Loss of Deaf1 function leads to reduced peripheral tissue antigen expression in lymph node stromal cells and may contribute to a breakdown in peripheral tolerance, while reduced Adora1 function results in an early intrinsic alpha cell defect that may explain the hyperglucagonemia and resulting beta cell stress observed prior to the onset of diabetes.
Expression of the spliced variant (Adora1-Var) was upregulated in the pancreas of 12-week-old NOD versus age-matched NOD.B10 (non-diabetes-susceptible) control mice and was detected in the pancreas of AA(+) patients but not in control subjects or overtly diabetic patients, suggesting that inflammation drives the splicing of Adora1.
This hypothesis has recently been questioned due to the observation that adenosine A(1)-receptor knockout mice, previously shown to lack a functional TGF mechanism, still display a pronounced hyperfiltration when diabetes is induced.