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

https://doi.org/10.1016/j.soard.2008.09.007Get rights and content

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.

Section snippets

Rodents

The Institutional Animal Care and Use Committee of the Columbia University College of Physicians and Surgeons approved the study protocol. A total of 53 male GK rats (Taconic Laboratory, Hudson, NY) were used for this study. On arrival at the Animal Care Facility of Columbia University, the rats were 10–12 weeks old and weighed 290–320 g. The rats were housed 2 per cage in a 12-hour dark/light cycle room that was maintained at a temperature of 26°C. The rodents were allowed to acclimate for 7

Surgery

Of the 53 rodents, 10 underwent a sham operation, 10 SG, and 33 DJB. No morbidity or mortality occurred in the sham group. In the SG group, 2 rodents developed an enterocutaneous fistula that responded to conservative management. One developed an abdominal wall abscess that did not respond to incision and drainage and antibiotics; this rodent was euthanized 32 days after surgery. At necropsy, multiple small abscesses in the peritoneal cavity were visualized.

A total of 33 animals underwent DJB.

Discussion

T2DM is a chronic disease for which there is no medical cure. Medical treatment of T2DM centers on dietary modification, increased physical activity, and administration of oral pharmaceutical agents and/or insulin or a combination of these interventions. In a randomized controlled trial comparing dietary, sulfonylurea, metformin, and insulin treatment for T2DM, only 25% of patients were able to achieve a glycosylated hemoglobin <7% at 9 years after treatment initiation [15]. It has long been

Conclusion

The GK rodent model of T2DM is well suited for the study of metabolic surgery. However, GK rodents are extremely fragile and must be handled with great care. A comprehensive perioperative management protocol can help lower the operative mortality. [11C]-DTBZ micro-PET scanning is feasible in rodents with T2DM; however, additional study is needed to determine the accuracy of this functional imaging modality.

Disclosures

W. B. Inabnet, Covidien (research grant, Clinical Advisory Board, fellowship support); Marc Bessler, Covidien (consultant, fellowship support).

References (20)

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This study was funded by a research grant from Covidien Healthcare and a research start-up grant from the Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York

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