PMID- 28073779
OWN - NLM
STAT- MEDLINE
DCOM- 20170626
LR  - 20220316
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Linking)
VI  - 312
IP  - 3
DP  - 2017 Mar 1
TI  - Glucose-dependent insulinotropic polypeptide promotes lipid deposition in 
      subcutaneous adipocytes in obese type 2 diabetes patients: a maladaptive 
      response.
PG  - E224-E233
LID - 10.1152/ajpendo.00347.2016 [doi]
AB  - 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 (n = 6), normoglycemic obese (n 
      = 6), obese with impaired glucose regulation (IGR; n = 6), and obese T2DM (n = 
      5), participated in a double-blind, randomized, crossover study involving a 
      hyperglycemic clamp with a 240-min GIP infusion (2 pmol.kg(-1).min(-1)) 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(0-4 h) +/- SE, 41,992 +/- 9,843 
      micromol.l(-1).min(-1) vs. 71,468 +/- 13,605 with placebo, P = 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, P = 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, r = 0.56, P = 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.
CI  - Copyright (c) 2017 the American Physiological Society.
FAU - Thondam, Sravan K
AU  - Thondam SK
AUID- ORCID: 0000-0002-3675-4168
AD  - Obesity and Endocrinology Research Group, University Hospital Aintree, Liverpool, 
      United Kingdom s.thondam@liverpool.ac.uk.
FAU - Daousi, Christina
AU  - Daousi C
AD  - Obesity and Endocrinology Research Group, University Hospital Aintree, Liverpool, 
      United Kingdom.
FAU - Wilding, John P H
AU  - Wilding JP
AD  - Obesity and Endocrinology Research Group, University Hospital Aintree, Liverpool, 
      United Kingdom.
AD  - Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, 
      United Kingdom.
FAU - Holst, Jens J
AU  - Holst JJ
AD  - NovoNordisk Foundation Center for Basic Metabolic Research and Department of 
      Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
FAU - Ameen, Gulizar I
AU  - Ameen GI
AD  - Department of Cellular and Molecular Physiology University of Liverpool, 
      Liverpool, United Kingdom; and.
FAU - Yang, Chenjing
AU  - Yang C
AD  - Department of Cellular and Molecular Physiology University of Liverpool, 
      Liverpool, United Kingdom; and.
FAU - Whitmore, Catherine
AU  - Whitmore C
AD  - Obesity and Endocrinology Research Group, University Hospital Aintree, Liverpool, 
      United Kingdom.
FAU - Mora, Silvia
AU  - Mora S
AD  - Department of Cellular and Molecular Physiology University of Liverpool, 
      Liverpool, United Kingdom; and.
FAU - Cuthbertson, Daniel J
AU  - Cuthbertson DJ
AD  - Obesity and Endocrinology Research Group, University Hospital Aintree, Liverpool, 
      United Kingdom.
AD  - Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, 
      United Kingdom.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170110
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Blood Glucose)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Incretins)
RN  - 0 (Insulin)
RN  - 0 (Triglycerides)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
SB  - IM
MH  - Adipocytes/drug effects/metabolism
MH  - Adipogenesis/drug effects
MH  - Adult
MH  - Blood Glucose/metabolism
MH  - Case-Control Studies
MH  - Cross-Over Studies
MH  - Diabetes Mellitus, Type 2/complications/*metabolism
MH  - Double-Blind Method
MH  - Esterification/drug effects
MH  - Fatty Acids, Nonesterified/metabolism
MH  - Gastric Inhibitory Polypeptide/*pharmacology
MH  - Glucose Clamp Technique
MH  - Glucose Intolerance/complications/*metabolism
MH  - Humans
MH  - Incretins/*pharmacology
MH  - Insulin/metabolism
MH  - Lipid Metabolism/drug effects
MH  - Lipogenesis/*drug effects
MH  - Male
MH  - Middle Aged
MH  - Obesity/complications/*metabolism
MH  - Subcutaneous Fat/cytology
MH  - Triglycerides/metabolism
OTO - NOTNLM
OT  - adipose tissue
OT  - glucose-dependent insulinotropic polypeptide
OT  - lipid metabolism
OT  - nonesterified fatty acids
OT  - type 2 diabetes
EDAT- 2017/01/12 06:00
MHDA- 2017/06/27 06:00
CRDT- 2017/01/12 06:00
PHST- 2016/09/21 00:00 [received]
PHST- 2016/11/28 00:00 [revised]
PHST- 2017/01/02 00:00 [accepted]
PHST- 2017/01/12 06:00 [pubmed]
PHST- 2017/06/27 06:00 [medline]
PHST- 2017/01/12 06:00 [entrez]
AID - ajpendo.00347.2016 [pii]
AID - 10.1152/ajpendo.00347.2016 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2017 Mar 1;312(3):E224-E233. doi: 
      10.1152/ajpendo.00347.2016. Epub 2017 Jan 10.