In vivo metabolic effects of insulin-like growth factor-I not mediated through the insulin receptor

Nicoletta Dozio, Marina Scavini, Angelo Beretta, Stefano Sartori, Franco Meschi, Elena Sarugeri, Guido Pozza

Research output: Contribution to journalArticle

Abstract

Patients with mutations affecting insulin receptor function may maintain some degree of metabolic control. The hypothesis has been put forth that in these patients, fuels may be metabolized through pathways (i.e. receptor activation) that become relevant in such abnormal conditions. The aim of our study was to evaluate the metabolic effects of insulin-like growth factor-I (IGF-I) in a 19-yr-old patient with homozygous mutation of the insulin receptor α-subunit. Her metabolic and hormonal features were marked hyperglycemia (11-33 mmol/L) and hyperinsulinemia (1000-2000 pmol/L); normal free fatty acids and lactate; low IGF-I; glycerol, alanine, and pyruvate below the normal range; and elevated β-hydroxybutyrate. Unlike diabetic ketoacidosis, no triglyceride or protein breakdown was present, suggesting a compensatory mechanism, possibly sustained by the insulin concentration acting on IGF-I receptors. Subcutaneous administration of IGF-I (40, 80, and 120 μg/kg), although not affecting plasma glucose, resulted in a rapid decrease in free fatty acids and prevented the rise of β-hydroxybutyrate levels compared to placebo. Therefore, IGF-I can exert direct metabolic effects in vivo, probably through activation of its own receptor, even at a concentration not affecting blood glucose levels. Furthermore, these findings are consistent with the hypothesis that IGF-I receptors may be activated by high insulin levels, providing lipid and protein regulation in patients with nonfunctional insulin receptors.

Original languageEnglish
Pages (from-to)1325-1328
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume80
Issue number4
DOIs
Publication statusPublished - Apr 1995

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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