In healthy children, the onset of puberty is marked by a rapid increase in linear growth and change in body composition. However, the mechanisms describing how-the hormonal change of puberty interact to stimulate growth have not been established. Our preliminary studies suggest the hypothesis that the hormonal changes of puberty induce a selective defect in insulin-stimulated glucose metabolism. This defect leads to compensatory hypersecretion of insulin which, in turn, amplifies insulin's anabolic effects on protein and fat metabolism. In the present study, we will use the euglycemic insulin clamp and the hyperglycemic clamp techniques in combination with stable isotope tracer infusions, indirect calorimetry and magnetic resonance imagining in healthy children and adults to comprehensively assess the influence of normal puberty on fuel metabolism body composition. We will also examine how the changes in insulin secretion, insulin action and body composition induced by GH treatment in healthy short children compare to those of normal puberty. Finally, we will examine the hypothesis that GH-insulin interaction may be disturbed in childhood diseases or by treatments that exaggerate insulin resistance or limit compensatory insulin hypersecretion by studying girls with Turner syndrome before and after GH therapy and by studying patients with poorly-controlled insulin-dependent diabetes. These investigations will provide insights and information that is urgently needed now that biosynthetic techniques have made unlimited supplies of GH and other growth promoting peptide available for the treatment of a variety of disorders.
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