The effect of intravenous injection of Ghrelin on the mean plasma concentrations of insulin in immature camels fed different levels of their energy requirements

Subject Areas : Veterinary Clinical Pathology

Received: 2009-09-28 Accepted : 2010-05-12 Published : 2009-11-22

Keywords: Ghrelin, insulin, Immature camel,

Abstract :

Abstract Ghrelin is a peptide hormone secreted into the circulation from the stomach, but this peptide is also synthetized in a number of different body tissues including the brain and pancreas, suggesting both endocrine and paracrine effects. These include: stimulation of GH and ACTH secretion, an increase in appetite and diabetogenic effect on carbohydrate metabolism. Furthermore, ghrelin is the natural ligand of the growth hormone secretagogue receptor (GHS-R). Ghrelin and its mRNAas well as GH secretagogue receptor mRNAs are expressed in the pancreas and islet cells and regulates insulin release and glucose metabolism, but because the effect of ghrelin on insulin secretion before puberty in semiruminant animals has never been examined,   therefore the purpose of the present research was to determine the effect of ghrelin on insulin secretion before puberty in camels. In this investigation 12 camels were randomly divided into two groups. Animals in each group were fed either 50% and 100% energy content in diet for 2 weeks. After 2 weeks camels received 8 μg ghrelin/kg body weight via their jugular vein for 4 days. Blood samples were collected from the jugular vein of all animals before, during (30 minutes after injection of ghrelin) and after the intervention for 4 continuous days and plasma insulin concentrations determined by RIA. Data obtained were analyzed by repeated measures –ANOVA and paired t-Test. p<0.05 were considered statistically significant. The results of this experiment indicated that the injection of ghrelin significantly decreased the mean plasma concentrations of insulin in pre pubertal camels receiving 50% and 100% dietary energy and there was no significant difference between the two diets regarling this effect.

References:

 

1. Adeghate, E. and Donth T. (1990): Distribution of neuropeptide-Y and vasoactive intestinal polypeptide immunoreactive nerves in normal and transplanted pancreatic tissue. Peptides, 111087-111092.


2. Arvat, E., Di Vito, L., Broglio, F., Papotti, M., Muccioli, G., Dieguez, C., et al. (2000): Preliminary evidence that Ghrelin, the natural GH secretagogue (GHS)-receptor ligand, strongly stimulates GH secretion in humans. Journal of Endocrinological Investigation, 23: 493-495.


3. Arvat, E., Maccario, M., Di Vito, L., Broglio, F., Benso, A., Gottero, C., et al. (2001): Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: Comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone.  Journal of Clinical Endocrinology and Metabolism, 86: 1169-1174.


4. Broglio, F., Arvat, E., Benso, A., Gottero, C., Muccioli, G., Papotti, M., et al. (2001): a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. Journal of Clinical Endocrinology and Metabolism, 86: 5083-5086. 


5. Chen, H.M., Trumbauer, E., Chen, D.T., Weingarth, J.R., and Adams, E.G. (2006): Orexigenic action of peripheral Ghrelin is mediated by neuropeptide Y and agouti-related protein, Endocrinology, 145: 2607-2612.


6. Colombo, M., Gregersen, S., Xiao, J. and Hermansen, K. (2003): Effects of Ghrelin and other neuropeptides (CART, MCH, orexin A and B, and GLP-1) on the release of insulin from isolated rat islets. Pancreas, 27: 61-166.


7. Cowely, M.A., Smart, J.M., Rubinsteni, M., Cerdan, M.G., Diano, S., Horvath, T.L., et al. (2001): Leptin activates anorexigenic POMC neurons through a neural network in arcuate nucleus. Nature, 411: 480-485. 


8. Cummings, D.E., Foster, K.E. Ghrelin-Leptin tango in body-weight regulation. Gastroenterology 124 (2003) 1532-1535. 


9. Daniel, B.W. (2008): A novel, rapid, inhibitory effect of insulin on α1β2γ2s γ-aminobutyric acid type A receptors. Neuroscience letters, 433: 27-31.


10. Date, Y., Nakazato, M., Hashiguchi, S., Dezaki, K., Mondal, M.S., Hosoda, H., et al. (2002): Ghrelin is present in pancreatic α-cells of humans and rats and stimulates insulin secretion. Diabetes, 51: 124-129.


11. Dezaki, K., Hosoda, H., Kakei, M., Hashiguchi, S., Watanabe, M., Kangawa, K., et al. (2004): Endogenous ghrelin in pancreatic islets restricts insulin release by attenuating Ca2+ signaling in β-cells: Implication in the glycemic control in rodents. Diabetes, 53: 3142-3151.


12. Dezaki, K., Kakei, M. and Yada, M. (2007): Ghrelin uses Gα and activates voltage-dependent K channels to attenuate glucose-induced Ca2+ signaling and insulin release in islet β-cells: Novel signal transduction of ghrelin. Diabetes, 56: 2319-2327.


13. Dornonville de la Cour, C., Bjo¨rkqvist, M., Sandvik, A.K., Bakke, I,.Zhao, C.M, Chen, D., et al. (2001): A-like cells in the rat stomach contain ghrelin and do not operate under gastrin control. Regulatory Peptides, 99: 141-150.


