AJP - Endocrinology and Metabolism, Vol 246, Issue 2 134-E140, Copyright © 1984 by American Physiological Society
Phosphorylase activation hypersensitivity in hearts of diabetic rats
T. B. Miller Jr
A hypersensitivity of glycogen phosphorylase activation by epinephrine and
glucagon has been demonstrated in isolated perfused working and non-working
hearts from diabetic rats. Accumulation of tissue cAMP and activation of
cAMP-dependent protein kinase in response to epinephrine and glucagon were
no greater and usually less in hearts of diabetic than of normal rats.
Insulin deficiency was not associated with greater changes in
epinephrine-induced activation of glycogen phosphorylase kinase than that
observed in normal hearts. Perfusion of hearts with subphysiological
concentrations of calcium (0.83 mM) partially reversed the diabetes-related
hypersensitivity of phosphorylase activation by epinephrine. The
phosphorylase activation hypersensitivity to epinephrine was completely
reversed by adrenalectomizing diabetic rats 5 days before heart perfusion,
an effect potentially caused by steroid-induced changes in cardiac calcium
metabolism. These data are consistent with the hypothesis that
phosphorylase activation by phosphorylase kinase is allosterically
increased in the diabetic due to a diabetes-related increase in free
intracellular calcium concentrations.
