| Autor: |
Chun-Xia Yi, Kristy M Heppner, Henriette Kirchner, Jenny Tong, Maximillian Bielohuby, Bruce D Gaylinn, Timo D Müller, Erin Bartley, Harold W Davis, Yongmei Zhao, Anupama Joseph, Traci Kruthaupt, Nickki Ottaway, Dhiraj Kabra, Kirk M Habegger, Stephen C Benoit, Martin Bidlingmaier, Michael O Thorner, Diego Perez-Tilve, Matthias H Tschöp, Paul T Pfluger |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Předmět: |
|
| Zdroj: |
PLoS ONE, Vol 7, Iss 2, p e32100 (2012) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0032100 |
| Popis: |
OBJECTIVE: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. METHODOLOGY: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. PRINCIPAL FINDINGS: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. CONCLUSION:The endogenous GOAT-ghrelin-GHSR system is not essential for the maintenance of euglycemia during prolonged calorie restriction. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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