Characterization of the expression, localization, and secretion of  PANDER in  alpha-cells.
The novel islet-specific protein PANcreatic DERived Factor (PANDER; FAM3B) has been extensively characterized with respect to the beta-cell, and these studies suggest a potential function for PANDER in the regulation of glucose homeostasis. Little is known regarding PANDER in pancreatic -cells, which are critically involved in maintaining euglycemia. Here we present the first report elucidating the expression and regulation of PANDER within the alpha-cell. Pander mRNA and protein are detected in alpha-cells, with primary localization to a glucagon-negative granular cytosolic compartment. PANDER secretion from alpha-cells is nutritionally and hormonally regulated by l-arginine and insulin, demonstrating similarities and differences with glucagon. Signaling via the insulin receptor (IR) through the PI3K and Akt/PKB node is required for insulin-stimulated PANDER release. The separate localization of PANDER and glucagon is consistent with their differential regulation, and the effect of insulin suggests a paracrine/endocrine effect on PANDER release. This provides further insight into the potential glucose-regulatory role of PANDER.
Carnegie
Jason R
JR
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104-4318, USA. carnegie@email.chop.edu
Robert-Cooperman
Claudia E
CE
Wu
Jianmei
J
Young
Robert A
RA
Wolf
Bryan A
BA
Burkhardt
Brant R
BR
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D050416:Glucagon-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D017404:In Situ Hybridization, Fluorescence; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019899:Paracrine Communication / Q000187:drug effects / Q000502:physiology; D014018:Tissue Distribution
D016207:Cytokines; D007328:Insulin; C504749:PANDER protein, mouse; D001120:Arginine; D005947:Glucose