The Role of Insulin in Glucose Metabolism

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Diabetes mellitus (DM) is defined as a disease that results in chronic hypergly-caemia due to an absolute or relative lack of insulin and/or insulin resistance, which in turn impairs glucose, protein and lipid metabolism, and finally entrains the characteristic secondary complications.17 According to the definition of WHO, DM is generally classified as either insulin-dependent (IDDM, type 1) or non-insulin-dependent (NIDDM, type 2).18 To treat NIDDM several synthetic organic therapeutics have already been clinically used involving sul-phonylureas, sulphonamides, biguanides and triglydazone, which has recently been developed. However, IDDM can be controlled only by daily injections of insulin.

Insulin is a signalling hormone, which is essential for the metabolism of both carbohydrate and fat. It is secreted by the pancreas in response to elevated levels of glucose in the bloodstream. The increased insulin level then normally promotes glucose uptake by the liver and gut as well as by peripheral tissues (adipose and muscle), which results in energy production and storage as needed by the organism.19

The insulin receptor (IR) is an insulin-activated trans-membrane protein-tyrosine-kinase. Following insulin binding, the receptor undergoes activation by autophosphorylation and subsequently phosphorylates several endogenous proteins on tyrosine moieties. Tyrosyl phosphorylation is linked to a serine/ threonine phosphorylation state of key enzymatic systems controlling the glucose and fat metabolism. When insulin is removed, termination occurs at several levels, one of which is dephosphorylation of tyrosyl residues by endogenous protein phosphotyrosine phosphatases (PTPase).20

Since vanadate is an inhibitor of phosphatases,21 it was initially believed that vanadate acts intracellularly by blocking the protein phosphotyrosine phos-phatases, acting at the IR and therefore activating it in an insulin-independent manner. However, this turned out not to be the case (see p. 153).

The promotion of glucose uptake in a tissue-specific manner can be enhanced by vanadium. Vanadium compounds, however, can never completely substitute for insulin. (The complete lack of insulin precludes the effectiveness of any vanadium compound.) Nevertheless, many of the observed in vitro and in vivo effects of vanadium are insulin-like.21

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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