Cloning and sequencing of the pancreatic islet neogenesis associated protein (INGAP) gene and its expression in islet neogenesis in hamsters.

Rafaeloff, Ronit; Pittenger, Gary L.; Barlow, Scott W.; Xiao, Qin; Yan, Bingfang; Rosenberg, Lawrence; Duguid, W. P.; Vinik, Aaron I.

doi:10.1172/jci119383

Cited by 213 publications

(161 citation statements)

References 35 publications

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“…The immunocytochemical presence of INGAP has been shown not only in hamsters, but also in the pancreas of normal foetal mice (Rafaeloff-Phail et al 1998a), adult rats (H Del Zotto & C Semakula, unpublished observations), and in human beings (Rafaeloff-Phail et al 1998b, Semakula et al 2002. It has further been reported that INGAP administration to streptozotocin-treated hamsters decreased significantly the percentage of diabetic animals (Rafaeloff et al 1997, Gold et al 1998.…”

Section: Introductionmentioning

confidence: 94%

Expression of islet neogenesis-associated protein in islets of normal hamsters

Flores

García²,

Borelli³

et al. 2003

Journal of Endocrinology

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The aim of the present study was to test the possible presence and expression of islet neogenesis-associated protein (INGAP) in islet cells of normal adult hamsters.Pancreata from normal male Syrian hamsters were removed to perform the following studies. (i) Western blot analysis using the cytosolic fraction from homogenates of isolated islets, exocrine tissue and whole pancreas, and rabbit INGAP-specific antibody. (ii) Immunohistochemical identification of INGAP-positive cells in fixed sections of intact pancreata, fresh and 72 h cultured islets (isolated by collagenase digestion), and smears of exocrine pancreatic cells, using the same INGAP-specific antibody and streptavidin-biotin complex. (iii) RT-PCR using total RNA extracted from isolated islets and from exocrine tissue as template, and a specific pair of primers. (iv) Control of the sequence of the PCR products.INGAP protein was identified by Western blot in the cytosolic fraction of homogenates from fresh isolated islets, exocrine cells and whole fresh pancreas. INGAPimmunopositive cells were observed in duct, exocrine and islet cells in either fixed intact or digested pancreatic tissue. INGAP mRNA was identified in samples of total RNA from fresh and cultured isolated islets and from exocrine cells.Our data demonstrate that INGAP is present and expressed in islets and in exocrine pancreatic cells of normal hamsters. The ubiquitous localization of INGAP suggests its possible role in the physiological process of islet growth and its protective effect upon streptozotocininduced diabetes.

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Section: Introductionmentioning

confidence: 94%

Expression of islet neogenesis-associated protein in islets of normal hamsters

Flores

García²,

Borelli³

et al. 2003

Journal of Endocrinology

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“…Gene expression profiling has identified the Reg3 gene family as potentially involved in the stimulatory effect of RKIP1 ablation on pancreatic growth at P28. Interestingly, the Reg3 genes have been previously associated to pancreatic regeneration and islet cell neogenesis [37][38][39][40][41]. Further supporting a role for Reg3 genes in pancreatic postnatal development, a recent study has described the upregulation of Reg3 genes in the mouse pancreas between P7 and P30 followed by their subsequent downregulation in adulthood [42].…”

Section: Discussionmentioning

confidence: 89%

The role of Raf-1 kinase inhibitor protein in the regulation of pancreatic beta cell proliferation in mice

et al. 2012

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Aims/hypothesis Manoeuvres aimed at increasing beta cell mass have been proposed as regenerative medicine strategies for diabetes treatment. Raf-1 kinase inhibitor protein 1 (RKIP1) is a common regulatory node of the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways and therefore may be involved in regulation of beta cell homeostasis. The aim of this study was to investigate the involvement of RKIP1 in the control of beta cell mass and function. Methods Rkip1 (also known as Pebp1) knockout (Rkip1 −/− ) mice were characterised in terms of pancreatic and glucose homeostasis, including morphological and functional analysis. Glucose tolerance and insulin sensitivity were examined, followed by assessment of glucose-induced insulin secretion in isolated islets and beta cell mass quantification through morphometry. Further characterisation included determination of endocrine and exocrine proliferation, apoptosis, MAPK activation and whole genome gene expression assays. Capacity to reverse a diabetic phenotype was assessed in adult Rkip1 −/− mice after streptozotocin treatment. Results Rkip1 −/− mice exhibit a moderately larger pancreas and increased beta cell mass and pancreatic insulin content, which correlate with an overall improvement in whole body glucose tolerance. This phenotype is established in young postnatal stages and involves enhanced cellular proliferation without significant alterations in cell death. Importantly, adult Rkip1 −/− mice exhibit rapid reversal of streptozotocin-induced diabetes compared with control mice.Electronic supplementary material The online version of this article (doi:10.1007/s00125-012-2696-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users. Conclusions/interpretation These data implicate RKIP1 in the regulation of pancreatic growth and beta cell expansion, thus revealing RKIP1 as a potential pharmacological target to promote beta cell regeneration.

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“…[194][195][196] The expression and secretion of another molecule that belongs to the Reg family of proteins, termed islet neogenesis-associated protein (INGAP), is upregulated in hamster islets where neogenesis was artificially induced. 197,198 The precise role of INGAP on b-cell proliferation and function, however, remains unclear.…”

Section: Stem/progenitor Cellsmentioning

confidence: 99%