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Rgs16 is an early marker for islet formation and beta cell expansion in diabetics
Author(s) -
Ocal Ozhan,
Villasenor Alethia,
Wang Zhao,
Rivera Lee,
Asterholm Ingrid Wernstedt,
Artyukhin Alexander,
Scherer Philipp,
Brekken Rolf,
Cleaver Ondine,
Wilkie Thomas
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.587.1
Subject(s) - endocrinology , medicine , biology , progenitor cell , islet , enteroendocrine cell , beta cell , pancreas , microbiology and biotechnology , green fluorescent protein , stem cell , insulin , hormone , endocrine system , gene , biochemistry
We seek to identify molecular markers of hormone signaling during early physiologic responses to metabolic stress. Regulators of G protein Signaling (RGS) proteins are feedback inhibitors of ligand‐activated G protein‐coupled receptors (GPCR). We characterized Rgs16 gene expression in BAC transgenic GFP reporter mice during pancreatic development and in diabetic mice. Rg16::GFP is first expressed in embryonic pancreas progenitor cells at E9 and then becomes restricted to endocrine cells during later differentiation. Islet expression of Rgs16::GFP is extinguished by two weeks of age (P14) but persists in Vessel‐ and Ductal‐Associated Cells (VDAC) until P28. Pancreatic expression in adults is reactivated in VDAC and beta cells in regenerating islets of hyperglycemic PANIC‐ATTAC mice (type 1 diabetes model) and in obese ob/ob mice (type 2 diabetes model). Elevated glucose and insulin levels correlate with increased Rgs16::GFP expression in ob/ob mice. Exendin‐4, a Glucagon‐like Peptide‐1 (GLP‐1) homolog that stimulates beta‐cell regeneration and normalization of blood glucose levels in type 1 diabetics, promotes pancreatic Rgs16::GFP re‐expression when co‐injected with glucose. Our results suggest that Rgs16 is likely to control aspects of islet progenitor cell activation, differentiation, and beta cell expansion in embryos and metabolically stressed adults. Funding: NIH (GM061395) to TM Wilkie