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Ultrastructure of islet ghrelin cells in the human fetus

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Abstract

Ghrelin is a peptide hormone predominantly produced in the stomach. Ghrelin expression has also been reported in other tissues including the pancreas. We have reported that ghrelin cells constitute a novel endocrine cell type in the human and the developing rat islets. The cells are most numerous pre- and neonatally and, in humans, constitute 10% of all islet cells from mid-gestation to birth. Since gastric ghrelin expression is low before birth, the islets may be the main source of circulating ghrelin during this time. In the present investigation, we have performed an ultrastructural analysis of pancreatic ghrelin cells in human fetuses by using transmission electron microscopy and immunogold labelling. In addition, morphometrical analysis of secretory granules size was performed. Our data provide evidence for the unique ultrastructural features of ghrelin cells versus other islet cells. Notably, the secretory granules of ghrelin cells were of small size with a mean dense-core diameter of 110 nm. We conclude that ghrelin cells constitute a novel islet cell type, distinct from the previously hormonally characterised islet cell types.

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References

  • Björkqvist M, Dornoville de la Cour C, Zhao CM, Gagnemo-Persson R, Håkanson R, Norlen P (2002) Role of gastrin in the development of gastric mucosa. ECL cells and A-like cells in newborn and young rats. Regul Pept 108:73–82

    Google Scholar 

  • Bordi C, Ferrari C, D‘Adda T, Pilato F, Carfagna G, Bertele A, Missale G (1986) Ultrastructural characterization of fundic endocrine cell hyperplasia associated with atrophic gastritis and hypergastrinaemia. Virchows Arch A Pathol Anat Histopathol 409:335–347

    Article  Google Scholar 

  • Böttcher G, Alumets J, Håkanson R, Sundler F (1986) Co-existence of glicentin and peptide YY in colorectal L-cells in cat and man. An electron microscopic study. Regul Pept 13:283–291

    Article  Google Scholar 

  • Capella C, Hage E, Solcia E, Usellini L (1978) Ultrastructural similarity of endocrine-like cells of the human lung and some related cells of the gut. Cell Tissue Res 186:25–37

    Article  Google Scholar 

  • Chanoine JP, Wong AC (2004) Ghrelin gene expression is markedly higher in fetal pancreas compared to fetal stomach: effect of maternal fasting. Endocrinology 145:3813–3820

    Article  Google Scholar 

  • Date Y, Nakazato M, Hashiguchi S, Dezaki K, Mondal MS, Hosoda H, Kojima M, Kangawa K, Arima T, Matsuo H, Yada T, Matsukura S (2002) Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion. Diabetes 51:124–129

    Google Scholar 

  • Dornonville de la Cour C, Björkqvist M, Sandvik AK, Bakke I, Zhao CM, Chen D, Hakanson R (2001) A-like cells in the rat stomach contain ghrelin and do not operate under gastrin control. Regul Pept 99:141–150

    Article  Google Scholar 

  • Klöppel G, Heitz PU (1984) Nesidioblastosis: a clinical entity with heterogeneous lesions of the pancreas. In: Falkmer S, Håkanson R, Sundler F (eds) Evolution and tumour pathology of the neuroendocrine system. Elsevier, Amsterdam, pp 349–370

    Google Scholar 

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

    Article  Google Scholar 

  • Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB (2004) Ghrelin—a hormone with multiple functions. Front Neuroendocrinol 25:27–68

    Article  Google Scholar 

  • Larsson LI, Sundler F, Håkanson R (1976) Pancreatic polypeptide—a postulated new hormone: identification of its cellular storage site by light and electron microscopic immunocytochemistry. Diabetologia 12:211–226

    Article  Google Scholar 

  • Prado CL, Pugh-Bernard AE, Elghazi L, Sosa-Pineda B, Sussel L (2004) Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development. Proc Natl Acad Sci USA 101:2924–2929

    Article  Google Scholar 

  • Rindi G, Necchi V, Savio A, Torsello A, Zoli M, Locatelli V, Raimondo F, Cocchi D, Solcia E (2002) Characterisation of gastric ghrelin cells in man and other mammals: studies in adult and fetal tissues. Histochem Cell Biol 117:511–519

    Article  Google Scholar 

  • Solcia E, Capella C, Buffa R, Usellini L, Fiocca R, Sessa F (1987) Endocrine cells of the digestive system. In: Johnson LR (ed) Physiology of the gastrointestinal tract. Raven, New York, pp 111–130

    Google Scholar 

  • Sundler F, Håkanson R (1988) Peptide hormone-producing endocrine/paracrine cells in the gastro-entero-pancreatic region. In: Björklund A, Hökfelt T, Owman C (eds) Handbook of chemical neuroanatomy. Elsevier, Amsterdam, pp 219–295

    Google Scholar 

  • Volante M, Allia E, Gugliotta P, Funaro A, Broglio F, Deghenghi R, Muccioli G, Ghigo E, Papotti M (2002) Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors. J Clin Endocrinol Metab 87:1300–1308

    Article  Google Scholar 

  • Wierup N, Sundler F (2004) Circulating levels of ghrelin in human fetuses. Eur J Endocrinol 150:405

    Google Scholar 

  • Wierup N, Svensson H, Mulder H, Sundler F (2002) The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas. Regul Pept 107:63–69

    Article  Google Scholar 

  • Wierup N, Yang S, McEvilly RJ, Mulder H, Sundler F (2004) Ghrelin is expressed in a novel endocrine cell type in developing rat islets and inhibits insulin secretion from INS-1 (832/13) cells. J Histochem Cytochem 52:301–310

    Google Scholar 

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Acknowledgements

We thank Karin Jansner, Erik Carlemalm, Ann-Christin Lindh, Britt-Marie Nilsson and Doris Persson for expert technical assistance.

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Correspondence to Nils Wierup.

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This work was supported by grants from the Swedish Medical Research Council (Project No. 4499), the Royal Physiographic Society and the Novo Nordic, Påhlsson and Gyllenstiernska Krapperup Foundations

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Wierup, N., Sundler, F. Ultrastructure of islet ghrelin cells in the human fetus. Cell Tissue Res 319, 423–428 (2005). https://doi.org/10.1007/s00441-004-1044-x

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