Amylin activates glycogen phosphorylase and inactivates glycogen synthase via a cAMP-independent mechanism.
Although the novel pancreatic peptide amylin has been shown to induce insulin resistance and decrease glucose uptake, the mechanism of amylin's actions is unknown. The following study evaluated the effect of amylin on glycogen metabolism in isolated soleus muscles in the presence and absence of insulin (200 microU/ml). Total glycogen, glycogen phosphorylase and glycogen synthases activities, and cAMP levels were measured. Total glycogen levels were significantly decreased by amylin (100 nM) in fed or fasted muscles under conditions of insulin stimulation. Amylin (100 nM) activated glycogen phosphorylase by as much as 100% and decreased glycogen synthase activity by over 60%, depending on the metabolic state of the muscles. These effects where comparable to those of the beta adrenergic agonist isoproterenol. A lower concentration of amylin (1 nM) did not significantly affect glycogen levels, glycogen phosphorylase, or glycogen synthase activity. Cyclic AMP levels were increased two-fold by isoproterenol but were unaffected by amylin. In conclusion, amylin induces glycogenolysis by decreasing glycogen synthesis and increasing breakdown. The effect of amylin on enzyme activity is consistent with a phosphorylation-dependent mechanism. It is likely that these events are mediated via a cAMP independent protein kinase.
Deems
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RO
Sandoz Research Institute, East Hanover, NJ 07936.
Deacon
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Young
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DA
D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D004789:Enzyme Activation; D005215:Fasting; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D058228:Islet Amyloid Polypeptide; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000201:enzymology*; D006005:Phosphorylases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D006003:Glycogen; D000242:Cyclic AMP; D006005:Phosphorylases; D006006:Glycogen Synthase; D007545:Isoproterenol