title: Glucose-dependent insulinotropic polypeptide has impaired effect on abdominal, subcutaneous adipose tissue metabolism in obese subjects.
abstract: OBJECTIVE
  Glucose-dependent insulinotropic polypeptide (GIP) appears to have a role in lipid metabolism. Recently, we showed that GIP in combination with hyperinsulinemia and hyperglycemia increases triglyceride uptake in abdominal, subcutaneous adipose tissue in lean humans. It has been suggested that increased GIP secretion in obesity will promote lipid deposition in adipose tissue. In light of the current attempts to employ GIP antagonists in the treatment and prevention of human obesity, the present experiments were performed in order to elucidate whether the adipose tissue lipid metabolism would be enhanced or blunted during a GIP, hyperinsulinemic and hyperglycemic (HI-HG) clamp in obese subjects with either normal glucose tolerance (NGT) or impaired glucose tolerance (IGT).
  
  
  METHODS
  Sixteen obese (BMI>30 kg m(-2)) subjects were divided into two groups, based on their plasma glucose response to an oral glucose challenge: (i) NGT and (ii) IGT. Abdominal, subcutaneous adipose tissue lipid metabolism was studied by conducting measurements of arteriovenous concentrations of metabolites and regional adipose tissue blood flow (ATBF) during GIP (1.5 pmol kg(-1) min(-1)) in combination with a HI-HG clamp.
  
  
  RESULTS
  In both groups, ATBF responses were significantly lower than what we have found previously in healthy, lean subjects (P<0.0001). The flow response was significantly lower in the IGT group than in the NGT group (P=0.03). It was not possible to show any increase in the lipid deposition in adipose tissue under the applied experimental conditions and likewise the circulating triglyceride (TAG) concentrations remained constant.
  
  
  CONCLUSIONS
  The applied GIP, HI-HG clamp did not induce any changes in TAG uptake in adipose tissue in obese subjects. This may be due to a blunted increase in ATBF. These experiments therefore suggest that GIP does not have a major role in postprandial lipid metabolism in obese subjects.
authors.affiliation: 1] Department of Clinical Physiology and Nuclear Medicine, Bispebjerg University Hospital, Copenhagen, Denmark [2] Department of Endocrinology and Internal Medicine, Bispebjerg University Hospital, Copenhagen, Denmark [3] Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Asmar
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Simonsen
authors.affiliation: 1] Department of Clinical Physiology and Nuclear Medicine, Bispebjerg University Hospital, Copenhagen, Denmark [2] Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Arngrim
authors.affiliation: 1] Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark [2] The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Xlab, Center for Healthy Ageing, University of Copenhagen, Copenhagen, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Dela
authors.affiliation: 1] Department of Clinical Physiology and Nuclear Medicine, Bispebjerg University Hospital, Copenhagen, Denmark [2] Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Bülow
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D006946:Hyperinsulinism / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D012039:Regional Blood Flow; D050507:Subcutaneous Fat, Abdominal / Q000098:blood supply / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D011964:Receptors, Gastrointestinal Hormone; D014280:Triglycerides; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor