Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese type 2 diabetes patients: a maladaptive response


Thondam, Sravan K, Daousi, Christina, Wilding, John PH ORCID: 0000-0003-2839-8404, Holst, Jens J, Ameen, Gulizar I ORCID: 0000-0001-8895-3145, Yang, Chenjing, Whitmore, Catherine, Mora, Silvia and Cuthbertson, Daniel J ORCID: 0000-0002-6128-0822 (2017) Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese type 2 diabetes patients: a maladaptive response. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 312 (3). E224-E233.

[img] Text
Thondam S ajpendo.00347.2016.full.pdf - Author Accepted Manuscript
Download (3MB)

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) beyond its insulinotropic effects may regulate postprandial lipid metabolism. Whereas the insulinotropic action of GIP is known to be impaired in type 2 diabetes mellitus (T2DM), its adipogenic effect is unknown. We hypothesized that GIP is anabolic in human subcutaneous adipose tissue (SAT) promoting triacylglycerol (TAG) deposition through reesterification of nonesterified fatty acids (NEFA), and this effect may differ according to obesity status or glucose tolerance. Twenty-three subjects categorized into four groups, normoglycemic lean (<i>n</i> = 6), normoglycemic obese (<i>n</i> = 6), obese with impaired glucose regulation (IGR; <i>n</i> = 6), and obese T2DM (<i>n</i> = 5), participated in a double-blind, randomized, crossover study involving a hyperglycemic clamp with a 240-min GIP infusion (2 pmol·kg<sup>-1</sup>·min<sup>-1</sup>) or normal saline. Insulin, NEFA, SAT-TAG content, and gene expression of key lipogenic enzymes were determined before and immediately after GIP/saline infusions. GIP lowered NEFA concentrations in the obese T2DM group despite diminished insulinotropic activity (mean NEFA AUC<sub>0-4 h</sub> ± SE, 41,992 ± 9,843 µmol·l<sup>-1</sup>·min<sup>-1</sup> vs. 71,468 ± 13,605 with placebo, <i>P</i> = 0.039, 95% CI: 0.31-0.95). Additionally, GIP increased SAT-TAG in obese T2DM (1.78 ± 0.4 vs 0.86 ± 0.1-fold with placebo, <i>P</i> = 0.043, 95% CI: 0.1-1.8). Such effect with GIP was not observed in other three groups despite greater insulinotropic activity. Reduction in NEFA concentration with GIP correlated with adipose tissue insulin resistance for all subjects (Pearson, <i>r</i> = 0.56, <i>P</i> = 0.005). There were no significant gene expression changes in key SAT lipid metabolism enzymes. In conclusion, GIP appears to promote fat accretion and thus may exacerbate obesity and insulin resistance in T2DM.

Item Type: Article
Uncontrolled Keywords: glucose-dependent insulinotropic polypeptide, type 2 diabetes, adipose tissue, lipid metabolism, nonesterified fatty acids
Depositing User: Symplectic Admin
Date Deposited: 12 Jan 2017 16:24
Last Modified: 19 Jan 2023 07:20
DOI: 10.1152/ajpendo.00347.2016
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3005210
Dimensions
Altmetric
CORE (COnnecting REpositories)