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This Article Full Text Full Text (PDF) All Versions of this Article: 293/5/E1303    most recent 00325.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Breckenridge, S. M. Articles by Cryer, P. E. Search for Related Content PubMed PubMed Citation Articles by Breckenridge, S. M. Articles by Cryer, P. E.

Basal insulin, glucagon, and growth hormone replacement

Divisions of ¹Endocrinology, Metabolism, and Lipid Research and ²Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, Missouri

Submitted 25 May 2007 ; accepted in final form 14 August 2007

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.

octreotide; pancreatic clamp