Ghrelin is dispensable for embryonic pancreatic islet development and differentiation

Hill, John E.; Mastracci, Teresa L.; Vinton, Carol L.; Doyle, Michelle L.; Anderson, Keith R.; Loomis, Zoe; Schrunk, Jessica M.; Minic, Angela; Prabakar, Kamalaveni R.; Pugliese, Alberto; Sun, Yuxian; Smith, Roy G.; Sussel, Lori

doi:10.1016/j.regpep.2009.02.013

Cited by 21 publications

(24 citation statements)

References 40 publications

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“…However, ghrelin null mice showed no perturbation of islet cell populations and structure, indicating that ghrelin is not essential for normal islet formation. In addition, the elimination of ghrelin in Nkx2.2 K/K islets does not restore a-and b-cell populations, confirming that the event responsible for the loss of insulin-and glucagon-producing cells in Nkx2.2 null mice is not the upregulation of ghrelin (Hill et al 2009). …”

Section: Ag Uag and Ob Expression In The Endocrine Pancreasmentioning

confidence: 91%

Unraveling the role of the ghrelin gene peptides in the endocrine pancreas

Granata

Baragli²,

Settanni³

et al. 2010

Journal of Molecular Endocrinology

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The ghrelin gene peptides include acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin (Ob). AG, mainly produced by the stomach, exerts its central and peripheral effects through the GH secretagogue receptor type 1a (GHS-R1a). UAG, although devoid of GHS-R1a-binding affinity, is an active peptide, sharing with AG many effects through an unknown receptor. Ob was discovered as the G-protein-coupled receptor 39 (GPR39) ligand; however, its physiological actions remain unclear. The endocrine pancreas is necessary for glucose homeostasis maintenance. AG, UAG, and Ob are expressed in both human and rodent pancreatic islets from fetal to adult life, and the pancreas is the major source of ghrelin in the perinatal period. GHS-R1a and GPR39 expression has been shown in b-cells and islets, as well as specific binding sites for AG, UAG, and Ob. Ghrelin colocalizes with glucagon in a-islet cells, but is also uniquely expressed in 3-islet cells, suggesting a role in islet function and development. Indeed, AG, UAG, and Ob regulate insulin secretion in b-cells and isolated islets, promote b-cell proliferation and survival, inhibit b-cell and human islet cell apoptosis, and modulate the expression of genes that are essential in pancreatic islet cell biology. They even induce b-cell regeneration and prevent diabetes in streptozotocin-treated neonatal rats. The receptor(s) mediating their effects are not fully characterized, and a signaling crosstalk has been suggested. The present review summarizes the newest findings on AG, UAG, and Ob expression in pancreatic islets and the role of these peptides on b-cell development, survival, and function.

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Section: Ag Uag and Ob Expression In The Endocrine Pancreasmentioning

confidence: 91%

Unraveling the role of the ghrelin gene peptides in the endocrine pancreas

Granata

Baragli²,

Settanni³

et al. 2010

Journal of Molecular Endocrinology

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“…In contrast, numbers of e cells were significantly increased in mice with deletions of Pax4, Pax6, or Nkx2.2, although this is at the expense of other islet cell types [67,68]. Interestingly, lineage-tracing studies demonstrated that e cells are not terminally differentiated endocrine cells, because in the adult mouse pancreas they can give rise to a, Ppy and, to a lesser extent, b cells [69].…”

Section: Ghrelin (E)-expressing Cellsmentioning

confidence: 98%

Pancreatic Stem Cells Remain Unresolved

Jiang

Morahan

2014

Stem Cells and Development

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“…In the developing mouse and rat pancreas, ghrelin can be detected as early as embryonic day E9.5 and E15, respectively, and continues to be expressed throughout gestation, with levels peaking just before birth [Wierup et al, 2004;Jørgensen et al, 2007;Hill et al, 2009]. In the developing human pancreas, ghrelin cells are numerous from midgestation to the early postnatal period, and account for approximately 10% of all islet cells [Wierup et al, 2002].…”

Section: Similar Developmental Patterns Of Ghrelin-and Glucagon-exprementioning

confidence: 99%

“…However, several studies have shown the colocalization of ghrelin with either glucagon or insulin in both the human and rat pancreas [Date et al, 2002;Volante et al, 2002;Walia et al, 2009]. Emerging evidence suggests a lineage relationship among ghrelin-, insulin-and glucagon-producing cells in the developing pancreas [Hill et al, 2009]. The ghrelin-expressing cells appear to replace ␤ -and ␣ -cells in mice lacking the transcription factor Nkx2.2, Pax4 or Pax6.…”

Section: Similar Developmental Patterns Of Ghrelin-and Glucagon-exprementioning

confidence: 99%

Similar Developmental Patterns of Ghrelin- and Glucagon-Expressing Cells in the Human Pancreas

Vignjević

Todorovic

Damjanović

et al. 2012

Cells Tissues Organs

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The pancreas appears to be a major source of ghrelin during fetal development, but the ontogeny of ghrelin cells in the human pancreas and their developmental relationship with α- and β-cells remain largely unknown. In the present study, we examined the dynamics of ghrelin cell growth, colocalization of ghrelin with major pancreatic hormones and defined the similarities and differences among developmental patterns of ghrelin-, glucagon- and insulin-expressing cells in the human pancreas. To this end, paraffin-embedded pancreatic tissue sections from human embryos and fetuses were assessed by immunohistochemistry. Ghrelin-positive cells were first detected in the pancreas of 11-week-old fetuses. With advancing gestational age, both ghrelin- and glucagon-expressing cells were increasingly observed at the periphery of the developing islets, whereas insulin-containing cells were typically found in the islet core. Double immunohistochemistry showed that ghrelin-expressing cells were clearly separate from insulin-, somatostatin- and pancreatic polypeptide-containing cells. In contrast, cells coexpressing ghrelin and glucagon were sporadically detected during both the early and late fetal periods. Furthermore, morphometric analysis revealed a similar trend in the volume density of ghrelin- and glucagon-positive cells, and a contrasting pattern in β-cell density at specific time points during the development of the human pancreas. This study demonstrates that the developmental pattern of ghrelin cells, although clearly distinct, is quite similar to that of glucagon-expressing cells. The obtained findings indicate a close lineage relationship between these cell populations, a functional relationship between their secretory products and an auto/paracrine mode of ghrelin-glucagon interaction in pancreatic development.

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Ghrelin is dispensable for embryonic pancreatic islet development and differentiation

Cited by 21 publications

References 40 publications

Unraveling the role of the ghrelin gene peptides in the endocrine pancreas

Unraveling the role of the ghrelin gene peptides in the endocrine pancreas

Pancreatic Stem Cells Remain Unresolved

Similar Developmental Patterns of Ghrelin- and Glucagon-Expressing Cells in the Human Pancreas

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