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  • Title: Serum ghrelin concentrations are increased in children with growth hormone insensitivity and decrease during long-term insulinlike growth factor-I treatment.
    Author: Uckun-Kitapci A, Haqq AM, Purnell JQ, Newcomb K, Gulkesen H, Underwood LE.
    Journal: J Investig Med; 2008 Jan; 56(1):26-31. PubMed ID: 18317425.
    Abstract:
    BACKGROUND: Ghrelin increases food intake, body weight, and growth hormone (GH) secretion. Serum concentrations of ghrelin are low in obese hyperinsulinemic persons, are reduced by infusion of insulin into normal-weight subjects, and are increased in underweight hypoinsulinemic patients with anorexia nervosa. Laron syndrome is an autosomal recessive disorder of GH insensitivity that results in decreased insulinlike growth factor-I (IGF-I) synthesis and growth failure. These patients have elevated GH levels, excess adipose tissue, and are insulin resistant. Because IGF-I has insulinlike actions and patients with GH insensitivity syndrome (GHIS) exhibit excess adiposity, we sought to determine whether ghrelin levels were elevated in these patients and potentially regulated by IGF-I replacement. METHODS: Thirteen children with GHIS and 20 normal control children matched for age, sex, and body mass index underwent complete physical examination and a fasting blood draw at baseline. The GHIS subjects then underwent follow-up fasting blood draws during therapy with human recombinant IGF-I (80-120 mug/kg, given subcutaneously twice daily). Fasting glucose, insulin, and IGF-I concentrations were measured at the time of collection. Fasting total ghrelin levels were measured on stored serum samples. RESULTS: The GHIS subjects had 2-fold higher fasting ghrelin levels (2926 +/- 1869 pg/mL) compared with the normal control children (1492 +/- 493 pg/mL; P = 0.009), and mean ghrelin values were reduced 56% during 6.4 +/- 0.2 years of IGF-I replacement (P < 0.05). CONCLUSIONS: Growth hormone resistance and low IGF-I levels are associated with elevated ghrelin levels, which may potentiate GH secretion and adiposity in these children. Suppression of ghrelin during IGF-I treatment suggests a novel mechanism potentially regulating ghrelin levels.
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