Senp2 expression was induced by chronic glucose stimulation in INS1 cells, and it was required for the associated induction of Ccnd1 and Mafa

Abstract

Post-translational modification by bonding of small ubiquitin-like modifier (SUMO) peptides influences various cellular functions, and is regulated by SUMO-specific proteases (SENPs). Several proteins have been suggested to have diverse impact on insulin synthesis and secretion through SUMO modification in β cells. However, the role of SUMO modification in β cell mass has not been established. Here, we examined the changes in expression of Senp in INS1 cells and pancreatic islets under diabetes-relevant stress conditions and associated changes in β cell mass. Treatment with 25 mM glucose for 72 h induced Senp2 mRNA expression but not that of Senp1 in INS1 cells. Immunohistochemical staining with anti-SENP2 antibody on human pancreas sections revealed that SENP2 was localized in the nucleus. Moreover, in a patient with type 2 diabetes, SENP2 levels were enhanced, especially in the cytoplasm. Senp2 cytoplasmic levels were also increased in islet cells in obese diabetic mice. Cell number peaked earlier in INS1 cells cultured in high-glucose conditions compared to those cultured in control media. This finding was associated with increased Ccnd1 mRNA expression in high-glucose conditions, and siRNA-mediated Senp2 suppression abrogated it. Mafa expression, unlike Pdx1, was also dependent on Senp2 expression during high-glucose conditions. In conclusion, Senp2 may play a role in β cell mass in response to chronic high-glucose through Cyclin D1 and Mafa.

Effects of dietary carbohydrate sources on lipid metabolism and SUMOylation modification in the liver tissues of yellow catfish

“…Our study indicated that senp2 and senp3 mRNA levels were lower for yellow catfish fed the glucose than those fed the dextrin. In contrast, Jung et al (40) found that the expression of Senp2, but not Senp1, was triggered by chronic high-glucose stimulation in insulin-producing cells. Moreover, Jung et al (40) pointed out that the induction of different SENP needed different stimulations according to cell types.…”

“…In contrast, Jung et al (40) found that the expression of Senp2, but not Senp1, was triggered by chronic high-glucose stimulation in insulin-producing cells. Moreover, Jung et al (40) pointed out that the induction of different SENP needed different stimulations according to cell types. In response to glucose, the expression of SENP2 was predominant in the cytoplasm than in the nucleus (40) .…”

“…Moreover, Jung et al (40) pointed out that the induction of different SENP needed different stimulations according to cell types. In response to glucose, the expression of SENP2 was predominant in the cytoplasm than in the nucleus (40) . Obviously, the physiological importance of the senp in SUMOylation needs to be clarified, and further studies were needed to elucidate the molecular mechanism of the senp transcriptional repression by glucose.…”

Identification of 10 SUMOylation-Related Genes From Yellow Catfish Pelteobagrus fulvidraco, and Their Transcriptional Responses to Carbohydrate Addition in vivo and in vitro

“…In mammals, several studies indicated that SUMOylation modification of proteins were influenced by carbohydrate (or glucose) levels ( Huang et al, 2013 ; Jung et al, 2016 ), but no such studies were conducted in fish. For the first time, our study explored the effects of dietary carbohydrate levels on mRNA expressions of the 10 genes in four tissues in fish, and detected the effect of glucose incubation on mRNA expressions of SUMOylation related genes in primary hepatocytes from yellow catfish.…”

“…Similarly, Huang et al (2013) reported that high glucose increased the expression of sumo1 and sumo2/3 in glomerular mesangial cells of the rats. Jung et al (2016) pointed out that different stimulations were required for inducing different SENPs according to cell types, and concluded that chronic high glucose was responsible for inducing Senp2 expression in insulin-producing cells.…”