Possibility of adiponectin use to improve islet transplantation outcomes

Naoaki Sakata,Shohta Kodama,Kiyoshi Chinen,Ryo Kawakami,Gumpei Yoshimatsu

doi:10.1038/s41598-021-04245-0

Naoaki Sakata, Shohta Kodama + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-04245-0

Copy DOI

Abstract

Although islet transplantation (ITx) is a promising therapy for severe diabetes mellitus, further advancements are necessary. Adiponectin, an adipokine that regulates lipid and glucose metabolism, exerts favorable effects on islets, such as reinforcement of the insulin-releasing function. This study evaluated the possibility of adiponectin use to improve ITx outcomes. We treated mouse islets with 10 µg/mL recombinant mouse adiponectin by overnight culture and then assessed the insulin-releasing, angiogenic, and adhesion functions of the islets. Furthermore, 80 syngeneic islet equivalents with or without adiponectin treatment were transplanted into the renal subcapsular space of diabetic mice. In in vitro assessment, released insulin at high glucose stimulation, insulin content, and expressions of vascular endothelial growth factor and integrin β1 were improved in adiponectin-treated islets. Furthermore, adiponectin treatment improved the therapeutic effect of ITx on blood glucose levels and promoted angiogenesis of the transplanted islets. However, the therapeutic effect was not pronounced in glucose tolerance test results. In conclusion, adiponectin treatment had preferable effects in the insulin-releasing, angiogenic, and adhesion functions of islets and contributed to the improvement of ITx. The future use of adiponectin treatment in clinical settings to improve ITx outcomes should be investigated.

Highlights

Yamauchi et al revealed that adiponectin deficiency caused insulin resistance with glucose intolerance using genetically modified animals[9,17]
They clarified that adiponectin activated 5′ AMP-activated protein kinase (AMPK) via AdipoR1 on skeletal muscle and improved glucose uptake, reduced gluconeogenesis, and increased insulin sensitivity in the tissue[18,19]
Adiponectin directly affects pancreatic islets, exerting an antiapoptotic effect and improving the insulin-releasing function. Regarding the former, Jian et al revealed that β-cell apoptosis induced by streptozotocin administration and a high-fat diet was attenuated in mice with adiponectin overexpression by preventing the cleavage of caspase 8, 9, and 3 12

Summary

Introduction

The glucose-stimulated insulin secretion (GSIS) data revealed that the level of insulin released under conditions of high glucose stimulation was significantly higher in islets in the adiponectin (+) group (104.97 ± 7.45 vs 73.96 ± 6.31 pg/islet × h, p = 0.016; Fig. 2A). There was no difference in the amount of insulin released under conditions of low glucose stimulation between the two groups (37.63 ± 2.86 vs 36.55 ± 1.80 pg/islet × h; Fig. 2A).

Results

Conclusion