Effect of Manganese Deficiency on Glucose Transport and Insulin Binding in Rat Adipocytes

Abstract

Manganese deficiency results in altered carbohydrate metabolism; both at the level of pancreatic insulin biosynthesis (1) and gluconeogenesis (2). The effects of manganese deficiency on peripheral actions of insulin, however, have not been examined. Evidence of a role for manganese in mediating peripheral actions of insulin has come from several studies. It is well recognized that the insulin receptor is a hormone-dependent kinase that is stimulated by both Mg2+ and Mn2+ (3). Ueda and coworkers (4) have also demonstrated that Mn2+ mildly enhances the extracellular binding of insulin to its receptor, facilitates the physiological actions of insulin and mimics the action of the hormone. Although the role of insulin receptor phosphorylation in the mechanism of insulin action is still disputed, the authors postulate that the insulinomimetic action of Mn2+ may be related to its ability to cause the phosphorylation of the s-subunit of the insulin reeptor and thus “turn on” insulin-related events. Alternatively, Mn2+ may be acting at some step distal to the insulin receptor, such as adenylate cyclase linked processes. In the present studies, we have begun to examine the effect of Mn deficiency on these processes.