1535-P: Type 2 Diabetes Remission after Roux-en-Y Gastric Bypass Is Related to a Reduction of Pancreatic Noradrenergic Innervation and Beta-Cell Redifferentiation

Background: β cell dedifferentiation has been identified as the process responsible for the functional "disappearance" of β cells from the islets of diabetic subjects.We recently demonstrated that the islets of diabetic subjects are about 3 times more innervated than controls, with a stepwise increase in innervation correlated with worsening glucose tolerance and a direct correlation with the dedifferentiation score. The remission of Type 2 Diabetes after bariatric surgery is well known but the mechanisms which determine it are still on debate. Aim: to test the hypothesis that the anatomical removal of entero-pancreatic innervation induces a reduction of sympathetic innervation with the consequent re-differentiation of β cells, supporting the idea that innervation represents the key mechanism responsible for β cell dedifferentiation. Methods: 10 obese diabetic rat Zucker FA/FA have been fasted overnight for 14 h followed by a glucose tolerance test (GTT) before and 6 weeks after the Roux-en-Y gastric bypass (RYGB) surgery (n=5) or sham (n=5). The morphological analysis of noradrenergic fibers and dedifferentiation score has been performed on the pancreas samples. Results: total glucose level determined by area under the curve (AUC) resulted significantly reduced in the RYGB group compared to sham group (p<0.0001) confirming the remission of type 2 diabetes after bariatric surgery. The number of noradrenergic fibers resulted significantly reduced in RYGB group compared to sham group (p=0.04) as well as the dedifferentiation score (p=0.01). Conclusions: the data confirm that noradrenergic fiber might be directly involved in the process of dedifferentiation. The procedure of RYGB seems to induce a significant reduction of noradrenergic fibers with a consequent reduction of dedifferentiation score, providing a new potential explanation for the remission of type 2 diabetes after bariatric surgery.