title: Loss of mPer2 increases plasma insulin levels by enhanced glucose-stimulated insulin secretion and impaired insulin clearance in mice.
abstract: The existence of peripheral oscillators has been shown, and they are critically important for organizing the metabolism of the whole body. Here we show that mice deficient in mPer2 markedly increase circulatory levels of insulin compared with wild type mice. Insulin secretion was more effectively stimulated by glucose, and alloxan, a glucose analogue, induced more severe hyperglycemia in mPer2-deficient mice. Hepatic insulin degrading enzyme (Ide) displayed an obvious day and night rhythm, which was impaired in mPer2-deficient mice, leading to a decrease in insulin clearance. Deficiency in mPer2 caused increased Clock expression and decreased expression of Mkp1 and Ide1, possibly underlying the observed phenotypes and suggesting that mPer2 plays a role in regulation of circulating insulin levels.
authors.affiliation: Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mengyi
authors.initials: M
authors.lastname: Zhou
authors.forename: Shiming
authors.initials: S
authors.lastname: Wang
authors.forename: Zichun
authors.initials: Z
authors.lastname: Hua
authors.forename: Jianfa
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000096:biosynthesis / Q000494:pharmacology*; D051273:Glucose Transporter Type 2 / Q000235:genetics; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000097:blood* / Q000378:metabolism*; D000078790:Insulin Secretion; D007339:Insulysin / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D056950:Period Circadian Proteins / Q000172:deficiency*
chemical_list: D051273:Glucose Transporter Type 2; D007328:Insulin; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D006003:Glycogen; D007339:Insulysin; D005947:Glucose