α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes

Marcela Brissova; Rachana Haliyur; Diane Saunders; Shristi Shrestha; Chunhua Dai; David M. Blodgett; Rita Bottino; Martha Campbell-Thompson; Radhika Aramandla; Gregory Poffenberger; Jill Lindner; Fong Cheng Pan; Matthias G. von Herrath; Dale L. Greiner; Leonard D. Shultz; May Sanyoura; Louis H. Philipson; Mark Atkinson; David M. Harlan; Shawn E. Levy; Nripesh Prasad; Roland Stein; Alvin C. Powers

α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes

2018

Summary: Many patients with type 1 diabetes (T1D) have residual β cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual β cells and α cells in the islet endocrine compartment are largely unknown, due to the difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant β cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D α cells was markedly reduced, and these cells had alterations in transcription factors constituting α and β cell identity. In the native pancreas and after placing the T1D islets into a non-autoimmune, normoglycemic in vivo environment, there was no evidence of α-to-β cell conversion. These results suggest an explanation for the disordered T1D counterregulatory glucagon response to hypoglycemia. : Brissova et al. find that β cells in the type 1 diabetic (T1D) pancreas maintain several functional and molecular features, but α cells have impaired glucagon secretion and an altered gene expression profile. These findings provide insight into the mechanism of α cell dysfunction in T1D. Keywords: type 1 diabetes, glucagon, insulin, pancreatic islet, alpha cells, human

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