Assessment of Islet Alpha- and Beta-Cell Function

Abstract

Abnormal secretion of insulin and glucagon are key hormonal defects in the pathogenesis of diabetes. Type 1 diabetes is characterized by severely impaired β-cell function; glucagon secretion in response to hypoglycemia becomes impaired over time. In type 2 diabetes, hyperglycemia results from impaired insulin secretion allied to inappropriate glucagon secretion. Analysis of islet α- and β-cell function is required to understand the pathophysiology of diabetes and the mechanisms of action of pharmacotherapies. Assessing the integrity of the incretin axis and α- and β-cell function has come to prominence with the development of the dipeptidyl peptidase (DPP-4) inhibitors and glucagon-like peptide (GLP)-1 receptor agonists, as well as glucagon receptor antagonists. The range of techniques for the clinical assessment of insulin secretion and response to therapeutic interventions reflects the absence of a gold standard reference method. Since no single method adequately captures all potentially relevant aspects of α- and β-cell function several methods may be required to inform drug development decisions.