Supporting networking and collaborative research among early career scientists and clinicians.

Activating islet NAMPT to improve islet transplant outcomes

Daniel Egbase, King's College London



Islet transplantation is promising treatment strategy for type 1 diabetes (T1D), which has the potential to reduce or eliminate requirement for endogenous insulin therapy. Consequently, islet transplantation can reduce risk of acute-complications of insulin therapy, (e.g. hypoglycaemia), and improve long-term glycaemic control, reducing onset of diabetic complications1. However, graft failure, particularly immediately after transplantation, limits long-term success of this treatment, and identifying novel strategies to improve graft survival is essential1.

Our preliminary studies show that activation of NAMPT, a key enzyme for NAD biosynthesis2, with SBI-7978123, protects against inflammation-mediated death and dysfunction in isolated mouse and human pancreatic islets. Moreover, NAMPT activation can reverse inflammation-mediated increases in expression of genes associated with islet allograft rejection, and islet apoptosis and inflammation. We hypothesise that NAMPT activation can improve transplanted graft survival.

To examine whether NAMPT activation can improve:

(a) function,

(b) survival

of mouse islets transplanted into diabetic mice.

This project will determine whether NAMPT activation can improve islet graft survival and function in pre-clinical T1D models, generating proof-of-concept data to support development of NAMPT activators for improvement of islet transplantation in T1D.

1)Shapiro et al, Nature reviews Endocrinology,13:268-277(2017)

2)Imai S. Current pharmaceutical design 15:20-28(2009)

3)Gardell et al, Nature Communications,10,3241(2019)


Grant awarded: £4,800.00

© The Bioscientifica Trust.
All rights reserved. | Privacy Policy