Molecular Defects in Diabetes Mellitus

  1. Graeme I Bell
  1. Howard Hughes Medical Institute and Departments of Biochemistry and Molecular Biology and of Medicine, The University of Chicago Chicago, Illinois
  1. Address correspondence and reprint requests to Graeme I. Bell, Howard Hughes Medical Institute, The University of Chicago, 5841 South Maryland Avenue, Box 391, Chicago, IL 60637.

Abstract

The application of molecular biology to problems in diabetes mellitus has begun to reveal the underlying molecular defects contributing to the development of hyperglycemia. Islet amyloid represents the most common pathological lesion occurring in the islets of NIDDM subjects. The use of both biochemistry and molecular biology has lead to the identification of the major protein component of human islet amyloid and elucidation of the structure of its precursor. This protein, termed islet amyloid polypeptide, is related to two neuropeptides, calcitonin gene–related peptides 1 and 2, and represents a new β-cell secretory product whose normal physiological function remains to be determined. The use of molecular biology has also led to a better understanding of the molecular defects contributing to insulin resistance. Characterization of the insulin-receptor gene in patients with extreme forms of insulin resistance has resulted in the identification of mutations that impair its function and lead to tissue resistance to the action of insulin. Molecular biological approaches have also led to a better understanding of the regulation of glucose transport. They have revealed that there is a family of structurally related proteins encoded by distinct genes and expressed in a tissue-specific manner that are responsible for the transport of glucose across the plasma membrane. Moreover, they have shown that specific depletion of the glucose-transporter isoform that mediates insulin-stimulated glucose transport is responsible for decreased transport activity in adipose tissue in insulin-resistant states.

  • Received November 15, 1990.
  • Revision received November 30, 1990.
  • Accepted November 30, 1990.
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