Introduction to the Diabetes Focus Issue ofEndocrinology
The current issue of Endocrinology emphasizes new advances in the study of diabetes mellitus. Physicians have been aware of both major forms of this disease since ancient times, but despite our efforts the number of people with diabetes is increasing around the world, reaching epidemic proportions in some populations. Type 1 diabetes results from autoimmune destruction of the ␤ cells in the Islets of Langerhans and tends to attack in youth. The pathophysiology of type 2 diabetes is more
... tes is more complex, involving impairments of insulin secretion, insulin action, and proper nutrient regulation in the liver. It is type 2's prevalence that is most alarmingly rising, especially among adolescents and younger adults, with most of that rise attributable to increases in obesity and concomitant lack of exercise. A better understanding of these diseases is occurring on several fronts, as evidenced by the broad spectrum of research on diabetes that is published in this journal. Relevant articles encompass topics as diverse as control of appetite and metabolism in the CNS, secretion and action of a number of hormones such as insulin and GLP-1, and hormonal control of metabolism. We have chosen to highlight three of these areas with invited "Perspective" articles written by well-known experts in the field. The insulin-producing ␤ cell is clearly the focus of the processes that result in type 1 diabetes, but the ␤ cell is also being increasingly recognized as being central if not predominantly causative of type 2 diabetes as well. In the case of type 1 diabetes, the harsh reality has been that once the ␤ cells are gone, the only practical option for therapy is insulin replacement with its attendant imperfect glycemic control, resulting in debilitating vascular complications and/or hypoglycemia. However, a better understanding is emerging of the processes that result in ␤ cell death and of the rules that determine ␤ cell growth and differentiation. These insights may open new doors for treatment that could lead to rescue and repopulation of ␤ cells. In her perspective, Susan Bonner-Weir addresses these fields of ␤ cell apoptosis and regeneration. Even with intact insulin secretion, one of the central problems in type 2 diabetes is resistance to normal hormone action. Morris White, in his review, deals with the early steps in signal transduction that culminate in insulin exerting its pleiotropic metabolic effects, with a focus on the role of the IRS proteins. Work from his and other laboratories has demonstrated their central role in normal insulin action, not only in the classical target tissues of insulin-liver, muscle, and fat-but the ␤ cell as well. This work suggests a possible unifying hypothesis for the failure of both hormone secretion and hormone action that is seen in type 2 diabetes. Finally, Luciano Rossetti comments on the hexosamine pathway of glucose metabolism as an integrative satiety sensor for cells and tissues. The fact that when we eat too much we get fat should surprise no one, but exactly how the body coordinates the disposition of excess calories to fat tissue is less well understood. Furthermore, how obesity and caloric excess lead to the phenotypic characteristics of diabetesinsulin resistance, ␤ cell failure, and excessive hepatic glucose production-is still a mystery. Dr. Rossetti reviews work suggesting that the hexosamine pathway is used by cells to sense excess carbohydrate and fatty acid flux. This leads to a host of responses including insulin resistance in muscle, production of leptin, and alterations in hepatic glucose handling that are adaptive in the short run but contribute to diabetes when the organism is chronically overfed. Results in all of these areas are exciting and putting us ever nearer to understanding and curing diabetes. Endocrinology plans to be able to continue to play a role in that quest through the publication of the most important new experimental research findings in this field.