Insulin Gene Mutations and Abnormal Products of the Human Insulin Gene

In many ways, the study of insulin, the pancreatic B cell, and diabetes has provided a paradigm for the analysis of various aspects of endocrine function, ranging from clinical diagnosis and management to biochemistry and cell and molecular biology. Diabetes is, of course, a complex disease with both multiple causes and multiple consequences. Although the terms juvenile onset and maturity onset, type I and type II, and most recently insulin-dependent and non-insulin-dependent have been applied to the disease, none of these terms are completely satisfactory, and none specifically address the cause of glucose intolerance. In this regard, one must deal at least with matters such as the potential loss of (a) B cell mass (arising most probably from autoimmune B cell death in insulin-dependent diabetes), (b) B cell secretetory responses to glucose and other secretogogues (notwithstanding adequate B cell numbers and associated insulin stores), and (c) peripheral insulin sensitivity (due to receptor or postreceptor defects at insulin target cells).