Insulin Metabolic effect

FIGURE 23.22 The metabolic effects of insulin. As described in Chapter 34, binding of insulin to membrane receptors stimulates the protein kinase activity of the receptor. Subsequent phosphorylation of target proteins modulates the effects indicated. 

Antidiabetic Drugs other than Insulin. Figure 3 The antihyperglycaemic effect of metformin involves enhanced insulin-mediated suppression of hepatic glucose production and muscle glucose uptake. Metformin also exerts non-insulin-dependent effects on these tissues, including reduced fatty acid oxidation and increased anaerobic glucose metabolism by the intestine. FA, fatty acid f, increase i decrease. 

Store it while it s here. Insulin binds to a specific receptor on the cell surface and exerts its metabolic effect by a signaling pathway that involves a receptor tyrosine kinase phosphorylation cascade. Note that insulin stimulates storage processes and at the same time inhibits degradative pathways. 

Table 11.1 Some metabolic effects of insulin. These effects are generally countered by other hormones (glucagon and, in some cases, adrenaline). Hence, the overall effect noted often reflects the relative rates of these hormones present in the plasma...

Figure 11.2 Structure of the insulin receptor (a). Binding of insulin promotes autophosphorylation of the (3-subunits, where each (3-subunit phosphorylates the other (3-subunit. Phosphate groups are attached to three specific tyrosine residues (tyrosines 1158, 1162 and 1163), as indicated in (b). Activation of the (3-subunit s tyrosine kinase activity in turn results in the phosphorylation of various intracellular (protein) substrates which trigger the mitogen-activated protein kinase and/or the phosphoinositide (PI-3) kinase pathway responsible for inducing insulin s mitogenic and metabolic effects. The underlying molecular events occurring in these pathways are complex (e.g. refer to Combettes-Souverain, M. and Issad, T. 1998. Molecular basis of insulin action. Diabetes and Metabolism, 24, 477-489)...

Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, Lee CH, Oh WK, Kim CT, Hohnen-Behrens C, Gosby A, Kraegen EW, James DE, Kim JB. (2006) Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistance states. Diabetes 55 2256-2264. 

A). In the obese, the maximum binding possible (plateau of curve) is displaced downward, indicative of the reduction in receptor numbers. Also, at low insulin concentrations, there is less binding of insulin, compared with the control condition. For a given metabolic effect a certain number of receptors must be occupied. As shown by the binding curves (dashed lines), this can still be achieved with a reduced receptor number, although only at a higher concentration of insulin. 

Metabolic Effects. The hyperglycemic effect of nickel is discussed under endocrine effects because it appears to be secondary to the effects on catecholamine release from the adrenal gland and central nervous system and to the effects on insulin release by the pancreas. 

Insulin aspart is absorbed nearly twice as fast as regular insulin. In addition to binding to the insulin receptor, insulin aspart also binds to the insuUnlike growth factor (IGF-1) receptor, which shares structural homology with the insulin receptor. However, at physiological and pharmacological levels, the metabolic effects of insulin aspart predominate. Both lispro insulin and insulin aspart have relatively fast onsets and short... 

D) Glucagon is a hormone that counteracts many of the metabolic effects of insulin. 

Kuperstein R. and Z. Sasson (2000). Effects of antihypertensive therapy on glucose and insulin metabolism and on left ventricular mass. Circulation 102 1802-1806. 

Alpha blockers also produce certain metabolic effects such as inhibitory action of adrenaline on insulin secretion is blocked and adrenaline induced rise in blood potassium level is also blocked. 

Study Questions 23. Metabolic Effects of Insulin and Glucagon... 

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