title: Basal insulin, glucagon, and growth hormone replacement.
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.
authors: Division of Endocrinology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors: Suzanne M
authors: SM
authors: Breckenridge
authors: Bharathi
authors: B
authors: Raju
authors: Ana Maria
authors: AM
authors: Arbelaez
authors: Bruce W
authors: BW
authors: Patterson
authors: Benjamin A
authors: BA
authors: Cooperberg
authors: Philip E
authors: PE
authors: Cryer
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007773:Lactates / Q000097:blood; D008297:Male; D010191:Pancreatic Polypeptide / Q000097:blood
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates; D019382:Human Growth Hormone; D010191:Pancreatic Polypeptide; D002097:C-Reactive Protein; D005934:Glucagon; D006854:Hydrocortisone; D004837:Epinephrine