Journal article

Inhibition of Y1 receptor signaling improves islet transplant outcome

Kim Loh, Yan-Chuan Shi, Stacey Walters, Mohammed Bensellam, Kailun Lee, Katsuya Dezaki, Masanori Nakata, Chi Kin Ip, Jeng Yie Chan, Esteban N Gurzov, Helen E Thomas, Michaela Waibel, James Cantley, Thomas W Kay, Toshihiko Yada, D Ross Laybutt, Shane T Grey, Herbert Herzog



Failure to secrete sufficient quantities of insulin is a pathological feature of type-1 and type-2 diabetes, and also reduces the success of islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits insulin release in β-cells, and show that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerates the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets. Furthermore, treatment of non-obese diabetic mice with a Y1 receptor antagonist delays the onset of ..

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Awarded by National Health and Medical Research Council (NHMRC) of Australia

Awarded by Grants-in-Aid for Scientific Research

Funding Acknowledgements

This work was supported by the National Health and Medical Research Council (NHMRC) of Australia in the form of a Fellowship #1019734 a project grant #427661 to HH, a project grant #1130222 to STG and a project grant #1080473 to KL. This work received support from the Operational Infrastructure Support Scheme of the Government of Victoria. We thank Sara Litwak, Stacey Fynch, Tom Loudovaris, Felicia Reed, William Stanley, Cameron Kos, and Orvin Atthi for technical assistance.