Ileal interposition surgery improves glucose and lipid metabolism and delays diabetes onset in the UCD-T2DM rat.
OBJECTIVE
Bariatric surgery has been shown to reverse type 2 diabetes; however, mechanisms by which this occurs remain undefined. Ileal interposition (IT) is a surgical model that isolates the effects of increasing delivery of unabsorbed nutrients to the lower gastrointestinal tract. In this study we investigated effects of IT surgery on glucose tolerance and diabetes onset in UCD-T2DM (University of California at Davis type 2 diabetes mellitus) rats, a polygenic obese animal model of type 2 diabetes.


METHODS
IT or sham surgery was performed on 4-month-old male UCD-T2DM rats. All animals underwent oral glucose tolerance testing (OGTT). A subset was killed 2 months after surgery for tissue analyses. The remainder was followed until diabetes onset and underwent oral fat tolerance testing (OFTT).


RESULTS
IT surgery delayed diabetes onset by 120 +/- 49 days compared with sham surgery (P < .05) without a difference in body weight. During OGTT, IT-operated animals exhibited lower plasma glucose excursions (P < .05), improved early insulin secretion (P < .01), and 3-fold larger plasma glucagon-like peptide-1(7-36) (GLP-1(7-36)) excursions (P < .001), and no difference in glucose-dependent insulinotropic polypeptide responses compared with sham-operated animals. Total plasma peptide YY (PYY) excursions during OFTT were 3-fold larger in IT-operated animals (P < .01). IT-operated animals exhibited lower adiposity (P < .05), smaller adipocyte size (P < .05), 25% less ectopic lipid deposition, lower circulating lipids, and greater pancreatic insulin content compared with sham-operated animals (P < .05).


CONCLUSIONS
IT surgery delays the onset of diabetes in UCD-T2DM rats which may be related to increased nutrient-stimulated secretion of GLP-1(7-36) and PYY and improvements of insulin sensitivity, beta-cell function, and lipid metabolism.
Cummings
Bethany P
BP
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California 95616, USA.
Strader
April D
AD
Stanhope
Kimber L
KL
Graham
James L
JL
Lee
Jennifer
J
Raybould
Helen E
HE
Baskin
Denis G
DG
Havel
Peter J
PJ
D017667:Adipocytes / Q000473:pathology; D052242:Adiponectin / Q000097:blood; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D015390:Gastric Bypass; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007082:Ileum / Q000601:surgery*; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism; D008297:Male; D019894:Peptide YY / Q000378:metabolism; D051381:Rats; D015431:Weight Loss
D052242:Adiponectin; D007328:Insulin; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1; D005947:Glucose