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.
|Heptulla, R A; Tamborlane, W V; Ma, T Y et al. (2001) Oral glucose augments the counterregulatory hormone response during insulin-induced hypoglycemia in humans. J Clin Endocrinol Metab 86:645-8|
|Heptulla, R A; Tamborlane, W V; Cavaghan, M et al. (2000) Augmentation of alimentary insulin secretion despite similar gastric inhibitory peptide (GIP) responses in juvenile obesity. Pediatr Res 47:628-33|
|Attia, N; Caprio, S; Jones, T W et al. (1999) Changes in free insulin-like growth factor-1 and leptin concentrations during acute metabolic decompensation in insulin withdrawn patients with type 1 diabetes. J Clin Endocrinol Metab 84:2324-8|
|Caprio, S (1999) Insulin: the other anabolic hormone of puberty. Acta Paediatr Suppl 88:84-7|
|Maggs, D G; Jacob, R; Rife, F et al. (1997) Counterregulation in peripheral tissues: effect of systemic hypoglycemia on levels of substrates and catecholamines in human skeletal muscle and adipose tissue. Diabetes 46:70-6|
|Heptulla, R A; Boulware, S D; Caprio, S et al. (1997) Decreased insulin sensitivity and compensatory hyperinsulinemia after hormone treatment in children with short stature. J Clin Endocrinol Metab 82:3234-8|
|Girardi, N L; Shaywitz, S E; Shaywitz, B A et al. (1995) Blunted catecholamine responses after glucose ingestion in children with attention deficit disorder. Pediatr Res 38:539-42|