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 contractil e 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 signal ling pathway in two different models of rat NIDDM, as well as the response of the pathway after stimulation with isoproterenol in the presence or abse nce of insulin. The characteristics of the beta -receptor population, adeny lyl cyclase activity and cAMP levels were determined at three different age s. The main results demonstrate that: (i) the two models of NIDDM myocardiu m differ biochemically; (ii) the beta -adrenergic signalling system of the insulin deficient model was altered more than the hyperinsulinemic model an d (iii) the observed exaggerated cAMP response of NIDDM hearts after stimul ation with a beta -adrenergic agonist is in contrast with lower responsivit y.