Partial Deletion of Perk Improved High-Fat Diet-Induced Glucose Intolerance in Mice

• Published in: Endocrinology and metabolism (Seoul) 2023, 38(6), , pp.782-787
• Main Authors: Lee, Jooyeop, Kim, Min Joo, Moon, Seoil, Lim, Ji Yoon, Park, Kyong Soo, Jung, Hye Seung
• Format: Article
• Language: English
• Subjects: Brief Report; glucose intolerance; high-fat diet; insulin secretion; perk; 내과학
• ISSN: 2093-596X; 2093-5978; 2093-5978
• DOI: 10.3803/EnM.2023.1738

Although pancreatic endoplasmic reticulum kinase (PERK) is indispensable to beta cells, low-dose PERK inhibitor improved glucose- stimulated insulin secretion (GSIS) and hyperglycemia in diabetic mice. Current study examined if partial deletion of Perk (Perk+/-) recapitulated the effects of PERK inhibitor, on the contrary to the complete deletion. Perk+/- mice and wild-type controls were fed with a high-fat diet (HFD) for 23 weeks. Glucose tolerance was evaluated along with serum insulin levels and islet morphology. Perk+/- mice on normal chow were comparable to wild-type mice in various metabolic features. HFD-induced obesity was not influenced by Perk reduction; however, HFD-induced glucose intolerance was significantly improved since 15-week HFD. HFD-induced compromises in GSIS were relieved by Perk reduction, accompanied by reductions in phosphorylated PERK and activating transcription factor 4 (ATF4) in the islets. Meanwhile, HFD-induced islet expansion was not significantly affected. In summary, partial deletion of Perk improved glucose tolerance and GSIS impaired by diet-induced obesity, without changes in body weights or islet mass.