{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T14:36:58Z","timestamp":1759588618861},"reference-count":61,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,5,1]]},"abstract":"<jats:p>Ghrelin and GH secretagogues, including GH-releasing peptide (GHRP)-6, stimulate food intake and adiposity. Because insulin modulates the hypothalamic response to GH secretagogues and acts synergistically with ghrelin on lipogenesis in vitro, we analyzed whether insulin plays a role in the metabolic effects of GHRP-6 in vivo. Streptozotocin-induced diabetic rats received saline, GHRP-6, insulin, or insulin plus GHRP-6 once daily for 8 wk. Rats receiving saline suffered hyperglycemia, hyperphagia, polydipsia, and weight loss. Insulin, but not GHRP-6, improved these parameters (P &amp;lt; 0.001 for all), as well as the diabetes-induced increase in hypothalamic mRNA levels of neuropeptide Y and agouti-related peptide and decrease in proopiomelanocortin. Cocaine amphetamine-related transcript mRNA levels were also reduced in diabetic rats, with GHRP-6 inducing a further decrease (P &amp;lt; 0.03) and insulin an increase. Diabetic rats receiving insulin plus GHRP-6 gained more weight and had increased epididymal fat mass and serum leptin levels compared with all other groups (P &amp;lt; 0.001). In epididymal adipose tissue, diabetic rats injected with saline had smaller adipocytes (P &amp;lt; 0.001), decreased fatty acid synthase (FAS; P &amp;lt; 0.001), and glucose transporter-4 (P &amp;lt; 0.001) and increased hormone sensitive lipase (P &amp;lt; 0.001) and proliferator-activated receptor-\u03b3 mRNA levels (P &amp;lt; 0.01). Insulin normalized these parameters to control values. GHRP-6 treatment increased FAS and glucose transporter-4 gene expression and potentiated insulin\u2019s effect on epididymal fat mass, adipocyte size (P &amp;lt; 0.001), FAS (P &amp;lt; 0.001), and glucose transporter-4 (P &amp;lt; 0.05). In conclusion, GHRP-6 and insulin exert an additive effect on weight gain and visceral fat mass accrual in diabetic rats, indicating that some of GHRP-6\u2019s metabolic effects depend on the insulin\/glucose status.<\/jats:p>","DOI":"10.1210\/en.2009-1394","type":"journal-article","created":{"date-parts":[[2010,3,11]],"date-time":"2010-03-11T03:54:03Z","timestamp":1268279643000},"page":"2008-2018","source":"Crossref","is-referenced-by-count":11,"title":["The Positive Effects of Growth Hormone-Releasing Peptide-6 on Weight Gain and Fat Mass Accrual Depend on the Insulin\/Glucose Status"],"prefix":"10.1210","volume":"151","author":[{"given":"Miriam","family":"Granado","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Hospital Infantil Universitario Nin\u0303o Jesu\u0301s, and Department of Pediatrics, Universidad Auto\u0301noma de Madrid and Centro de Investigacio\u0301n Biome\u0301dica en Red Fisiopatologi\u0301a de Obesidad y Nutricio\u0301n, Instituto de Salud Carlos III, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Garci\u0301a-Ca\u0301ceres","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Hospital Infantil Universitario Nin\u0303o Jesu\u0301s, and Department of Pediatrics, Universidad Auto\u0301noma de Madrid and Centro de Investigacio\u0301n Biome\u0301dica en Red Fisiopatologi\u0301a de Obesidad y Nutricio\u0301n, Instituto de Salud Carlos III, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura M.","family":"Frago","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Hospital Infantil Universitario Nin\u0303o Jesu\u0301s, and Department of Pediatrics, Universidad Auto\u0301noma de Madrid and Centro de Investigacio\u0301n Biome\u0301dica en Red Fisiopatologi\u0301a de Obesidad y Nutricio\u0301n, Instituto de Salud Carlos III, 28009 Madrid, 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