Brown Adipose Tissue: A Potential Site for Islet Transplantation

Abstract

Background. Islet transplantation is a promising treatment in patients with complicated diabetes. The ideal transplant site that can extend islet graft survival and reduce the required number of engrafted islets remains to be established. Methods. Donor islets were isolated from red fluorescent protein (RFP+) mice and transplanted into interscapular brown adipose tissue (BAT) or unilateral inguinal white adipose tissue of age-matched diabetic RFP-mice. Blood glucose and body weight of the mice were monitored, and vitality and function of ectopic RFP+islets were detected by fluorescence imaging, histological examination, and intraperitoneal glucose tolerance test (GTT). Results. BAT enabled the marginal number of grafted islets (80 islets) to restore blood glucose, insulin level, and GTT to normal values in all diabetic recipient mice in the short term after graft, and maintained these values for 1 year at the end of the experiment. Importantly, in the short term after transplantation, abundant extra- and intraislet neovasculatures were observed in BAT, but not in white adipose tissue, which allowed the ectopic islets to retain typical architecture and morphology and contributed to the normal GTT. Moreover, the islet-engrafted BAT displayed normal structure and morphology without significant immunocyte infiltration, and the recipient mice also showed normal lipid levels in the blood. Conclusions. BAT remarkably enhances the viability and biological function of the transplanted ectopic islets. Moreover, the anatomical location of BAT lends itself to biopsy, removal, and islet retransplantation, which strongly suggests the BAT as a potential desirable site for islet transplantation in basic and clinical research.