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Ghrelin improves growth hormone responses to growth hormone-releasing hormone in a streptozotocin-diabetic model of delayed onset

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Abstract

GH secretion is markedly altered in diabetes mellitus (DM) in both rats and humans, albeit in opposite directions. In the rat, diabetes suppresses pulsatile GH secretion, especially high amplitude pulses, and decreases GH responses to secretagogue, depending inversely on severity of metabolic alteration. In the present study, we wanted to address the GH responses to GHRH and low doses of ghrelin in a streptozotocin (STZ) model of diabetes characterized by the delayed onset of the metabolic alterations. We have shown that the administration of high doses of STZ (90 mg/kg in 0.01M solution of chloride-sodium, ip) to five-day-old pups (n5-STZ) can induce the appearance of a characteristic diabetic syndrome in adult age, the diabetic triad, with elevated plasma glucose levels: polyuria, polydipsia, hyperphagia, and reduced body weight gain. At the age of 3 months, in these n5-STZ male and female rats the GH responses to GHRH (1 µg/kg) and GHRH combined with ghrelin (1 +3 µg/kg) had diminished both in punctual times and in the area under the curve (AUC). However, the combined administration of GHRH and ghrelin, being the more potent stimulus, elicited a synergistic GH response. Thus, male and female rats with delayed onset diabetes displayed an altered GH response to GHRH, although the combined administration of GHRH and ghrelin was able to restore the GH secretion with a synergistic effect.

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Authors and Affiliations

  1. Laboratory of Endocrinology, Department of Functional Biology and Health Sciences, Faculty of Sciences, Campus of Vigo, University of Vigo, Vigo

    Y. Diz-Chaves PhD, C. Spuch, D. Pérez & F. Mallo

  2. Laboratory C-01, Department of Neural Plasticity, Cajal Institute (CSIC), Avda Doctor Arce 37, 28002, Madrid, Spain

    Y. Diz-Chaves PhD

  3. Division of Molecular Neurobiology, Department of Neurosciences, Karolinska Institute, Stockholm, Sweden

    C. Spuch

  4. Department of Psychiatry, Obesity Research Center, Genome Research Institute, Cincinnati, USA

    D. Pérez

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  1. Y. Diz-Chaves PhD
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  2. C. Spuch
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  3. D. Pérez
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  4. F. Mallo
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Correspondence to Y. Diz-Chaves PhD.

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Diz-Chaves, Y., Spuch, C., Pérez, D. et al. Ghrelin improves growth hormone responses to growth hormone-releasing hormone in a streptozotocin-diabetic model of delayed onset. J Endocrinol Invest 30, 298–305 (2007). https://doi.org/10.1007/BF03346307

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