Article

The Reg family member INGAP is a marker of endocrine patterning in the embryonic pancreas.

Department of Internal Medicine, The Strelitz Diabetes Institutes, Eastern Virginia Medical School, Norfolk, VA 23510, USA.
Pancreas (Impact Factor: 3.01). 02/2008; 36(1):1-9. DOI: 10.1097/MPA.0b013r318148c8e6
Source: PubMed

ABSTRACT Adult islet neogenesis is believed to recapitulate elements of pancreatic endocrine development. Identifying factors that regulate islet neogenesis-associated protein (INGAP) gene activity could provide links to pancreas development.
Predicted transcriptional regulators of INGAP were screened in an INGAP-promoter-reporter assay. Based upon their temporal expression, the occurrence of INGAP-positive cells during pancreas embryonic development were studied.
Pancreatic transcription factors, PDX-1, Ngn3, NeuroD, and Isl-1, activated the INGAP promoter, but PAX4, PAX6, and Nkx2.2 did not. The INGAP-positive cells were present in the developing pancreatic bud of the mouse embryo. Emerging clusters of unorganized endocrine cells were INGAP positive. These cells coexpressed insulin or somatostatin, but glucagon-expressing cells remained distinct. The INGAP-positive cells were also detected in the maturing neonatal endocrine cells organized into islets. In direct contrast to the embryo, glucagon localized with most INGAP-positive cells in the postnatal endocrine cells. The INGAP-positive cells juxtaposed pancreatic duct cells. A subset of 5-bromo-2'-deoxyuridine-positive/INGAP-positive cells was detected in the neonatal pancreas.
These data implicate INGAP and/or Reg family proteins in endocrine cell patterning during embryonic development and suggest that INGAP immunoreactivity is a key marker associated with early endocrine cells.

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    • "studies suggest that combinations of inflammation-modulating agents with islet trophic factors may be one approach in the treatment or reversal of T1DM. Islet neogenesis associated protein (INGAP) is a member of the Reg3 family of pancreatic proteins and regulated by transcriptional factors involved in neuroendocrine lineage commitment [7]. In studies of normal hamsters, administration of an INGAP-derived peptide (corresponding to amino acids 104 -118 of INGAP) appeared to stimulate islet neogenesis, as evidenced by small foci of insulin-positive islet-like clusters budding from intralobular and terminal ductules [8]. "
    Journal of Diabetes Mellitus 01/2012; 02(02). DOI:10.4236/jdm.2012.22040
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    • "INGAP was a compound originally identified as part of a protein complex (ilotropin), isolated from pancreata of normal adult hamsters previously wrapped in cellophane [2], and thereafter cloned and sequenced [3]. Lately however, the presence of INGAP was found at the embryonic mouse pancreas commitment period, thus providing evidence of its early normal presence and possible role in pancreas development and patterning [4]. INGAP gene encodes a 19,940 Da transcript [3], only produced in different subsectors of the pancreas (islets, duct and exocrine cells) [5]. "
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