Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus.

TLDR

In type‑2 diabetes, the overall incretin effect is reduced. The study compared the insulinotropic actions of exogenous GIP and GLP‑1 [7‑36 amide] in nine type‑2 diabetic patients and nine matched normal subjects. Synthetic GIP (0.8 and 2.4 pmol kg⁻¹ min⁻¹) and GLP‑1 [7‑36 amide] (0.4 and 1.2 pmol kg⁻¹ min⁻¹) were infused under hyperglycemic clamp conditions (8.75 mmol L⁻¹) in separate experiments. Both hormones dose‑dependently increased insulin and C‑peptide in both groups, but GIP’s maximal effect was 54 % lower in diabetics, whereas GLP‑1’s effect was 71 % of normal and not significantly different; GLP‑1 also lowered glucagon in both groups, whereas GIP did not, indicating that GLP‑1 retains insulinotropic activity in mild type‑2 diabetes while GIP does not.

Abstract

In type-2 diabetes, the overall incretin effect is reduced. The present investigation was designed to compare insulinotropic actions of exogenous incretin hormones (gastric inhibitory peptide [GIP] and glucagon-like peptide 1 [GLP-1] [7-36 amide]) in nine type-2 diabetic patients (fasting plasma glucose 7.8 mmol/liter; hemoglobin A1c 6.3 +/- 0.6%) and in nine age- and weight-matched normal subjects. Synthetic human GIP (0.8 and 2.4 pmol/kg.min over 1 h each), GLP-1 [7-36 amide] (0.4 and 1.2 pmol/kg.min over 1 h each), and placebo were administered under hyperglycemic clamp conditions (8.75 mmol/liter) in separate experiments. Plasma GIP and GLP-1 [7-36 amide] concentrations (radioimmunoassay) were comparable to those after oral glucose with the low, and clearly supraphysiological with the high infusion rates. Both GIP and GLP-1 [7-36 amide] dose-dependently augmented insulin secretion (insulin, C-peptide) in both groups (P < 0.05). With GIP, the maximum effect in type-2 diabetic patients was significantly lower (by 54%; P < 0.05) than in normal subjects. With GLP-1 [7-36 amide] type-2 diabetic patients reached 71% of the increments in C-peptide of normal subjects (difference not significant). Glucagon was lowered during hyperglycemic clamps in normal subjects, but not in type-2 diabetic patients, and further by GLP-1 [7-36 amide] in both groups (P < 0.05), but not by GIP. In conclusion, in mild type-2 diabetes, GLP-1 [7-36 amide], in contrast to GIP, retains much of its insulinotropic activity. It also lowers glucagon concentrations.