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Research Article Free access | 10.1172/JCI109609

Effect of Fasting and Streptozotocin Diabetes on Insulin Binding and Action in the Isolated Mouse Soleus Muscle

Y. Le Marchand-Brustel and P. Freychet

Institut National de la Santé et de la Recherche Médicale, Groupe de Recherches sur les Hormones Polypeptidiques et la Physiopathologie Endocrinienne, U 145, France

Laboratoire de Médecine Expérimentale, Faculté de Médecine, Université de Nice, Chemin de Vallombrose, 06034 Nice Cedex, France

Find articles by Le Marchand-Brustel, Y. in: PubMed | Google Scholar

Institut National de la Santé et de la Recherche Médicale, Groupe de Recherches sur les Hormones Polypeptidiques et la Physiopathologie Endocrinienne, U 145, France

Laboratoire de Médecine Expérimentale, Faculté de Médecine, Université de Nice, Chemin de Vallombrose, 06034 Nice Cedex, France

Find articles by Freychet, P. in: PubMed | Google Scholar

Published November 1, 1979 - More info

Published in Volume 64, Issue 5 on November 1, 1979
J Clin Invest. 1979;64(5):1505–1515. https://doi.org/10.1172/JCI109609.
© 1979 The American Society for Clinical Investigation
Published November 1, 1979 - Version history
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Abstract

To investigate whether skeletal muscle is resistant to insulin in insulinopenic states, insulin binding and biological effects on glucose utilization were studied in isolated soleus muscles from 24- or 48-h-fasted mice and from streptozotocin-diabetic mice. Both 48-h fasting and diabetes led to an increase in insulin binding at insulin concentrations <3.4 nM. In both states, submaximal concentrations of insulin were also more effective in stimulating muscle 2-deoxyglucose uptake and glycogen synthesis, and in activating glycogen synthase. This resulted in a two- to fourfold leftward shift in the insulin dose-response curves in muscles from both groups compared with control. No change in insulin binding or biological effects was detected in muscles from 24-h-fasted mice. Maximal insulin effectiveness on 2-deoxyglucose uptake and glycolysis was either unchanged or only slightly enhanced in 48-h-fasted mice and in diabetic animals, compared with controls. Maximal insulin effects on glycogen synthesis and glycogen synthase activation were unaltered by fasting or diabetes. Basal glucose uptake and glycolysis were similar in all groups of mice. In conclusion, when soleus muscles from 48-h-fasted mice and from diabetic mice are compared with controls it can be observed that, (a) at low insulin concentrations insulin binding is increased and insulin effectiveness in stimulating glucose transport and metabolism is enhanced; (b) biological responses to maximally effective insulin concentrations are either unaltered or slightly increased; (c) basal rates of glucose transport and metabolism are essentially unaltered. These results indicate that in insulinopenic states soleus muscle is not insulin resistant in vitro but is hypersensitive to low concentrations of insulin, and normally responsive to maximally effective doses of the hormone.

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