Cell Rep 2018 Mar 6; 22(10):2667-2676.
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. Cell Rep 2018 Mar 6; 22(10):2667-2676.
Brissova, Marcela; Haliyur, Rachana; Saunders, Diane; Shrestha, Shristi; Dai, Chunhua; Blodgett, David M; Bottino, Rita; Campbell-Thompson, Martha; Aramandla, Radhika; Poffenberger, Gregory; Lindner, Jill; Pan, Fong Cheng; von Herrath, Matthias G; Greiner, Dale L; Shultz, Leonard D.; Sanyoura, May; Philipson, Louis H; Atkinson, Mark; Harlan, David M; Levy, Shawn E; Prasad, Nripesh; Stein, Roland; and Powers, Alvin C, "α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes." (2018). Faculty Research 2018. 55.