Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lep ob/ob mice.
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.
Sekiya
Motohiro
M
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Yahagi
Naoya
N
Tamura
Yoshiaki
Y
Okazaki
Hiroaki
H
Igarashi
Masaki
M
Ohta
Keisuke
K
Takanashi
Mikio
M
Kumagai
Masayoshi
M
Takase
Satoru
S
Nishi
Makiko
M
Takeuchi
Yoshinori
Y
Izumida
Yoshihiko
Y
Kubota
Midori
M
Ohashi
Ken
K
Iizuka
Yoko
Y
Yagyu
Hiroaki
H
Gotoda
Takanari
T
Nagai
Ryozo
R
Shimano
Hitoshi
H
Yamada
Nobuhiro
N
Kadowaki
Takashi
T
Ishibashi
Shun
S
Osuga
Jun-ichi
J
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
D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D002787:Sterol Esterase