Rgs16 is a marker of islet expansion in diabetes

In diabetes, pancreatic beta cells replicate to meet the increased demand for insulin. However, there is no established therapy specifically stimulating islet neogenesis. Regulators of G‐protein Signaling (RGS) proteins are feedback inhibitors of G‐protein Coupled Receptor (GPCR) signaling. RGS gene expression can be induced by the agonists they feedback regulate, and thereby serve as indicator of GPCR signaling in vivo . We characterized Rgs16::GFP reporter gene that is activated in a subset of beta cells in adult Type1 (T1) and Type2 (T2) diabetic mice. The intensity of GFP expression in pancreatic micrographs was quantified using ImageJ. In T1 and T2 diabetic mice, Rgs16::GFP emerged within two weeks of persistent hyperglycemia and expanded thereafter in more islets and beta cells. Continuous hyperglycemia was required for Rgs16::GFP expression. In the T1 diabetes mouse model of recovery from beta cell death (PANIC‐ATTAC), Rgs16::GFP expression was not observed in islets of mice that had recovered normal glycemia, whereas it remained high in age‐matched hyperglycemic mice. Rgs16::GFP expression could also be initiated rapidly in the streptozotocin (STZ) induced T1 diabetes model. Furthermore, daily insulin injections of STZ treated mice transiently lowered blood glucose and suppressed Rgs16::GFP expression. In summary, Rgs16 is a reliable and early marker of signals that stimulate adult islet expansion in both T1 and T2 diabetes. We will determine if Rgs16 regulates GPCR‐dependent islet expansion provoked by chronic hyperglycemia. Funding: NIH ( GM061395 ) to TM Wilkie.