*Purpose: While islet transplantation is recognized as a promising therapeutic option for severe diabetes mellitus (DM), especially type 1 DM, it still faces to various unresolved problems. One of the major problems is establishment of optimal transplant site. Liver is a current major target for clinical islet transplantation. However, it is known that liver harbors a harsh environment for transplanted islets, which are constructed by instant blood-mediated inflammatory reaction (IBMIR), liver-resident natural killer (NK) cells and ischemia/hypoxia. White adipose tissue (WAT) is one of the candidates as an alternative islet transplant site. Especially, greater omentum has been used for preclinical and clinical studies. However, the mechanism how the transplanted islets engrafted into WAT is not fully discussed. In this study, we attempted to clarify the therapeutic effect of WAT-covered islet transplantation and the mechanism in engraftments.

*Methods: Two hundred rodent (C57BL/6J male mice) islets were placed on the epididymal WAT of syngeneic diabetic recipient mice and covered using it without suturing and usage of biobinding agents (WAT-covered group). As a control, mice which received intraperitoneal and renal subcapsular islet transplantation (Control and Renal subcapsular groups, respectively) using the same numbers of islets were prepared. The therapeutic effects were assessed among the three groups.

*Results: The transplant efficacy of WAT-covered group was significantly superior to Control group and almost equal to Renal subcapsular group in changes of blood glucose and plasma insulin levels after transplantation and change of blood glucose level in glucose tolerance test at two months after transplantation. The number of engrafted islets was significantly increased in WAT-covered group in comparison with Control group. Interestingly, vessel density in engrafted islets in WAT-covered group was more prominent than in Renal subcapsular group whereas the density and expressions of angiogenic factors (Vegfa, b and c) in WAT were poor comparing with abdominal wall and kidney. Adiponectin, a cytokine released from adipose tissue, is considered that a key factor for promotion of islet engraftment into WAT. We revealed that the incubation of adiponectin stimulated expressions of angiogenic (Vegfa, b and c) and adhesion factors (Fn1, Itgb1 and 2) in isolated islets.

*Conclusions: WAT is considered as a useful islet transplant site. Adiponectin plays a pivotal role in engraftment of islets into WAT.

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