced whole-body insulin-mediated glucose disposal rates and to reduced insulin action on glycogen synthase in insulin-resistant and diabetic monkeys.
Ortmeyer
H K
HK
Department of Physiology, School of Medicine, University of Maryland at Baltimore 21201.
Bodkin
N L
NL
Hansen
B C
BC
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000662:veterinary*; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D006019:Glycolysis; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D008253:Macaca mulatta; D008992:Monkey Diseases; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values
D001786:Blood Glucose; D005958:Glucosephosphates; D007328:Insulin; D019298:Glucose-6-Phosphate; D006006:Glycogen Synthase; D005947:Glucose