A rodent model of metabolic surgery for study of type 2 diabetes and positron emission tomography scanning of beta cell mass

Abstract Background Type 2 diabetes mellitus is a worldwide healthcare problem with major socioeconomic implications. Metabolic surgical procedures have been shown to improve diabetes, but the mechanism of action is poorly understood. The Goto-Kakizaki (GK) rodent is a type 2 diabetic animal model t...

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Published inSurgery for obesity and related diseases Vol. 5; no. 2; pp. 212 - 217
Main Authors Inabnet, William B., M.D, Milone, Luca, M.D, Korner, Judith, M.D., Ph.D, Durak, Evren, M.D, Ahmed, Leaque, M.D, Pomrantz, Jill, D.V.M, Harris, Paul E., M.D, Bessler, Marc, M.D
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.03.2009
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Summary:Abstract Background Type 2 diabetes mellitus is a worldwide healthcare problem with major socioeconomic implications. Metabolic surgical procedures have been shown to improve diabetes, but the mechanism of action is poorly understood. The Goto-Kakizaki (GK) rodent is a type 2 diabetic animal model that is ideally situated for studying the effect of surgery on diabetes; however, the operative mortality is high. The aim of this study was to describe the operative technique, improvements in perioperative management, and the technique of micro-positron emission tomography (PET) scanning of the β-cell mass in GK rodents. Methods A total of 53 GK rats were divided into 1 of 3 operative groups: sham, sleeve gastrectomy, and duodenojejunal bypass. A subset of animals underwent micro-PET scanning with [11C]-dihydrotetrabenazine to determine the vesicular monoamine transporter 2 binding index, an indicator of β-cell mass. Results The 30-day mortality in the sham and sleeve gastrectomy rodents was 0; however, 2 sleeve gastrectomy rodents developed enterocutaneous fistula and 1 developed an abscess. In the duodenojejunal bypass group, the initial mortality rate was close to 90%; however, refinements in the surgical technique and perioperative management (fluids, antibiotics, pain control) lowered the mortality rate to 60%. The surgical technique is discussed in detail. [11C]-Dihydrotetrabenazine uptake in the pancreas was demonstrated on micro-PET scanning in the sham and duodenojejunal bypass rodents. Conclusion Intensive medical management in the perioperative period and attention to the operative technique lowered the mortality. [11C]-Dihydrotetrabenazine micro-PET scanning is a feasible method for assessing the β-cell mass in GK rodents and could prove to be an important modality for evaluating β-cell performance in type 2 diabetes.
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ISSN:1550-7289
1878-7533
DOI:10.1016/j.soard.2008.09.007