Effects of Purinoceptor Agonists on Insulin Secretion

It is well known that adenosine triphosphate plays an important intracellular role in the insulin-secreting pancreatic B cell. For many years ATP was only considered as being an intracellular fuel; but more recently its key role in the regulation of insulin secretion through ATP-dependent K+ channels has been recognized and is now well documented. However, in addition to these intracellular effects, ATP is also able to act on the extracellular side of the B-cell membrane to increase insulin secretion. Furthermore, a nonphosphorylated adenine derivative, adenosine, can decrease this secretion. These two opposite effects are mediated through different types of purinoceptors for adenine nucleotides and nucleoside. In this paper we present a brief overview of the effects of ATP, adenosine, and structural analogues on insulin secretion. We discuss the pharmacologic characterization of B-cell purinoceptors, the proposed mechanisms involved, and the possible implication in physiologic and/or pathophysiologic states.