Recombinant Reg3α Prevents Islet ß-Cell Apoptosis and Promotes ß-Cell Regeneration.

Progressive loss and dysfunction of islet ß-cells has not yet been solved in the treatment of diabetes. Regenerating protein (Reg) has been identified as a trophic factor which is demonstrated to be associated with pancreatic tissue regeneration. We previously produced recombinant Reg3α protein (rReg3α) and proved that it protects against acute pancreatitis in mice. Whether rReg3α protects islet ß-cells in diabetes has been elusive. In the present study, rReg3α stimulated MIN6 cell proliferation and resisted STZ-caused cell death. The protective effect of rReg3α was also found in mouse primary islets. In BALB/c mice, rReg3α administration largely alleviated STZ-induced diabetes by the preservation of ß-cell mass. The protective mechanism could be attributed to Akt/Bcl-2/-xL activation and GRP78 upregulation. Scattered insulin-expressing cells and clusters with small size, low insulin density, and exocrine distribution were observed and considered to be neogenic. In isolated acinar cells with wheat germ agglutinin (WGA) labeling, rReg3α treatment generated insulin-producing cells through Stat3/Ngn3 signaling, but these cells were not fully functional in response to glucose stimulation. Our results demonstrated that rReg3α resists STZ-induced ß-cell death and promotes ß-cell regeneration. rReg3α could serve as a potential drug for ß-cell maintenance in anti-diabetic treatment.

Endothelial dysfunction in diabetes and hypertension: Role of microRNAs and long non-coding RNAs.

The vascular endothelium acts as a barrier between the blood flow and the inner lining of the vessel wall, and it functions as a filtering machinery to filter out any unwanted transfer of materials from both sides (i.e. the blood and the surrounding tissues). It is evident that diseases such as diabetes, obesity, and hypertension disturb the normal endothelial functions in humans and lead to endothelial dysfunction, which may further precede to the development of atherosclerosis. Long non-coding RNAs and micro RNAs both are types of non-coding RNAs which, in the recent years, have increasingly been studied in the pathophysiology of many diseases including diabetes, obesity, cardiovascular diseases, neurological diseases, and others. Recent findings have pointed out important aspects on their relevance to endothelial function as well as dysfunction of the system which may arise from presence of diseases such as diabetes and hypertension. Diabetes or hypertension-mediated endothelial dysfunction show characteristics such as reduced nitric oxide synthesis through suppression of endothelial nitric oxide synthase activity in endothelial cells, reduced sensitivity of nitric oxide in smooth muscle cells, and inflammation - all of which have been either shown to be directly caused by gene regulatory mechanisms of non-coding RNAs or shown to be having a correlation with them. In this review, we aim to discuss such findings on the role of these non-coding RNAs in diabetes or hypertension-associated endothelial dysfunction and the related mechanisms that may pave the way for alleviating endothelial dysfunction and its related complications such as atherosclerosis.