A role for the endocrine and pro-inflammatory mediator MIF in the control of insulin secretion during stress

The systemic response to injury or infection is often accompanied by signif icant alterations in host metabolism and glucose homeostasis. Within the li ver, these changes include a decrease in glycogenesis and an increase in gl uconeogenesis, and in peripheral tissues, the development of insulin resist ance and the increased utilization of glucose by non-insulin-dependent path ways. Depending on the severity and the duration of the response, both hype r- and hypoglycemia can ensue and each can become a clinically important ma nifestation of the systemic inflammatory response. The protein known as mac rophage migration inhibitory factor (MIF) has been identified recently to p lay a central role in host immunity and to regulate glucocorticoid effects on the immune and inflammatory systems. MIF is released in vivo from activa ted immune cells as well as by the anterior pituitary gland upon stimulatio n of the hypothalamic-pituitary-adrenal axis. MIF also has been found to be secreted together with insulin from the pancreatic beta-cells and to act a s an autocrine factor to stimulate insulin release. Since circulating MIF l evels are elevated during stress or systemic inflammatory processes, this p rotein may play a central role in the control of insulin secretion during v arious disease states. Copyright (C) 1999 John Wiley & Sons, Ltd.