Received September 29, 1998
In his lecture at the Fourth European Congress of Endocrinology, C. R. Kahn considered the effects of knock-out of genes encoding the proteins involved into insulin signal transduction on the development of insulin-resistance and non-insulin-dependent diabetes mellitus. The latter were induced in animals by knock-out of genes encoding insulin receptors and intracellular substrate proteins of the insulin receptor. Using special technology, the authors achieved selective knock-out of the insulin receptor gene in muscles and pancreatic beta-cells of mice. Non-insulin-dependent diabetes mellitus developed only after the knock-out of the insulin receptor gene in beta-cells and resulted from the inability of glucose to penetrate into beta-cells and stimulate insulin secretion. The insensitivity of muscles to insulin due to the lack of its receptor did not result in diabetes. In these animals insulin and glucose blood level did not differ from the control values, but blood lipid concentration was increased. For the cases of the reduction in the insulin-dependent penetration of glucose into muscles, these data may indirectly indicate a transition of energy metabolism in muscles from carbohydrate utilization to increased fat consumption as an energy source.
KEY WORDS: insulin receptor, insulin receptor substrate, non-insulin-dependent diabetes mellitus