Antidiabetic Agents: Recent Advances in their Molecular and by Bernard Testa, Urs A. Meyer

By Bernard Testa, Urs A. Meyer

Quantity 27, the 1st thematic quantity within the sequence, offers an outline of current wisdom in regards to the pharmacological and scientific points of antidiabetic medications. It goals to stimulate additional attention of attainable recommendations within the improvement of recent antidiabetic medications.

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HGP still remains within normal range because of the suppressive effect of hyperglycaemia. Tissue glucose uptake, however, is markedly reduced. In diabetic subjects, the glucose uptake of muscle tissue is delayed and retarded. While in control subjects muscle glucose uptake accounts for 75% of the total glucose uptake, normal-weight NIDDM patients have a 50% reduction in insulin-mediated peripheral glucose uptake. Thus in the early stages of NIDDM, the site of insulin resistance is not at the level of the liver.

2 CLINICAL SYMPTOMS The onset of the autoimmune disease Type-I diabetes has a protracted prodromal period. Overt symptoms such as hyperglycaemia occur only months and years after initial metabolic and immunological abnormalities such as impaired glucose tolerance, ICA and IAA are noted. Chances of detecting early symptomatic Type-I diabetic patients therefore depend on glucose studies of relatives and monitoring of a combination of immunological serum parameters and assessment of insulin secretion in persons who are at high risk.

Since at the post-kinase level tyrosine phosphorylation of substrate proteins is involved in insulin signalling, an important role for tyrosine phosphatases in the regulation of post-kinase signalling mechanisms has to be assumed (Goldstein, 1992). Tyrosine-specific phosphatases must be involved in the regulation of the autophosphorylation status of the insulin receptor controlling its signalling activity. The same mechanism is likely to be relevant for IRS-1 and other tyrosine-phosphorylated signal-transduction elements.

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