Basal insulin, glucagon, and growth hormone replacement

Suzanne M. Breckenridge, Bharathi Raju, Ana Maria Arbelaez, Bruce W. Patterson, Benjamin A. Cooperberg, Philip E. Cryer

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Conclusions drawn from the pancreatic (or islet) clamp technique (suppression of endogenous insulin, glucagon, and growth hormone secretion with somatostatin and replacement of basal hormone levels by intravenous infusion) are critically dependent on the biological appropriateness of the selected doses of the replaced hormones. To assess the appropriateness of representative doses we infused saline alone, insulin (initially 0.20 mU·kg -1·min-1) alone, glucagon (1.0 ng·kg -1·min-1) alone, and growth hormone (3.0 ng·kg-1·min-1) alone intravenously for 4 h in 13 healthy individuals. That dose of insulin raised plasma insulin concentrations approximately threefold, suppressed glucose production, and drove plasma glucose concentrations down to subphysiological levels (65 ± 3 mg/dl, P < 0.0001 vs. saline), resulting in nearly complete suppression of insulin secretion (P < 0.0001) and stimulation of glucagon (P = 0.0059) and epinephrine (P = 0.0009) secretion. An insulin dose of 0.15 mU·kg -1·min-1 caused similar effects, but a dose of 0.10 mU·kg-1·min-1 did not. The glucagon and growth hormone infusions did not alter plasma glucose levels or those of glucoregulatory factors. Thus, insulin "replacement" doses of 0.20 and even 0.15 mU·kg-1·min-1 are excessive, and conclusions drawn from the pancreatic clamp technique using such doses may need to be reassessed.

Original languageEnglish
Pages (from-to)E1303-E1310
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume293
Issue number5
DOIs
StatePublished - Nov 1 2007

Keywords

  • Octreotide
  • Pancreatic clamp

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