Submitted on July 13, 2007
Accepted on September 19, 2007
Determination of gastric emptying in non-obese diabetic mice
Kyoung Moo Choi1, Jin Zhu1, Gary J. Stoltz1, Steven Vernino2, Michael Camilleri3, Joseph H. Szurszewski4, Simon J Gibbons1, and Gianrico Farrugia5*
1 Enteric NeuroScience Program, Mayo Clinic, Rochester, Minnesota, United States
2 Department of Neurology, UT SOuthwestern Medical Center, Rochester, Minnesota, United States
3 Mayo Clinic, United States; Enteric NeuroScience Program, Mayo Clinic, Rochester, Minnesota, United States
4 Department of Physiology & Biophysics, Mayo Clinic and Foundation, Rochester,, Minnesota, United States
5 Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, United States
* To whom correspondence should be addressed. E-mail: farrugia.gianrico{at}mayo.edu.
Animal studies on diabetic gastroparesis are limited by inability to follow gastric emptying changes in the same mouse. The study aim was to validate a non-lethal gastric emptying method in NOD LtJ mice, a model of type 1 diabetes and study sequential changes with age and early diabetic status. The reliability and responsiveness of a [13C]-octanoic acid breath test in NOD LtJ mice was tested and the test used to measure solid gastric emptying in NOD LtJ mice and NOR LtJ mice. The [13C]-breath test produced results similar to post mortem recovery of a meal. Bethanechol accelerated gastric emptying (control; 92±9 min, bethanechol; 53±3 min, mean T1/2±SEM) and atropine slowed gastric emptying (control 92±9 min, atropine: 184 ± 31 min, mean T1/2±SEM). Normal gastric emptying (T1/2) in non-diabetic NOD LtJ mice (8-12 wks) was 91 ± 2 min. Aging had differing effects on gastric emptying in NOD LtJ and NOR LtJ mice. Onset of diabetes was accompanied by accelerated gastric emptying during weeks 1-2 of diabetes. Gastric emptying returned to normal by weeks 3-5 with no delay. The [13C]-octanoic acid breath test accurately measures gastric emptying in NOD LtJ mice, is useful to study the time course of changes in gastric emptying in diabetic NOD LtJ mice and is able to detect acceleration in gastric emptying early in diabetes. Opposing changes in gastric emptying between NOD LtJ and NOR LtJ mice suggest that NOR LtJ mice are not good controls for the study of gastric emptying in NOD LtJ mice.
