The GOAT-ghrelin system is not essential for hypoglycemia prevention during prolonged calorie restriction
| Autor: | Kristy M. Heppner, Henriette Kirchner, Erin Bartley, Yongmei Zhao, Diego Perez-Tilve, Michael O. Thorner, Nickki Ottaway, Traci Kruthaupt, Maximillian Bielohuby, Bruce D. Gaylinn, Anupama Joseph, Harold W. Davis, Timo D. Müller, Dhiraj G. Kabra, Matthias H. Tschöp, Paul T. Pfluger, Kirk M. Habegger, Jenny Tong, Chun-Xia Yi, Martin Bidlingmaier, Stephen C. Benoit |
|---|---|
| Přispěvatelé: | Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Blood Glucose
Male Anatomy and Physiology medicine.medical_treatment Growth hormone secretagogue receptor Glycobiology lcsh:Medicine Adipose tissue Endogeny Biochemistry Mice Insulin Insulin-Like Growth Factor I lcsh:Science Adiposity Mice Knockout Multidisciplinary digestive oral and skin physiology Ghrelin Models Animal Medicine Female hormones hormone substitutes and hormone antagonists Research Article medicine.medical_specialty Genotype Animal Types Calorie restriction Blood sugar Endocrine System Hypoglycemia Biology Internal medicine medicine Animals Caloric Restriction Endocrine Physiology Body Weight lcsh:R Membrane Proteins medicine.disease Metabolism Endocrinology Veterinary Science lcsh:Q Physiological Processes Acyltransferases |
| Zdroj: | PLoS ONE 7:e32100 (2012) PLoS ONE, Vol 7, Iss 2, p e32100 (2012) PLoS ONE PLoS ONE, 7(2). Public Library of Science |
| DOI: | 10.5282/ubm/epub.15329 |
| 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: | OpenAIRE |
| Externí odkaz: |
|