Nuclear protein p8 is associated with glucose-induced pancreatic β-cell growth

• Published in: Diabetes (New York, N.Y.) Vol. 53; no. 2; p. S82
• Main Authors: Path, Gunter, Opel, Anne, Knoll, Anita, Seufert, Jochen
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01.02.2004
• Subjects: Care and treatment; Dextrose; Diabetes; Glucose; Health aspects; Pancreatic beta cells; Protein kinases; Germany
• ISSN: 0012-1797; 1939-327X

On its own, glucose is a major factor for proliferation of pancreatic β-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 β-cell lines in vitro. Based on this observation, we tested the hypothesis that p8 production in pancreatic β-cells is regulated by glucose. Incubation of rat INS-1 β-cells with 25 mmol/1 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 β-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.