Insulin Prevention of Altered Muscarinic Receptor–G Protein Coupling in Diabetic Rat Atria

Abstract

Right atria from rats rendered diabetic by injection of streptozocin (STZ-D) for 8–10 wk are supersensitive to the negative chronotropic effects of muscarinic agonists but have decreased levels of muscarinic receptors and acetylcholinesterase activity. Insulin treatment completely prevents the development of these changes. The proportion of atrial muscarinic receptors displaying high-affinity agonist binding is lower in STZ-D rats; however, the sensitivity of high-affinity agonist binding to regulation by a guanine nucleotide (5′-guanylylimidodiphosphate) is greater in atria from diabetic rats. Again, insulin treatment eliminates these differences. These findings indicate that alterations in atrial muscarinic systems in STZ-D rats are a consequence of the elaboration of the diabetic state and suggest that an alteration of functional muscarinic receptor–G protein coupling contributes to the altered physiological responsiveness of the heart in diabetes.