title: The effects of insulin on transport and metabolism of glucose in skeletal muscle from hyperthyroid and hypothyroid rats.
abstract: The effects of insulin on the rates of glucose disposal were studied in soleus muscles isolated from hyper- or hypothyroid rats. Treatment with triiodothyronine for 5 or 10 days decreased the sensitivity of glycogen synthesis but increased the sensitivity of lactate formation to insulin. The sensitivity of 3-O methylglucose to insulin was increased only after 10 days of treatment and was accompanied by an increase in the sensitivity of 2-deoxyglucose phosphorylation; however, 2-deoxyglucose and glucose 6-phosphate in response to insulin remained unaltered. In hypothyroidism, insulin-stimulated rates of 3-O-methylglucose transport and 2-deoxyglucose phosphorylation were decreased; however, at basal levels of insulin, 3-O-methylglucose transport was increased, while 2-deoxyglucose phosphorylation was normal. In these muscles, the sensitivity of lactate formation to insulin was decreased; this defect was improved after incubation of the muscles with prostaglandin E2. The results suggest: (a) in hyperthyroidism, insulin-stimulated rates of glucose utilization in muscle to form lactate are increased mainly because of a decrease in glycogen synthesis; when hyperthyroidism progresses in severity, increases in the sensitivity of glucose transport to insulin and in the activity of hexokinase may also be involved; (b) in hypothyroidism, the decrease in insulin-stimulated rates of glucose utilization is caused by decreased rates of glycolysis; (c) prostaglandins may be involved in the changes in sensitivity of glucose utilization to insulin observed in muscle in altered thyroid states.
authors.affiliation: Department of Biochemistry, University of Oxford, UK.
authors.forename: G
authors.initials: G
authors.lastname: Dimitriadis
authors.forename: M
authors.initials: M
authors.lastname: Parry-Billings
authors.forename: S
authors.initials: S
authors.lastname: Bevan
authors.forename: B
authors.initials: B
authors.lastname: Leighton
authors.forename: U
authors.initials: U
authors.lastname: Krause
authors.forename: T
authors.initials: T
authors.lastname: Piva
authors.forename: K
authors.initials: K
authors.lastname: Tegos
authors.forename: R A
authors.initials: RA
authors.lastname: Challiss
authors.forename: G
authors.initials: G
authors.lastname: Wegener
authors.forename: E A
authors.initials: EA
authors.lastname: Newsholme
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003348:Cortisone / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004347:Drug Interactions; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D006019:Glycolysis; D013006:Growth Hormone / Q000494:pharmacology; D006980:Hyperthyroidism / Q000139:chemically induced / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D019344:Lactic Acid / Q000096:biosynthesis; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D007328:Insulin; D014284:Triiodothyronine; D019344:Lactic Acid; D013006:Growth Hormone; D006003:Glycogen; D005947:Glucose; D015232:Dinoprostone; D003348:Cortisone