Type 2 diabetes is caused by dysfunction of pancreatic β cells. Sympathetic neurons innervate pancreatic β cells and noradrenaline inhibits insulin secretion and proliferation of pancreatic β cells in vitro. Previously, we have generated a genetically engineered mice exhibiting inducible and sympathetic neuron-selective loss of the tyrosine hydroxylase gene ( Th-cKO mice), resulting in approximately 70% decline of pancreatic noradrenaline levels. In this study, we investigated the effects of sustained and downregulated sympathetic noradrenergic signaling on the pancreatic β cells using Th-cKO mice. Intraperitoneal glucose tolerance test revealed higher glucose tolerance in Th-cKO mice than the control mice without any difference in insulin tolerance test. Th-cKO mice also exhibited higher circulating insulin levels under glucose challenge. We also found that proliferative activity of pancreatic β cells increased in Th-cKO mice. These results indicate that partial and sustained suppression of sympathetic noradrenaline signaling could enhance insulin secretion and proliferative activity of pancreatic β cells. Additionally, we found that Th-cKO mice showed partial alleviation of streptozotocin-induced hyperglycemia accompanied by increased β cell proliferative response. Our data suggest that sympathetic noradrenaline synthesis can be a potential therapeutic target for diabetes.
Ogawa et al. (Mon,) studied this question.