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Genetic models of Insulin Resistance:Alterations in β-cell biology

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Molecular Basis of Pancreas Development and Function

Part of the book series: Endocrine Updates ((ENDO,volume 11))

Abstract

One of the essential biological actions of insulin in mammals is the maintenance of euglycaemia. This is a complex process and involves the uptake, storage and oxidation of glucose in skeletal muscle and adipose tissues, as well as the suppression of hepatic glucose production. A significant blunting of these actions in spite of the presence of normal or even high circulating levels of insulin indicates the presence of an “insulin resistant” phenotype. A variety of pathological states including type 2 diabetes, obesity, hypertension, atherosclerosis and polycystic ovary disease are characterized by the presence of insulin resistance (1-6). In the case of type 2 diabetes it is generally accepted that insulin resistance must be accompanied by a β-cell defect for the full development of the disease. Although there is some debate as to which of these two defects is primary, longitudinal studies in several populations suggest that insulin resistance may be the first defect to be detected (2,7,8). The early insulin resistance observed in pre-diabetic individuals is initially compensated by an increase in insulin secretion by the islet β-cells that could represent either an enhanced secretory capacity or an increased islet/β-cell mass or a combination of both. Over a period of time, however, the β-cell compensation fails leading to uncontrolled hyperglycaemia and overt diabetes.

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Authors and Affiliations

  1. Joslin Diabetes Center and Department of Medicine, Harvard Medical School, One Joslin Place, Boston, MA, 02215, USA

    Rohit N. Kulkarni M.D., Ph.D. & C. Ronald Kahn M.D.

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  1. Rohit N. Kulkarni M.D., Ph.D.
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  2. C. Ronald Kahn M.D.
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Editors and Affiliations

  1. Laboratory of Molecular Endocrinology, Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA

    Joel F. Habener M.D.

  2. Department of Medicine, Clinical and Molecular Endocrinology, New York University Medical Center, New York, NY

    Mehboob A. Hussain M.D.

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© 2001 Springer Science+Business Media New York

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Kulkarni, R.N., Kahn, C.R. (2001). Genetic models of Insulin Resistance:Alterations in β-cell biology. In: Habener, J.F., Hussain, M.A. (eds) Molecular Basis of Pancreas Development and Function. Endocrine Updates, vol 11. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1669-9_18

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  • DOI: https://doi.org/10.1007/978-1-4615-1669-9_18

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