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Metabolic Actions of IGF-I in Normal Physiology and Diabetes

Metabolic Actions of IGF-I in Normal Physiology and Diabetes.


IGF-I is ancestorally related to proinsulin and therefore retains some physiological effects that complement the ability of insulin to stimulate glucose uptake.

Furthermore the actions of IGF-I are coordinately regulated with GH thus enabling organisms to breakdown fat and utilize this as a substrate to meet the energy needs that are required for new growth as well as to coordinate their effects for stimulation of protein synthesis and an anabolic response. Therefore IGF-I plays an integral role in coordinating the response to nutrient intake and in initiating the appropriate metabolic changes that enable cells to tolerate a variety of stressful stimuli and resist apoptosis as well as initiate the tissue repair response that occurs after injury. Furthermore it plays an important role in facilitating adaption to major changes in nutrient intake. In this way IGF-I coordinates the response of the three hormones to form a functional unit thereby coordinating nutrient availability and tissue growth. In obesity and metabolic syndrome as well as in patients with overt diabetes the metabolic actions of IGF-I are altered significantly. Similarly its ability to coordinate its functions with those of GH and insulin is impaired in this pathophysiologic state and this constitutes an important component of the maladaptive response of all 3 hormones to metabolic stress.

In conclusion, our results show that IGF-I per se is a potent anticatabolic agent (as in regard to protein metabolism) leading by way of partial inhibition of insulin secretion to increased lipolysis and fat oxidation. These effects of IGF-I are indepenedent of the inhibitory effect on growth hormone secretion. All these effects of IGF-1 are, however, synergistic to those of GH, which stimulates lipolysis and possibly protein anabolism through mechanisms different from those of IGF-1. In the case of simultaneous administration of GH and IGF-1, insulin levels lie between those attained by IGF-I treatment alone and those observed during GH treatment. Since insulin is an important anabolic hormone (41), it is conceivable that in situations of severe catabolism a combination of GH and IGF-I together will turn out to give the best results with regard to anticatabolism and anabolism (40).


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