The Molecular Basis of Insulin Action and Insulin Resistance

  • Joseph Avruch
Part of the Endocrine Updates book series (ENDO, volume 10)


Type 2 diabetes (previously called non-insulin dependent diabetes, NIDDM) is a common, phenotypically heterogeneous syndrome that has a strong genetic basis, most clearly indicated by the roughly 70% concordance in identical sibs, a concordance at least twice as high as in nonidentical sibs, and also considerably higher than the 30-40% concordance observed in identical twins sets, wherein one sib has autoimmune Type 1 diabetes (1). Despite this convincing evidence for heritability, it is clear that environmental factors greatly affect the penetrance of the Type 2 diabetic phenotype. In particular, dietary composition, overall calorie excess leading to weight gain in adult life, and low physical activity each strongly promote the expression of Type 2 diabetes (2). Moreover, epidemiologic evidence points to strong correlations between several aspects of the intrauterine environment and prenatal nutritional experience and the occurrence of Type 2 diabetes as an adult. This has been well described in the Native American population known as the Pima Indians of Arizona; in comparing the offspring of Type 2 diabetic mothers, the presence of hyperglycemia in utero is associated with a much higher prevalence of diabetes in adult life than occurs if the mother became hyperglycemic only after the pregnancy. Infants of hyperglycemic diabetic mothers are hyperinsulinemic in utero and large at birth, reflecting the strong positive influence of insulin on fetal growth. Conversely, evidence both in the Pima and several other populations (UK, Hispanic-American) indicates that low birth weight (<2500gms) and low weight at one year also correlate positively with the emergence in adult life of a syndrome of insulin resistance, hypertension and excess atherosclerotic vascular disease (2, 3, 4, 5, 6, 7).


Insulin Resistance Insulin Receptor Insulin Action Insulin Receptor Substrate GLUT4 Translocation 
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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Joseph Avruch
    • 1
  1. 1.Massachusetts General HospitalHarvard Medical SchoolBoston

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