Functional loss of pancreatic islets in type 2 diabetes: How can we halt it?

The loss of beta-cell functional mass is a necessary and early condition in the development of type 2 diabetes (T2D). In T2D patients, beta-cell function is already reduced by about 50% at diagnosis and further declines thereafter. Beta-cell mass is also reduced in subjects with T2D, and islets from diabetic donors are smaller compared to non-diabetic donors. Thus, beta-cell regeneration and/or preservation of the functional islet integrity should be highly considered for T2D treatment and possibly cure. To date, the available anti-diabetes drugs have been developed as "symptomatic" medications since they act to primarily reduce elevated blood glucose levels. However, a truly efficient anti-diabetes medication, capable to prevent the onset and progression of T2D, should stop beta-cell loss and/or promote the restoration of fully functional beta-cell mass, independently of reducing hyperglycemia and ameliorating glucotoxicity on the pancreatic islets. This review provides a view of the experimental and clinical evidence on the ability of available anti-diabetes drugs to exert protective effects on beta-cells, with a specific focus on human pancreatic islets and clinical trials. Potential explanations for the lack of concordance between evidence of beta-cell protection in vitro and of persistent amelioration of beta-cell function in vivo are also discussed.

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest A.N., N.M., G.B., A.C., and S.P. declare no competing interests. For L.L.: Advisory Boards: AstraZeneca, Eli Lilly, Novo Nordisk, Roche Diabetes Care, Sanofi. For F.G.: Advisory Boards: AstraZeneca, Eli Lilly, Novo Nordisk, Roche Diabetes Care; Consultant: Boehringer Ingelheim, Lifescan, Merck Sharp & Dohme, Sanofi, AstraZeneca, Medimmune, Roche Diabetes Care; Research Support: Eli Lilly; Lifescan, Takeda.