title: Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lep ob/ob mice.
abstract: It has long been a matter of debate whether the hormone-sensitive lipase (HSL)-mediated lipolysis in pancreatic beta-cells can affect insulin secretion through the alteration of lipotoxicity. We generated mice lacking both leptin and HSL Lep(ob/ob)/HSL(-/-) and explored the role of HSL in pancreatic beta-cells in the setting of obesity. Lep(ob/ob)/HSL(-/-) developed elevated blood glucose levels and reduced plasma insulin levels compared with Lep(ob/ob)/HSL(+/+) in a fed state, while the deficiency of HSL did not affect glucose homeostasis in Lep(+/+) background. The deficiency of HSL exacerbated the accumulation of triglycerides in Lep(ob/ob) islets, leading to reduced glucose-stimulated insulin secretion. The deficiency of HSL also diminished the islet mass in Lep(ob/ob) mice due to decreased cell proliferation. In conclusion, HSL affects insulin secretary capacity especially in the setting of obesity.
authors.affiliation: Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Sekiya
authors.forename: Naoya
authors.initials: N
authors.lastname: Yahagi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okazaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Igarashi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ohta
authors.forename: Mikio
authors.initials: M
authors.lastname: Takanashi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kumagai
authors.forename: Satoru
authors.initials: S
authors.lastname: Takase
authors.forename: Makiko
authors.initials: M
authors.lastname: Nishi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Izumida
authors.forename: Midori
authors.initials: M
authors.lastname: Kubota
authors.forename: Ken
authors.initials: K
authors.lastname: Ohashi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Iizuka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yagyu
authors.forename: Takanari
authors.initials: T
authors.lastname: Gotoda
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Osuga
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D049109:Cell Proliferation; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000201:enzymology*; D002787:Sterol Esterase / Q000172:deficiency* / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D002787:Sterol Esterase