Rgs16 and Rgs8 in embryonic endocrine pancreas and mouse models of diabetes.
Diabetes is characterized by the loss, or gradual dysfunction, of insulin-producing pancreatic beta-cells. Although beta-cells can replicate in younger adults, the available diabetes therapies do not specifically target beta-cell regeneration. Novel approaches are needed to discover new therapeutics and to understand the contributions of endocrine progenitors and beta-cell regeneration during islet expansion. Here, we show that the regulators of G protein signaling Rgs16 and Rgs8 are expressed in pancreatic progenitor and endocrine cells during development, then extinguished in adults, but reactivated in models of both type 1 and type 2 diabetes. Exendin-4, a glucagon-like peptide 1 (Glp-1)/incretin mimetic that stimulates beta-cell expansion, insulin secretion and normalization of blood glucose levels in diabetics, also promoted re-expression of Rgs16::GFP within a few days in pancreatic ductal-associated cells and islet beta-cells. These findings show that Rgs16::GFP and Rgs8::GFP are novel and early reporters of G protein-coupled receptor (GPCR)-stimulated beta-cell expansion after therapeutic treatment and in diabetes models. Rgs16 and Rgs8 are likely to control aspects of islet progenitor cell activation, differentiation and beta-cell expansion in embryos and metabolically stressed adults.
Villasenor
Alethia
A
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Wang
Zhao V
ZV
Rivera
Lee B
LB
Ocal
Ozhan
O
Asterholm
Ingrid Wernstedt
IW
Scherer
Philipp E
PE
Brekken
Rolf A
RA
Cleaver
Ondine
O
Wilkie
Thomas M
TM
D000375:Aging / Q000187:drug effects / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000196:embryology* / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D000077270:Exenatide; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008820:Mice, Obese; D010455:Peptides / Q000494:pharmacology; D011247:Pregnancy; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D014688:Venoms / Q000494:pharmacology
D010455:Peptides; D020710:RGS Proteins; C107413:RGS16 protein; C542368:RGS8 protein, mouse; D011993:Recombinant Fusion Proteins; D014688:Venoms; D049452:Green Fluorescent Proteins; D000077270:Exenatide