title: 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.
authors.affiliation: a Department of Internal Medicine , Seoul National University College of Medicine , Seoul , Republic of Korea.|b Innovative Research Institute for Cell Therapy , Seoul , Republic of Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Jung
authors.affiliation: b Innovative Research Institute for Cell Therapy , Seoul , Republic of Korea.
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Kang
authors.affiliation: a Department of Internal Medicine , Seoul National University College of Medicine , Seoul , Republic of Korea.
authors.forename: Ho Seon
authors.initials: HS
authors.lastname: Park
authors.affiliation: a Department of Internal Medicine , Seoul National University College of Medicine , Seoul , Republic of Korea.
authors.forename: Byung Yong
authors.initials: BY
authors.lastname: Ahn
authors.affiliation: b Innovative Research Institute for Cell Therapy , Seoul , Republic of Korea.
authors.forename: Hakmo
authors.initials: H
authors.lastname: Lee
authors.affiliation: a Department of Internal Medicine , Seoul National University College of Medicine , Seoul , Republic of Korea.
authors.forename: Min Joo
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: c Department of Surgery , Seoul National University College of Medicine , Seoul , Republic of Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Jang
authors.affiliation: c Department of Surgery , Seoul National University College of Medicine , Seoul , Republic of Korea.
authors.forename: Sun-Whe
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002460:Cell Line; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged
chemical_list: C485159:MAFA protein, human; D051473:Maf Transcription Factors, Large; D019938:Cyclin D1; D003546:Cysteine Endopeptidases; C501833:SENP2 protein, human; D005947:Glucose
keywords: SENP2; cell mass; diabetes; hyperglycemia; pancreatic islets