Role of adenosine signalling and metabolism in β-cell regeneration

Glucose homeostasis, which is controlled by the endocrine cells of the pancreas, is disrupted in both type I and type II diabetes. Deficiency in the number of insulin-producing beta cells - a primary cause of type I diabetes and a secondary contributor of type II diabetes - leads to hyperglycemia and hence an increase in the need for insulin. Although diabetes can be controlled with insulin injections, a curative approach is needed. A potential approach to curing diabetes involves regenerating the beta-cell mass, e.g. by increasing beta-cell proliferation, survival, neogenesis or transdifferentiation. The nucleoside adenosine and its cognate nucleotide ATP have long been known to affect insulin secretion, but have more recently been shown to increase beta-cell proliferation during homeostatic control and regeneration of the beta-cell mass. Adenosine is also known to have anti-inflammatory properties, and agonism of adenosine receptors can promote the survival of beta-cells in an inflammatory microenvironment. In this review, both intracellular and extracellular mechanisms of adenosine and ATP are discussed in terms of their established and putative effects on beta-cell regeneration. (C) 2013 Elsevier Inc. All rights reserved.