详细记录  
题名:Central visfatin potentiates glucose-stimulated insulin secretion and beta-cell mass without increasing serum visfatin levels in diabetic rats.
作者:KIM DS; KANG S; MOON NR; PARK S;
来源:Cytokine. 2013 Dec 11. pii: S1043-4666(13)00758-8. doi: [ IF= 2.52 ] ]
URL :10.1016/j.cyto.2013.11.008
日期:20140102
摘要:INTRODUCTION: Our previous study revealed that plasma visfatin levels were lower
in pregnant women with gestational diabetes (GDM) than non-GDM independent of
prepreganacy BMI. We examined whether central visfatin modulates energy and
glucose homeostasis via altering insulin resistance, insulin secretion or islet
morphometry in diabetic rats. METHODS: Partial pancreatectomized, type 2
diabetic, rats were interacerbroventricularly infused with visfatin
(100ng/rat/day, Px-VIS), visfatin+visfatin antagonist, CHS-828 (100mug/rat/day,
Px-VIS-ANT), or saline (control, Px-Saline) via osmotic pump, respectively, for
4weeks. RESULTS: Central visfatin improved insulin signaling (pAkt-->pFOXO-1) but
not pSTAT3 in the hypothalamus. Central visfatin did not alter serum visfatin
levels in diabetic rats whereas the levels were higher in non-diabetic rats than
diabetic rats. Body weight at the 2nd week was lowered in the Px-VIS group due to
decreased food intake in the first two weeks compared to the Px-Saline group and
energy expenditure was not significantly different among the treatment groups of
diabetic rats. Visfatin antagonist treatment nullified the central visfatin
effect. Px-VIS increased whole body glucose disposal rates in euglycemic
hyperinsulinemic clamp compared to Px-Saline and lowered hepatic glucose output,
whereas Px-VIS-ANT blocked the visfatin effect on insulin resistance (P<0.05). In
hyperglycemic clamp study, the area under the curve of insulin in first and
second phase were significantly higher in the Px-VIS group than the Px-Saline
group without modifying insulin sensitivity at the hyperglycemic state, whereas
the increase in serum insulin levels was blocked in the Px-VIS-ANT group. Central
visfatin also increased beta-cell mass by increasing beta-cell proliferation.
CONCLUSIONS: Central visfatin improved glucose homeostasis by increasing insulin
secretion and insulin sensitivity at euglycemia through the hypothalamus in
diabetic rats. Therefore, visfatin is a positive modulator of glucose homeostasis
by delivering the hypothalamic signals into the peripheries.

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