Sources of beta cells inside the pancreas

Abstract

The generation of beta(-like) cells to compensate for their absolute or relative shortage in type 1 and type 2 diabetes is an obvious therapeutic strategy. Patients first received grafts of donor islet cells over 25 years ago, but this procedure has not become routine in clinical practice because of a donor cell shortage and (auto)immune problems. Transplantation of differentiated embryonic and induced pluripotent stem cells may overcome some but not all the current limitations. Reprogramming exocrine cells towards functional beta(-like) cells would offer an alternative abundant and autologous source of beta(-like) cells. This review focuses on work by our research group towards achieving such a source of cells. It summarises a presentation given at the 'Can we make a better beta cell?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Amin Ardestani and Kathrin Maedler, DOI: 10.1007/s00125-016-3892-9 , and by Heiko Lickert and colleagues, DOI: 10.1007/s00125-016-3949-9 ) and a commentary by the Session Chair, Shanta Persaud (DOI: 10.1007/s00125-016-3870-2 ).

Effect of moderate and high intensity chronic exercise on the pancreatic islet morphometry in healthy rats: BDNF receptor participation

“…In humans is about 50-60% while in rodents reaches 80%, 4 therefore, alterations of b-cells directly affect the islet area. Mechanisms such as b-cell neogenesis (differentiation from precursor cells), b-cell proliferation and transdiferentiation, and b-cell hypertrophy are responsible for b-cell mass increase; 5,6,7,8,9 while, b-cell reduction is determined by apoptosis and b-cell atrophy. 5,7 Studies in obese or diabetic rodent models have shown that exercise counter-regulates the IRS2-PI3K-pAkt growth pathway attenuated in Langerhans islet resulting in a bigger b cell area, major b cell proliferation rate and lower apoptosis.…”

Can we make a better beta cell?

“…Harry Heimberg [6] considered the sources of beta cells available within the pancreas, with emphasis on the benefits of reprogramming the abundant populations of exocrine cells into fully functional beta cells. He summarised data from his group using the partial duct ligation (PDL) and growth factor therapy models to define the conditions necessary for exocrine to beta cell reprogramming.…”