Insulin resistance/Bibliography

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Journal articles

• Melnik BC. (2009) Permanent impairment of insulin resistance from pregnancy to adulthood: the primary basic risk factor of chronic Western diseases. Med Hypotheses 73:670-81.
  • Excerpt: It is the intention of this hypothesis paper to provide evidence that IR and increased insulin/IGF-1 signalling is important for all life phases with physiologic growth requirements and is the major effector of all risk factors of chronic Western diseases...It will be shown that Western life style risk factors like obesity, consumption of cow milk and dairy products, hyperalimentation, increased intake of food with high glycaemic index, use of hormonal contraceptives, androgen abuse, common drugs like beta-adrenergic blockers and glucocorticoids, smoking, and inadequate physical exercise altogether permanently induce pathologic IR [insulin resistance] beginning already during pregnancy and fetal life persisting into adulthood. IR causes hyperinsulinaemia and elevated serum levels of IGF-1 [insulin-like growth factor 1]. Both hormones are potent mitogens, stimulate growth, cell proliferation, and exert anti-apoptotic activity, which have been correlated with the pathophysiology of metabolic disorders, cardiovascular diseases, cancer and neurodegenerative disorders…This hypothesis shows for the first time that all chronic Western diseases may be related to a common underlying pathogenic key mechanism of well known risk factors of chronic Western diseases, i.e., insulin resistance. In order to assess an individual’s personal risk constellation, all risk factors associated with IR have to be taken into account.

• Graham TE, Yang Q, Bluher M et al. (2006) Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med 354:2552-63.
  • Insulin resistance has a causal role in type 2 diabetes. Serum levels of retinol-binding protein 4 (RBP4), a protein secreted by adipocytes, are increased in insulin-resistant states. Experiments in mice suggest that elevated RBP4 levels cause insulin resistance…We measured serum RBP4, insulin resistance, and components of the metabolic syndrome in three groups of subjects. Measurements were repeated after exercise training in one group. GLUT4 protein was measured in isolated adipocytes…Serum RBP4 levels correlated with the magnitude of insulin resistance in subjects with obesity, impaired glucose tolerance, or type 2 diabetes and in nonobese, nondiabetic subjects with a strong family history of type 2 diabetes. Elevated serum RBP4 was associated with components of the metabolic syndrome, including increased body-mass index, waist-to-hip ratio, serum triglyceride levels, and systolic blood pressure and decreased high-density lipoprotein cholesterol levels. Exercise training was associated with a reduction in serum RBP4 levels only in subjects in whom insulin resistance improved. Adipocyte GLUT4 protein and serum RBP4 levels were inversely correlated…. RBP4 is an adipocyte-secreted molecule that is elevated in the serum before the development of frank diabetes and appears to identify insulin resistance and associated cardiovascular risk factors in subjects with varied clinical presentations. These findings provide a rationale for antidiabetic therapies aimed at lowering serum RBP4 levels.>