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Horm Metab Res 1976; 8(3): 184-190
DOI: 10.1055/s-0028-1093657
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© Georg Thieme Verlag KG Stuttgart · New York

Effects of Insulin and Procaine Hydrochloride on Glycogen Synthetase Activation and Adipocyte Calcium Flux: Evidence for a Role of Calcium in Insulin Activation of Glycogen Synthetase

H. F. Hope-Gill , A. H. Kissebah , P.  Clarke , N.  Vydelingum , B.  Tulloch , T. R. Fraser
  • Endocrine Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, England and Department of Medicine, Sunnybrook Hospital, University of Toronto Medical School, Toronto, Canada
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Publication Date:
23 December 2008 (online)

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Abstract

Observations that insulin-induced stimulation of glycogen synthetase occurs without detectable reduction in cyclic AMP suggests an alternative controlling mechanism. The hypothesis that this stimulation might be mediated through calcium was tested using procaine HCl, a drug whose insulin-like action is not associated with reduction in basal or adrenaline-stimulated cyclic AMP levels.

Pretreatment of adipose tissue with insulin or procaine for 30 minutes increased homogenate glucose-6-phosphate independent ("I") form activity by 58% and 48% respectively with no significant change in total activity.

Insulin and procaine also had similar effects on calcium efflux from isolated rat adipocytes. Following an initial displacement of calcium from the adipocytes by insulin (but not by procaine) both agents decreased efflux of calcium, measured following 10, 20 and 30 minutes incubation.

In adipose tissue homogenates increasing the free calcium concentration from 10-8 to 10-3M increased "I" form glycogen synthetase activity without significantly altering total activity. A complex interrelationship with ATP and calcium was also observed. In the presence of ATP 0.5 mM maximal activation occurred at 10-6M calcium whereas ATP inhibited "I" form activity at 10-3M free calcium concentration.

These findings suggest that insulin-induced activation of glycogen synthetase may be effected by alteration of intracellular free calcium with consequent effects on glycogen synthetase-related enzymes in a mechanism independent of or complementary to effects on cyclic AMP levels.

Key words

Adipose Tissue - ATP - Calcium - Cyclic AMP - Glycogen - Glycogen Synthetase - Glycogen Synthetase Phosphatase - Procaine HCl - Protein Kinase

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