Insulin and growth hormone: regulation of adipocyte metabolism during infancy and childhood

University dissertation from Stockholm : Karolinska Institutet, -

Abstract: The aim of the present investigation was to investigate the role of insulin and growth (GH) in adipose tissue metabolism during development. Lipolysis and lipogenesis were studied in isolated adipocytes from humans and rats of various ages. Human abdominal adipose tissue samples were obtained during elective surgery or by needle lispiration, while epididymal adipose tissue samples were obtained from rats. There was no age-dependent variation in insulin-receptor RNA expression or antilipolytic effect of insulin. However, I rate of basal lipogenesis was approximately three times higher in infants and children than adults, while insulin stimulated lipogenesis was two times higher in infants than in children and adults. In rats, basal and insulin stimulated lipogenesis were two times higher in weaned than in adult animals. No age-dependent variation in insulin sensitivity was observed in human adipocytes, whereas adipocytes from weaned rats were more insulin sensitive I adipocytes from adult animals. The high rate of lipogenesis early in life is probably important factor for age-dependent expansion of the adipose tissue. The mechanism behind this phenomenon is yet unclear, as there was no variation in the glucose transporter (GLUT1 and GLUT4) expression. Plasma and adipose tissue interstitial glucose dynamics was investigated in six children blood sampling and microdialysis during an arginine-insulin tolerance test. After a rapidly induced hypoglycemia, the rebound of interstitial glucose was significantly delayed compared to plasma, and the antilipolytic effect of hyperinsulinemia was opposed by the hypoglycemic stress response. Thus, when continuos microdialysis is used for monitoring children at risk developing hypoglycemia, a prompt blood glucose determination is indicated when I dialysate glucose is low. The effects of systemic GH treatment were investigated in isolated adipocytes and in vivo. GH treatment upregulated GH-receptor RNA expression in children with Prader-Willi (PWS) as well as in children and adults with GH deficiency. Furthermore, insulin lipogenesis increased during treatment in children with PWS, but not significantly in w&)iq obese prepubertal boys. In the latter, treatment reduced body fat percentage, possibly 'A' stimulation of cathecholamine-induced lipolysis, without negative effects on whole I body glucose homeostasis. The putative role for long-term GH treatment of severely obese children requires further investigation.

  This dissertation MIGHT be available in PDF-format. Check this page to see if it is available for download.