Α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes.

Many patients with type 1 diabetes (T1D) have residual beta 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 b cells and a 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 b cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D a cells was markedly reduced, and these cells had alterations in transcription factors constituting a and beta 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 alpha-to-beta cell conversion. These results suggest an explanation for the disordered T1D counterregulatory glucagon response to hypoglycemia.