Effects of endogenous GIP in patients with type 2 diabetes.

Abstract

OBJECTIVE:

The insulinotropic effect of exogenous, intravenously infused glucose-dependent insulinotropic polypeptide (GIP) is impaired in patients with type 2 diabetes. We evaluated the effects of endogenous GIP in relation to glucose and bone metabolism in patients with type 2 diabetes using a selective GIP receptor antagonist and hypothesized that the effects of endogenous GIP were preserved.

DESIGN:

A randomized, double-blinded, placebo-controlled, crossover study.

METHODS:

Ten patients with overweight/obesity and type 2 diabetes (mean±s.d.; HbA1c 52 ± 11 mmol/mol; BMI 32.5 ± 4.8 kg/m2) were included. We infused a selective GIP receptor antagonist, GIP(3-30)NH2 (1200 pmol/kg/min), or placebo (saline) during two separate, 230-min, standardized, liquid mixed meal tests followed by a meal ad libitum. Subcutaneous adipose tissue biopsies were analyzed.

RESULTS:

Compared with placebo, GIP(3-30)NH2 reduced postprandial insulin secretion (Δbaseline-subtracted area under the curve (bsAUC)C-peptide% ± s.e.m.; -14 ± 6%, P = 0.021) and peak glucagon (Δ% ± s.e.m.; -11 ± 6%, P = 0.046) but had no effect on plasma glucose (P = 0.692). Suppression of bone resorption (assessed by circulating carboxy-terminal collagen crosslinks (CTX)) was impaired during GIP(3-30)NH2 infusion compared with placebo (ΔbsAUCCTX; ±s.e.m.; -4.9 ± 2 ng/mL × min, P = 0.005) corresponding to a ~50% reduction. Compared with placebo, GIP(3-30)NH2 did not affect plasma lipids, meal consumption ad libitum or adipose tissue triglyceride content.

CONCLUSIONS:

Using a selective GIP receptor antagonist during a meal, we show that endogenous GIP increases postprandial insulin secretion with little effect on postprandial glycaemia but is important for postprandial bone homeostasis in patients with type 2 diabetes.

• Authors: Signe Stensen, Lærke S Gasbjerg, Liva L Krogh, Kirsa Skov-Jeppesen, Alexander H Sparre-Ulrich, Mette H Jensen, Flemming Dela, Bolette Hartmann, Tina Vilsbøll, Jens J Holst, Mette M Rosenkilde, Mikkel B Christensen, Filip K Knop
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 185 Issue 1 Pg. 33-45 (May 21 2021) ISSN: 1479-683X [Electronic] England
• PMID: 33886495 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• Collagen Type I
• Peptide Fragments
• Peptides
• Receptors, Gastrointestinal Hormone
• Triglycerides
• collagen type I trimeric cross-linked peptide
• gastric inhibitory polypeptide (3-30)-amide
• Gastric Inhibitory Polypeptide
• gastric inhibitory polypeptide receptor

Topics

• Adult
• Aged
• Blood Glucose (drug effects, metabolism)
• Bone Resorption (metabolism)
• Collagen Type I (drug effects, metabolism)
• Cross-Over Studies
• Diabetes Mellitus, Type 2 (metabolism)
• Double-Blind Method
• Feeding Behavior (drug effects)
• Gastric Inhibitory Polypeptide (metabolism, pharmacology)
• Humans
• Insulin Secretion (drug effects, physiology)
• Male
• Middle Aged
• Obesity (metabolism)
• Peptide Fragments (pharmacology)
• Peptides (drug effects, metabolism)
• Postprandial Period
• Random Allocation
• Receptors, Gastrointestinal Hormone (antagonists & inhibitors)
• Subcutaneous Fat (drug effects, metabolism)
• Triglycerides (metabolism)