Nitric oxide stimulates insulin release in liver cells expressing human insulin.
The establishment of surrogate islet beta cells is important for the treatment of diabetes. Hepatocytes have a similar glucose sensing system as beta cells and have the potential to serve as surrogate beta cells. In this report, we demonstrate that infection of Hepa1-6 liver cells with a lentivirus expressing the human insulin cDNA results in expression and secretion of human insulin. Furthermore, we show that l-arginine at low levels of glucose significantly stimulates the release of insulin from these cells, compared to exposure to high concentration of glucose. The arginine-induced insulin release is via the production of nitric oxide, since treatment with N(G)-nitro-l-arginine, an inhibitor of nitric oxide synthase, blocks insulin secretion induced by l-arginine. These results indicate that nitric oxide plays a role in l-arginine-stimulated insulin release in hepatocytes expressing the human insulin gene, and provides a new strategy to induce insulin secretion from engineered non-beta cells.
Qian
Qingwen
Q
Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA.
Williams
John P
JP
Karounos
Dennis G
DG
Ozcan
Sabire
S
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000378:metabolism*; D000078790:Insulin Secretion; D016086:Lentivirus / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D015398:Signal Transduction
D018076:DNA, Complementary; D007328:Insulin; D009569:Nitric Oxide; D011189:Potassium Chloride; D001120:Arginine; D005947:Glucose