Small islets transplantation superiority to large ones: implications from islet microcirculation and revascularization.
Pancreatic islet transplantation is a promising therapy to regain glycemic control in diabetic patients. The selection of ideal grafts is the basis to guarantee short-term effectivity and longevity of the transplanted islets. Contradictory to the traditional notion, recent findings implied the superiority of small islets for better transplantation outcomes rather than the large and intact ones. However, the mechanisms remain to be elucidated. Recent evidences emphasized the major impact of microcirculation on islet β -cell mass and function. And potentials in islet graft revascularization are crucial for their survival and preserved function in the recipient. In this study, we verified the distinct histological phenotype and functionality of small islets versus large ones both in vitro and in vivo. With efforts to exploring the differences in microcirculation and revascularization of islet grafts, we further evaluated local expressions of angiotensin and vascular endothelial growth factor A (VEGF-A) at different levels. Our findings reveal that, apart from the higher density of insulin-producing β -cells, small islets express less angiotensin and more angiotrophic VEGF-A. We therefore hypothesized a logical explanation of the small islet superiority for transplantation outcome from the aspects of facilitated microcirculation and revascularization intrinsically in small islets.
Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China.
Wenjuan
W
Li
Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China.
Ruxing
R
Zhao
Department of Poisoning and Occupational Disease, Qilu Hospital of Shandong University, Jinan 250012, China.
Jidong
J
Liu
Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China.
Meng
M
Tian
Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China.
Yiran
Y
Lu
Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China.
Tianyi
T
He
Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China.
Meng
M
Cheng
Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China.
Kai
K
Liang
Institute of Cell Biology, Shandong University School of Medicine, Jinan 250012, China.
Xia
X
Li
Institute of Cell Biology, Shandong University School of Medicine, Jinan 250012, China.
Xiangdong
X
Wang
Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China.
Yu
Y
Sun
Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China.
Li
L
Chen
D000809:Angiotensins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002470:Cell Survival; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D005786:Gene Expression Regulation; D006085:Graft Survival; D007275:Injections, Intravenous; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D008833:Microcirculation; D055806:Microvessels / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008954:Models, Biological; D018919:Neovascularization, Physiologic; D011169:Portal Vein; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D046509:Tissue Culture Techniques; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D000809:Angiotensins; D007328:Insulin; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat