Nonobese diabetic mice have diminished gallbladder motility and shortened crystal observation time

Shannon J. Graewin, James M. Kiely, Keun Ho Lee, Carol L. Svatek, Attila Nakeeb, Henry A. Pitt, Thomas Magnuson, Frank Moody

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Diabetes and obesity are strongly associated and are risk factors for cholesterol gallstone disease. Leptin-deficient and leptin-resistant diabetic obese mice have enlarged, hypomotile gallbladders. In addition, bile from gallbladders of leptin-deficient mice has enhanced cholesterol crystal formation, whereas bile from gallbladders of leptin-resistant mice has delayed crystal observation time. To determine the effect of diabetes alone, we hypothesized that leptin-normal, nonobese diabetic (NOD) mice would have reduced biliary motility and rapid crystal formation. Twenty control and 9 prediabetic and 11 diabetic NOD, 12- to 26-week-old mice underwent glucose measurement and cholecystectomy for muscle bath stimulation with neurotransmitters. An additional group of 200 control and 78 NOD 12-week-old mice underwent microscopic bile examination for cholesterol crystal formation. Compared with control mice, prediabetic NOD mice had similar glucose levels and gallbladder volumes. Diabetic NOD mice had higher sugar levels and larger gallbladder volumes (P < 0.001) than control mice. Prediabetic NOD gallbladders had less contractility (P < 0.01) than control gallbladders, and contractility worsened (P < 0.01) in diabetic NOD mice. NOD mice formed cholesterol crystals earlier than did control mice (P < 0.05). Nonobese diabetic NOD mice have (1) decreased gallbladder contraction to neurotransmitters, which worsens with development of diabetes, and (2) rapid crystal formation. We conclude that diabetes alone alters gallbladder motility and cholesterol crystal formation.

Original languageEnglish (US)
Pages (from-to)824-830
Number of pages7
JournalJournal of Gastrointestinal Surgery
Issue number7
StatePublished - 2004
Externally publishedYes


  • Cholesterol
  • Diabetes mellitus
  • Gallbladder
  • Gallstones
  • Motility

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology


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