Insulin action and insulin resistance: diseases involving defects in insulin receptors, signal transduction, and the glucose transport effector system 1

  • Steven J Hunter
    Requests for reprints should be addressed to W. Timothy Garvey, MD, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425
    Department of Medicine, Medical University of South Carolina, and the Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, USA
    Search for articles by this author
  • W.Timothy Garvey
    Department of Medicine, Medical University of South Carolina, and the Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, USA
    Search for articles by this author
      The concept of insulin resistance arose with the availability of insulin therapy for diabetes mellitus. It soon became evident that diabetic patients could be divided into two groups based on their relative sensitivity to the glucose-lowering effects of exogenous insulin, corresponding broadly to the modern classification of Type 1 and Type 2 diabetes (
      • Himsworth H.P
      Diabetes mellitus. Its differentiation into insulin-sensitive and insulin-insensitive types.
      ). Later the term was applied to patients requiring large doses of insulin (>200 units/day) in association with circulating antibodies induced by partially purified bovine and porcine insulin preparations (
      • Shipp J.C
      • Cunningham R.W
      • Russell R.D
      • Marble A
      Insulin resistance. Clinical features, natural course and effects of adrenal steroid treatment.
      ). The insulin radioimmunoassay, developed in 1960 (
      • Yalow R.S
      • Berson S.A
      Plasma insulin concentrations in nondiabetic and early diabetic subjects. Determinations by a new sensitive immunoassay technique.
      ), definitively distinguished Type 1 diabetic patients with absolute insulin deficiency from Type 2 diabetic patients who were found to have normal or elevated fasting serum insulin levels. Many normoglycemic individuals were also found to be hyperinsulinemic. Hyperinsulinemia in conjunction with normoglycemia or hyperglycemia was soon recognized as the cardinal manifestation of insulin resistance, together with its modern definition as a condition in which a normal amount of insulin produces a subnormal biological response (
      • Kahn C.R
      Insulin resistance, insulin sensitivity and insulin unresponsiveness. A necessary distinction.
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