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

Inabnet, William B; Milone, Luca; Korner, Judith; Durak, Evren; Ahmed, Leaque; Pomrantz, Jill; Harris, Paul E; Bessler, Marc

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 beta-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 beta-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 beta-cell mass in GK rodents and could prove to be an important modality for evaluating beta-cell performance in type 2 diabetes.