Ileal Interposition Surgery Improves Glucose and Lipid Metabolism and Delays Diabetes Onset in the UCD-T2DM Rat

Bethany P. Cummings, April D. Strader, Kimber Stanhope, James L. Graham, Jennifer Lee, Helen E Raybould, Denis G. Baskin, Peter J Havel

Research output: Contribution to journalArticle

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Abstract

Background & Aims: 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-17-36) 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-17-36 and PYY and improvements of insulin sensitivity, β-cell function, and lipid metabolism.

Original languageEnglish (US)
JournalGastroenterology
Volume138
Issue number7
DOIs
StatePublished - Jun 2010

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Lipid Metabolism
Type 2 Diabetes Mellitus
Glucose
Peptide YY
Glucose Tolerance Test
Fats
Lower Gastrointestinal Tract
Insulin
Anatomic Models
Lipids
Food
Bariatric Surgery
Adiposity
Adipocytes
Insulin Resistance
Animal Models
Body Weight
Peptides

Keywords

  • Bariatric Surgery
  • Diabetes Prevention
  • Glucagon-Like Peptide-1
  • Peptide-YY

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Ileal Interposition Surgery Improves Glucose and Lipid Metabolism and Delays Diabetes Onset in the UCD-T2DM Rat. / Cummings, Bethany P.; Strader, April D.; Stanhope, Kimber; Graham, James L.; Lee, Jennifer; Raybould, Helen E; Baskin, Denis G.; Havel, Peter J.

In: Gastroenterology, Vol. 138, No. 7, 06.2010.

Research output: Contribution to journalArticle

Cummings, Bethany P. ; Strader, April D. ; Stanhope, Kimber ; Graham, James L. ; Lee, Jennifer ; Raybould, Helen E ; Baskin, Denis G. ; Havel, Peter J. / Ileal Interposition Surgery Improves Glucose and Lipid Metabolism and Delays Diabetes Onset in the UCD-T2DM Rat. In: Gastroenterology. 2010 ; Vol. 138, No. 7.
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AU - Cummings, Bethany P.

AU - Strader, April D.

AU - Stanhope, Kimber

AU - Graham, James L.

AU - Lee, Jennifer

AU - Raybould, Helen E

AU - Baskin, Denis G.

AU - Havel, Peter J

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AB - Background & Aims: 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-17-36) 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-17-36 and PYY and improvements of insulin sensitivity, β-cell function, and lipid metabolism.

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KW - Diabetes Prevention

KW - Glucagon-Like Peptide-1

KW - Peptide-YY

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