Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide I (7–36) amide in type I diabetic patients

WOC Creutzfeldt, N Kleine, B Willms, C Ørskov… - Diabetes …, 1996 - Am Diabetes Assoc
WOC Creutzfeldt, N Kleine, B Willms, C Ørskov, JJ Holst, MA Nauck
Diabetes care, 1996Am Diabetes Assoc
OBJECTIVE Glucagon-like peptide I (7–36) amide (GLP-1) is a physiological incretin
hormone that, in slightly supraphysiological doses, stimulates insulin secretion, lowers
glucagon concentrations, and thereby normalizes elevated fasting plasma glucose
concentrations in type II diabetic patients. It is not known whether GLP-1 has effects also in
fasting type I diabetic patients. RESEARCH DESIGN AND METHODS In 11 type I diabetic
patients (HbA1c 9.1±2.1%; normal, 4.2–6.3%), fasting hyperglycemia was provoked by …
OBJECTIVE
Glucagon-like peptide I(7–36) amide (GLP-1) is a physiological incretin hormone that, in slightly supraphysiological doses, stimulates insulin secretion, lowers glucagon concentrations, and thereby normalizes elevated fasting plasma glucose concentrations in type II diabetic patients. It is not known whether GLP-1 has effects also in fasting type I diabetic patients.
RESEARCH DESIGN AND METHODS
In 11 type I diabetic patients (HbA1c 9.1 ± 2.1%; normal, 4.2–6.3%), fasting hyperglycemia was provoked by halving their usual evening NPH insulin dose. In random order on two occasions, 1.2 pmol · kg−1 · min−1 GLP-1 or placebo was infused intravenously in the morning (plasma glucose 13.7 ± 0.9 mmol/l; plasma insulin 26 ± 4 pmol/l). Glucose (glucose oxidase method), insulin, C-peptide, glucagon, GLP-1, cortisol, growth hormone (immunoassays), triglycerides, cholesterol, and nonesterified fatty acids (enzymatic tests) were measured.
RESULTS
Glucagon was reduced from ∼8 to 4 pmol/l, and plasma glucose was lowered from 13.4 ± 1.0 to 10.0 ± 1.2 mmol/l with GLP-1 administration (plasma concentrations ∼100 pmol, P < 0.0001), but not with placebo (14.2 ± 0.7 to 13.2 ± 1.0). Transiently, C-peptide was stimulated from basal 0.09 ± 0.02 to 0.19 ± 0.06 nmol/l by GLP-1 (P < 0.0001), but not by placebo (0.07 ± 0.02 to 0.07 ± 0.02). There was no significant effect on nonesterified fatty acids (P = 0.34), triglycerides (P = 0.57), cholesterol (P = 0.64), cortisol (P = 0.40), or growth hormone (P = 0.53).
CONCLUSIONS
Therefore, exogenous GLP-1 is able to lower fasting glycemia also in type I diabetic patients, mainly by reducing glucagon concentrations. However, this alone is not sufficient to normalize fasting plasma glucose concentrations, as was previously observed in type II diabetic patients, in whom insulin secretion (C-peptide response) was stimulated 20-fold.
Am Diabetes Assoc