PURINERGIC RECEPTORS AND METABOLIC FUNCTION

Blood glucose concentration is a signal for the endocrine pancreas to release insulin or glucagon. Insulin lowers the level of glucose by in hibiting the hepatic glucose production and stimulating glucose utiliz ation by skeletal muscles and adipocytes. In these latter cells, insul in also inhibits lipolysis and the subsequent release of glycerol (a g luconeogenic precursor) and non esterified fatty acids (energy substra te for hepatic gluconeogenesis). Glucagon opposes the effects of insul in, particularly in the liver, where it stimulates glycogenolysis and neoglucogenesis. A variety of purinoceptor subtypes are expressed in t hese different tissues, all involved in the regulation of glucose home ostasis: 1) P2Y and A(1) receptors in the pancreatic B cell, mediating stimulation or inhibition of insulin secretion respectively, A(2) rec eptors in the pancreatic A cell mediating glucagon secretion; 2) diffe rent P2 receptors in liver cells mediating glycogenolysis through mult iple transducing systems; 3) A(1) receptors in adipocytes mediating an tilipolytic action. The thorough characterization of these receptors, together with a better understanding of their metabolic role and posit ion in this integrated physiological regulation may be useful in desig ning ligands aimed at stimulating insulin secretion or reducing insuli n resistance, which are both critical in the pathophysiology of non-in sulin-dependent diabetes mellitus (NIDDM). Thus, purinoceptors may con stitute new targets for pharmacological compounds with potential thera peutic applications in NIDDM, such as P2Y agonists as insulin secretag ogues and A(1) agonists as antilipolytic agents for improvement of ins ulin sensitivity. (C) 1997 Wiley-Liss, Inc.