Obesity in MENX rats is accompanied by high circulating levels of ghrelin and improved insulin sensitivity.
Diabetes 65, 406-420 (2015)
Ghrelin, the natural ligand of the growth hormone secretagogue receptor (GHS-R1a), is mainly secreted from the stomach and regulates food intake and energy homeostasis. p27 regulates cell cycle progression in many cell types. Here, we report that rats affected by the multiple endocrine neoplasia syndrome MENX, caused by a p27 mutation, develop pancreatic islet hyperplasia containing elevated numbers of ghrelin-producing epsilon cells. The metabolic phenotype of MENX-affected rats featured high endogenous acylated and unacylated plasma ghrelin levels. Supporting increased ghrelin action, MENX rats show increased food intake, enhanced body fat mass, and elevated plasma levels of triglycerides and cholesterol. Ghrelin effect on food intake was confirmed by treating MENX rats with a GHS-R1a antagonist. At 7,5 months, MENX-affected rats show decreased mRNA levels of hypothalamic GHS-R1a, neuropeptide Y (NPY), and agouti-related protein (AgRP), suggesting that prolonged hyperghrelinemia may lead to decreased ghrelin efficacy. In line with ghrelin's proposed role in glucose metabolism, we find decreased glucose-stimulated insulin secretion (GSIS) in MENX rats while insulin sensitivity is improved. In summary, we provide a novel, non-transgenic rat model with high endogenous ghrelin plasma levels and interestingly, improved glucose tolerance. This model might aid in identifying new therapeutic approaches for obesity and obesity-related diseases including type-2 diabetes.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Multiple Endocrine Neoplasia; Agouti-related Protein; Lipid-accumulation; Pancreatic-islets; Acylated Peptide; Neuropeptide-y; Messenger-rna; Beta-cells; Hormone; Humans
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2015
Prepublished im Jahr
HGF-Berichtsjahr
2015
ISSN (print) / ISBN
0012-1797
e-ISSN
1939-327X
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 65,
Heft: 2,
Seiten: 406-420
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
American Diabetes Association
Verlagsort
Alexandria, VA.
Tag d. mündl. Prüfung
0000-00-00
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Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
90000 - German Center for Diabetes Research
Forschungsfeld(er)
Enabling and Novel Technologies
Helmholtz Diabetes Center
PSP-Element(e)
G-500300-001
G-501900-221
Förderungen
Copyright
Erfassungsdatum
2015-11-04