Serial changes in the myocardial beta-adrenergic signalling system in two models of non-insulin dependent diabetes mellitus.

Since it was reported in 1991 by Schaffer et al. that myocardial contractile responsiveness was altered in NIDDM in the absence of alterations in the beta-adrenergic receptor population, researchers have been seeking a post-receptor defect to account for this. The present study addresses this issue by comparing alterations occurring in the myocardial beta-receptor signalling pathway in two different models of rat NIDDM, as well as the response of the pathway after stimulation with isoproterenol in the presence or absence of insulin. The characteristics of the beta-receptor population, adenylyl cyclase activity and cAMP levels were determined at three different ages. The main results demonstrate that: (i) the two models of NIDDM myocardium differ biochemically; (ii) the beta-adrenergic signalling system of the insulin deficient model was altered more than the hyperinsulinemic model and (iii) the observed exaggerated cAMP response of NIDDM hearts after stimulation with a beta-adrenergic agonist is in contrast with lower responsivity.