Subcutaneous Injection of the Incretin Hormone Glucagon-Like Peptide 1 Abolishes Postprandial Glycemia in NIDDM

Mark K Gutniak; Birgitta Linde; Jens J Holst; Suad Efendić

doi:10.2337/diacare.17.9.1039

Original Articles

Subcutaneous Injection of the Incretin Hormone Glucagon-Like Peptide 1 Abolishes Postprandial Glycemia in NIDDM

Mark K Gutniak, MD, PHD,
Birgitta Linde, MD, PHD,
Jens J Holst, MD, PHD and
Suad Efendić, MD, PHD

Department of Endocrinology, Karolinska Institute, Stockholm, Sweden
Department of Clinical Physiology, Karolinska Institute, Stockholm, Sweden
Department of Medical Physiology, PANUM Institute, University of Copenhagen, Denmark

Address correspondence and reprint requests to Mark Gutniak, MD, PhD, Department of Endocrinology and Diabetology, Karolinska Institute, 104 01 Stockholm, Sweden.

Diabetes Care 1994 Sep; 17(9): 1039-1044. https://doi.org/10.2337/diacare.17.9.1039

Abstract

OBJECTIVE To investigate the effect of subcutaneously injected glucagon-like peptide 1 (GLP-1) (7–36)amide on postprandial plasma glucose, insulin, and C-peptide levels in patients with non-insulin-dependent diabetes mellitus (NIDDM) and a secondary failure to sulfonylureas.

RESEARCH DESIGN AND METHODS GLP-1 (25 nmol) was injected subcutaneously into either the abdominal wall or the gluteal region at a standardized depth and speed. The injection device was guided by the ultrasound determination of the depth of the fat layer. The peptide was given 5 min before a standard meal. Plasma concentrations of glucose, C-peptide, insulin, glucagon, and GLP-1 were followed during 240 min after the injection.

RESULTS In control experiments, a significant hyperglycemia was attained after the meal. GLP-1 given into the abdominal wall not only virtually abolished the postprandial blood glucose rise but significantly decreased glucose concentrations, with a nadir at ∼25 min after the injection. A rapid rise of C-peptide and insulin levels was observed 10-15 min after the injection of GLP-1. The stimulatory effect of GLP-1 was transient, and, at 45 min after the meal, both insulin and C-peptide levels were almost identical in GLP-1 and control experiments. Significantly lower glucagon concentrations were observed 35-65 min after the peptide injection. GLP-1 concentration in plasma increased from 10 pM to a peak concentration (C_max) of 70 pM at T_max 30 min after injection. Then GLP-1 levels rapidly decreased to 25 pM at 95 min and returned to basal at 215 min. The gluteal injection of GLP-1 had similar effects compared with the abdominal administration on plasma levels of glucose, insulin, C-peptide, and glucagon.

CONCLUSIONS GLP-1 is promptly absorbed from the subcutaneous tissue. It exerts a significant blood glucose lowering effect when administered before meals in overweight patients with NIDDM.