title: Validation of [18F]fluorodeoxyglucose and positron emission tomography (PET) for the measurement of intestinal metabolism in pigs, and evidence of intestinal insulin resistance in patients with morbid obesity.
abstract: OBJECTIVE
  The role of the intestine in the pathogenesis of metabolic diseases is gaining much attention. We therefore sought to validate, using an animal model, the use of positron emission tomography (PET) in the estimation of intestinal glucose uptake (GU), and thereafter to test whether intestinal insulin-stimulated GU is altered in morbidly obese compared with healthy human participants.
  
  
  METHODS
  In the validation study, pigs were imaged using [(18)F]fluorodeoxyglucose ([(18)F]FDG) and the image-derived data were compared with corresponding ex vivo measurements in tissue samples and with arterial-venous differences in glucose and [(18)F]FDG levels. In the clinical study, GU was measured in different regions of the intestine in lean (n = 8) and morbidly obese (n = 8) humans at baseline and during euglycaemic hyperinsulinaemia.
  
  
  RESULTS
  PET- and ex vivo-derived intestinal values were strongly correlated and most of the fluorine-18-derived radioactivity was accumulated in the mucosal layer of the gut wall. In the gut wall of pigs, insulin promoted GU as determined by PET, the arterial-venous balance or autoradiography. In lean human participants, insulin increased GU from the circulation in the duodenum (from 1.3 ± 0.6 to 3.1 ± 1.1 μmol [100 g](-1) min(-1), p < 0.05) and in the jejunum (from 1.1 ± 0.7 to 3.0 ± 1.5 μmol [100 g](-1) min(-1), p < 0.05). Obese participants failed to show any increase in insulin-stimulated GU compared with fasting values (NS).
  
  
  CONCLUSIONS
  Intestinal GU can be quantified in vivo by [(18)F]FDG PET. Intestinal insulin resistance occurs in obesity before the deterioration of systemic glucose tolerance.
authors: Turku PET Centre, University of Turku, PL 52, FIN-20520 Turku, Finland.
authors: H
authors: H
authors: Honka
authors: J
authors: J
authors: Mäkinen
authors: J C
authors: JC
authors: Hannukainen
authors: M
authors: M
authors: Tarkia
authors: V
authors: V
authors: Oikonen
authors: M
authors: M
authors: Teräs
authors: V
authors: V
authors: Fagerholm
authors: T
authors: T
authors: Ishizu
authors: A
authors: A
authors: Saraste
authors: C
authors: C
authors: Stark
authors: T
authors: T
authors: Vähäsilta
authors: P
authors: P
authors: Salminen
authors: A
authors: A
authors: Kirjavainen
authors: M
authors: M
authors: Soinio
authors: A
authors: A
authors: Gastaldelli
authors: J
authors: J
authors: Knuuti
authors: P
authors: P
authors: Iozzo
authors: P
authors: P
authors: Nuutila
mesh_terms: D000328:Adult; D000818:Animals; D001158:Arteries / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000493:pharmacokinetics; D006801:Humans; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D011897:Random Allocation; D013552:Swine; D014680:Veins / Q000473:pathology
chemical_list: D019788:Fluorodeoxyglucose F18; D005947:Glucose