Nuclear protein p8 is associated with glucose-induced pancreatic beta-cell growth.
On its own, glucose is a major factor for proliferation of pancreatic beta-cells and is also an essential prerequisite for IGF-I and growth hormone-induced growth of these cells. p8 was originally identified as an emergency gene product upregulated in pancreatic acinar cells in response to acute pancreatitis. p8 was further shown to be involved in a broad range of biological functions, including cell growth, growth arrest, apoptosis, and tumor development. These in part opposite actions may be related to distinct stimuli and pathways in certain conditions and cell types. Here we demonstrate that p8 is widely expressed in human pancreatic islets in vivo and in several beta-cell lines in vitro. Based on this observation, we tested the hypothesis that p8 production in pancreatic beta-cells is regulated by glucose. Incubation of rat INS-1 beta-cells with 25 mmol/l glucose resulted in a continuous increase of proliferating cell numbers. This was accompanied by a strong upregulation of p8 mRNA and protein expression, indicating that p8 is a physiological mediator of glucose-induced pancreatic beta-cell growth. Binding of glucose-activated protein kinase C (PKC) to two PKC sites within a highly conserved region of the p8 protein may be a possible mechanism linking glucose and p8 pathways leading to proliferation.
Päth
Günter
G
Division of Metabolism, Endocrinology, and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany.
Opel
Anne
A
Knoll
Anita
A
Seufert
Jochen
J
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology* / Q000502:physiology; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005947:Glucose; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C491643:NUPR1 protein, human; C109741:Nupr1 protein, rat