Unprecedented high insulin secretion in a healthy human subject after intravenous glucagon-like peptide-1: a case report

Abstract

Background: The gut-derived incretin hormones, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, are released in response to ingestion of nutrients. Both hormones are highly insulinotropic in strictly glucose-dependent fashions and glucagon-like peptide-1 is often referred to as one of the most insulinotropic substances known.

Case presentation: Plasma insulin and C-peptide concentrations were measured in a healthy Caucasian male (age: 53 years; body mass index: 28.6 kg/m2; fasting plasma glucose: 5.7 mM; 2 h plasma glucose value following 75 g-oral glucose tolerance test: 3.5 mM; glycated haemoglobin A1c: 5.5%) during glucagon (1 mg) and meal (2,370 kJ) tests, and during two 2 h 15 mM-hyperglycaemic clamps with continuous intravenous infusion of glucagon-like peptide-1 (1 pmol/kg/min) and glucose-dependent insulinotropic polypeptide (4 pmol/kg/min), respectively. Normal insulin and C-peptide responses were observed during meal test (peak concentrations: 300 and 3,278 pM) and glucagon test (peak concentrations: 250 and 2,483 pM). During the hyperglycaemic clamp with continuous intravenous infusion of GLP-1 the subject exhibited plasma insulin and C-peptide concentrations of 13,770 and 22,380 pM, respectively.

Conclusions: To our knowledge insulin and C-peptide concentrations of these magnitudes have never been reported. Thus, the present data support the view that glucagon-like peptide-1 is one of the most insulinotropic substances known.

Figure 1

Meal test and glucagon test. Plasma glucose (upper panels), insulin (mid panels) and C-peptide (lower panels) concentrations during meal test and glucagon test in a healthy subject with normal glucose tolerance.

Figure 2

Hyperglycaemic clamps with GLP-1/GIP. Plasma glucose (upper panel) and insulin (lower panel) concentrations in a healthy subject with normal glucose tolerance during hyperglycaemic clamps with continuous infusion of glucagon-like peptide-1 (filled triangles) and glucose-dependent insulinotropic polypeptide (open triangles), respectively. The insert in the lower panel illustrates plasma insulin concentrations during the initial 15 min of the two clamps.