The GOAT-ghrelin system is not essential for hypoglycemia prevention during prolonged calorie restriction.
The GOAT-ghrelin system is not essential for hypoglycemia prevention during prolonged calorie restriction.
复制标题
DOI：
10.1371/journal.pone.0032100
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Pfluger PT
中科院分区：
文献类型：
--
作者：
Yi CX;Heppner KM;Kirchner H;Tong J;Bielohuby M;Gaylinn BD;Müller TD;Bartley E;Davis HW;Zhao Y;Joseph A;Kruthaupt T;Ottaway N;Kabra D;Habegger KM;Benoit SC;Bidlingmaier M;Thorner MO;Perez-Tilve D;Tschöp MH;Pfluger PT
Ghrelin O-酰基转移酶(Ghrelin O-acylTransfer ase，山羊)的Ghrelin酰化对于预防长期负能量平衡状态下的低血糖是必不可少的。利用一套独特的山羊/ghrelin/生长激素促分泌素受体(GHSR)系统的四种不同的遗传功能丧失模型，我们彻底检验了缺乏ghrelin激活或信号将导致卡路里缺乏时低血糖的假设。雄性和雌性Ghrelin基因敲除(KO)小鼠对山羊、Ghrelin、GHSR或同时使用Ghrelin和GHSR(DKO)的小鼠进行长时间的热量限制(占自由饮食摄入量的40%)。每天记录体重、脂肪质量和血糖水平，并与野生型(WT)对照组进行比较。当达到2%或更少的体脂质量时，为每只小鼠生成48小时的血糖曲线。采集血液样本，分析血液中酰基和去脂基-生长激素、胰岛素样生长因子-1和胰岛素的循环水平。慢性卡路里限制会逐渐降低所有小鼠的体重和体脂质量，而不考虑基因。当脂肪质量连续两天消耗到体重的2%或更少时，所有基因型的一些小鼠都会发生随机的低血糖事件。在包括山羊KO小鼠在内的四种Ghrelin信号失活模型中的任何一种中，低血糖发生率都没有增加。此外，没有观察到胰岛素或IGF-1水平在不同基因型之间的差异。内源性山羊-Ghrelin-GHSR系统不是在长期热量限制期间维持正常血糖所必需的。
Ghrelin acylation by ghrelin O-acyltransferase (GOAT) has recently been reported to be essential for the prevention of hypoglycemia during prolonged negative energy balance. Using a unique set of four different genetic loss-of-function models for the GOAT/ghrelin/growth hormone secretagogue receptor (GHSR) system, we thoroughly tested the hypothesis that lack-of-ghrelin activation or signaling would lead to hypoglycemia during caloric deprivation. Male and female knockout (KO) mice for GOAT, ghrelin, GHSR, or both ghrelin and GHSR (dKO) were subjected to prolonged calorie restriction (40% of ad libitum chow intake). Body weight, fat mass, and glucose levels were recorded daily and compared to wildtype (WT) controls. Forty-eight hour blood glucose profiles were generated for each individual mouse when 2% or less body fat mass was reached. Blood samples were obtained for analysis of circulating levels of acyl- and desacyl-ghrelin, IGF-1, and insulin. Chronic calorie restriction progressively decreased body weight and body fat mass in all mice regardless of genotype. When fat mass was depleted to 2% or less of body weight for 2 consecutive days, random hypoglycemic events occurred in some mice across all genotypes. There was no increase in the incidence of hypoglycemia in any of the four loss-of-function models for ghrelin signaling including GOAT KO mice. Furthermore, no differences in insulin or IGF-1 levels were observed between genotypes. The endogenous GOAT-ghrelin-GHSR system is not essential for the maintenance of euglycemia during prolonged calorie restriction.
登录
查看更多内容
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3.7
作者：
Ma X;Lin L;Qin G;Lu X;Fiorotto M;Dixit VD;Sun Y
通讯作者：
Sun Y
影响因子：
4.1
作者：
Gauna, Carlotta;Delhanty, Patric J. D.;van der Lely, Aart Jan
通讯作者：
van der Lely, Aart Jan
影响因子：
5.8
作者：
Broglio, F;Gottero, C;Ghigo, E
通讯作者：
Ghigo, E
DOI：
10.1073/pnas.0800708105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Gutierrez, Jesus A.;Solenberg, Patricia J.;Hale, John E.
通讯作者：
Hale, John E.