14.  Edigo, E.M., Rodriguez-Gallardo, J., Sivestre, R.A. and Marco, J. (2002): Inhibitory effect of ghrelin on insulin and pancreatic somatostatin secration. Endocrinology, 290: 241-244.


15. Gnanapavan, S., Kola, B., Bustin, S.A., Morris, D.G., McGee, P., Fairclough, et al. (2002): The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. Journal of Clinical Endocrinology and Metabolism, 87: 2988-2991. 


16. Gu, X.H., Kurose, T., Kato, S., Masuda, K., Tsuda, K., Ishida, H., et al. (1993): Suppressive effect of GABA on insulin secretion from the pancreatic beta cells in the rat. Life Sci., 52: 687-694.


17. Jian-Lian, G., Hiromi, O., Fumiko, T., Yuri, K., Michiko, Y., Lihua, W., et al. (2005): Synaptic relationships between proopiomelanocortin- and ghrelin-containing neurons in the rat arcuate nucleus. Regulatory peptides, 145: 128-132.


18. Kamegai, J., Tamura, H., Shimizu, T., Ishii, S., Sugihara, H. and Wakabayashi, I. (2001): Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats. Diabetes, 50: 2438-2443.


19. Kohno, D., Nakata, M., Maekawa, F., Fujiwara, K., Maejima, Y., Kuramochi, M., et al. (2007): Leptin suppresses ghrelin-induced activation of neuropeptide Y neurons in the arcuate nucleus via phosphatidylinositol 3-kinase- and phosphodiesterase 3-mediatedpathway. Endocrinology, 148: 2251-2263.


20. Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H. and Kangawa, K. (1999): Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature, 402: 656-660.


21. Kojima, M., Hosoda, H., Sawaguch, A., Mondal, M.S., Suganuma, T. and Matsukura, S. (2000): Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology, 141: 4255-4261.


22. Korbonits, M. and Grossman, A.B. (2004):  Ghrelin: update on a novel hormonal system. European Journal of Endocrinology, 151: S67-S70.


23. Lixin, W., David, H. and Saint-Pierre, Y. (2002): Peripheral ghrelin selectively increases Fos expression in neuropeptide Y – synthesizing neurons in mouse hypothalamic arcuate nucleus. Neuroscience Letters, 325: 47-51.


24. Masafumi, K., Suzuko, H., Masatomo, W., Kenji, K., and Toshihiko, Y. (2008): Ghrelin in Pancreatic Islets Restricts Insulin Release by Attenuating Ca2+ Signaling in ß-Cells. University Graduate School of Medical and Dental Science, 254: 591-598.


25. Masuda, Y., Tanaka, T., Inomata, N., Ohnuma, N., Tanaka, S., Itoh, Z., et al. (2000): Ghrelin stimulates gastric acid secretion and motility in rats. Biochemical and Biophysical Research Communications, 276: 905-908.


26. Moltz, J.H. and McDonald, J.K. (1985):  Neuropeptide Y: direct and indirect action on insulin secretion in the rat. Peptides, 61155-1159.


27. Qader, S.S., Lundquist, I., Ekelund, M., Håkanson, R. and Salehi, A. (2005): Ghrelin activates neuronal constitutive nitric oxide synthase in pancreatic islet cells while inhibiting insulin release and stimulating glucagon release. Department of Surgery, 128(1):51-56.


28. Prado, C.L., Pugh-Bernard, A.E., Elghazi, L., Sosa-Pineda, B. and Sussel, L. (2004): Ghrelin cells replace insulin-producing β cells in two mouse models of pancreas development .Proceedings of the National Academy of Sciences of the United States of America, 101: 2924-2929.


29.  Prodam, F., Bellone, S. and Corneli, G. (2008): Ghrelin: A molecular target for weight regulation, glucose and lipid metabolism. Recent Patents on Endocrine, Metabolic and Immune Drug Discovery, 2(3): 178-193.


30. Shintani, M., Ogawa, Y., Ebihara, K., Aizawae, M., Miyanaga, F., Takaya, K., et al. (2001): Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes, 50: 227-232.


31. Victoria, S., Donna, M. and Simon, M. (2007): Rapid changes in the sensitivity of arcuate nucleus neurons to central ghrelin in relation to feeding status. Physiology and Behavior, 23: 180-185.


32. Von Blankenfeld, G., Turner, J., Ahnert-Hilger, G., John, M., Enkvist, M.O., Stephenson, F., et al. (1995): Expression of functional GABAA receptors in neuroendocrine gastropancreatic cells. Pflugers Arch., 430: 381-388.


33. Waeber, G., Thompson, N. and Waeber, B. (2007): Neuropeptide Y expression and regulation in a differentiated rat insulin-secreting cell. Endocrinology, 133: 1061-1067.


34. Wierup, N., Svensson, H., Mulder, H. and Sundler, F. (2002): The ghrelin cell: A novel developmentally regulated islet cell in the human pancreas. Regulatory Peptides, 107: 63-69.