Glucose transport into skeletal muscle. Influence of contractile activity, insulin, catecholamines and diabetes mellitus.
The influence of contractile activity, insulin, catecholamines and diabetes mellitus on the acute as well as long-term regulation of glucose transport into skeletal muscle was investigated. In Paper I, glucose uptake was determined in the perfused hindlimb preparation; in Papers II-VI the glucose transport process was studied independently of glucose metabolism by determining the uptake of the non-metabolizable glucose analogue 3-O-methylglucose into isolated rat epitrochlearis muscles. The main findings are: Acute regulation of muscle glucose transport: 1. Muscle contraction-induced glucose uptake does not require the presence of insulin. 2. Exercise and a maximal insulin stimulus have additive effects on glucose transport. 3. Catecholamines decrease non-insulin-mediated glucose transport in the absence of albumin, whereas in the presence of albumin an enhancement occurs. 4. The effects of catecholamines are abolished during beta-adrenergic blockade, but remain unaffected during alpha-adrenergic blockade. Long-term regulation of muscle glucose transport: 5. The rat epitrochlearis muscle, a thin, predominantly fast-twitch muscle of the forearm, was shown to be a suitable preparation for the study of factors regulating glucose transport capacity on a long-term basis, since it maintains energy stores and tissue oxygenation for periods of at least 14 h. 6. Sustained insulin deficiency results in marked decreases in basal (40-45%), contraction-induced (50-60%), and insulin-stimulated (65-70%) glucose transport into rat epitrochlearis muscle. 7. The decreased contraction-induced glucose transport capacity can be prevented by frequent exercise during the period of insulin deficiency. 8. The decreased insulin responsiveness of the muscle glucose transport system can be reversed either by treating previously untreated diabetic rats with insulin or by in vitro incubation of the muscles for 12-14 hours. 9. The in vitro normalization of the insulin-stimulated glucose transport capacity (a) does not require the presence of serum or insulin, (b) occurs despite high (30 mM) concentrations of glucose, (c) is incomplete in the presence of diabetic serum and (d) is blocked to the amount of 30-80% in the presence of protein synthesis inhibition. On the basis of these findings, the following is concluded: Muscle contraction can activate the glucose transport system independently of insulin.(ABSTRACT TRUNCATED AT 400 WORDS)
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004837:Epinephrine / Q000502:physiology*; D005947:Glucose / Q000493:pharmacokinetics*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood; D007333:Insulin Resistance; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000378:metabolism*; D009638:Norepinephrine / Q000502:physiology*; D005082:Physical Exertion; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D007328:Insulin; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine