title: Pancreatic metabolism, blood flow, and β-cell function in obese humans.
abstract: BACKGROUND
  Glucolipotoxicity is believed to induce pancreatic β-cell dysfunction in obesity. Previously, it has not been possible to study pancreatic metabolism and blood flow in humans.
  
  
  OBJECTIVE
  The objective of the study was to investigate whether pancreatic metabolism and blood flow are altered in obesity using positron emission tomography (PET). In the preclinical part, the method was validated in animals.
  
  
  METHODS
  This was a cross-sectional study.
  
  
  METHODS
  The study was conducted in a clinical research center.
  
  
  METHODS
  Human studies consisted of 52 morbidly obese and 25 healthy age-matched control subjects. Validation experiments were done with rodents and pigs.
  
  
  METHODS
  PET and magnetic resonance imaging studies using a glucose analog ([(18)F]fluoro-2-deoxy-d-glucose), a palmitate analog [14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid], and radiowater ([(15)O]H2O) were performed. In animals, a comparison between ex vivo and in vivo data was performed.
  
  
  METHODS
  Pancreatic glucose/fatty acid (FA) uptake, fat accumulation, and blood flow parameters of β-cell function were measured.
  
  
  RESULTS
  PET proved to be a feasible method to measure pancreatic metabolism. Compared with healthy participants, obese participants had elevated pancreatic FA uptake (P < .0001), more fat accumulation (P = .0001), lowered glucose uptake both during fasting and euglycemic hyperinsulinemia, and blunted blood flow (P < .01) in the pancreas. Blood flow, FA uptake, and fat accumulation were negatively associated with multiple markers of β-cell function.
  
  
  CONCLUSIONS
  Obesity leads to changes in pancreatic energy metabolism with a substrate shift from glucose to FAs. In morbidly obese humans, impaired pancreatic blood flow may contribute to β-cell dysfunction and in the pathogenesis of type 2 diabetes.
authors: Turku PET Centre (H.H., J.C.H., M.T., H.K., V.S., K.M., V.O., M.H.-S., A.R., R.P., P.N.), University of Turku, Turku 20520, Finland; Division of Digestive Surgery and Urology (P.S.) and Department of Endocrinology (P.N., M.S.), Turku University Hospital, Turku 20520, Finland; Faculty of Medicine (N.K.), University of Kagawa, Kagawa 760-0016, Japan; Department of Radiology (R.P.), University of Tampere, Tampere 33014, Finland; Institute of Biomedical Engineering (P.I.), National Research Council, 35128 Padua, Italy; and Institute of Clinical Physiology (P.I.), National Research Council, 56124 Pisa, Italy.
authors: Henri
authors: H
authors: Honka
authors: Jarna C
authors: JC
authors: Hannukainen
authors: Miikka
authors: M
authors: Tarkia
authors: Henry
authors: H
authors: Karlsson
authors: Virva
authors: V
authors: Saunavaara
authors: Paulina
authors: P
authors: Salminen
authors: Minna
authors: M
authors: Soinio
authors: Kirsi
authors: K
authors: Mikkola
authors: Nobu
authors: N
authors: Kudomi
authors: Vesa
authors: V
authors: Oikonen
authors: Merja
authors: M
authors: Haaparanta-Solin
authors: Anne
authors: A
authors: Roivainen
authors: Riitta
authors: R
authors: Parkkola
authors: Patricia
authors: P
authors: Iozzo
authors: Pirjo
authors: P
authors: Nuutila
mesh_terms: D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism* / Q000503:physiopathology*; D010179:Pancreas / Q000098:blood supply* / Q000378:metabolism*; D012039:Regional Blood Flow; D013552:Swine