Reflections on the state of diabetes research and prospects for treatment

Abstract

Research on the etiology and treatment of diabetes has made substantial progress. As a result, several new classes of antidiabetic drugs have been introduced in clinical practice. Nonetheless, the number of patients achieving glycemic control targets has not increased for the past 20 years. Two areas of unmet medical need are the restoration of insulin sensitivity and the reversal of pancreatic beta cell failure. In this review, we integrate research advances in transcriptional regulation of insulin action and pathophysiology of beta cell dedifferentiation with their potential impact on prospects of a durable "cure" for patients suffering from type 2 diabetes.

Cyb5r3 activation rescues secondary failure to sulfonylurea but not β-cell dedifferentiation

“…In this study, we report that six-week GLB treatment induces β-cell dedifferentiation in a manner that is further enhanced by Cyb5r3 ablation, and that a Cyb5r3 activator restores insulin secretion but not expression of β-cell dedifferentiation markers. The data are consistent with the notion that the three steps identified in our overarching scheme of β-cell failure, decreased insulin secretion, metabolic inflexibility, and dedifferentiation [12] are mechanistically distinct and likely to respond to different treatment agents [23,24]. β-cell dedifferentiation is the terminal stage of β-cell failure.…”

“…In conclusion, we show that chronic SU administration accelerates progression of β-cell dedifferentiation and that a Cyb5r3 activator improves insulin secretion caused by SU secondary failure without reversing β-cell dedifferentiation. These results are consistent with the view that diabetes treatment should be tailored to different phases of progression of the disease [24] and can lead to novel pharmacological approaches to preserve β-cell function and prevent diabetes progression.…”