Insulin Secretion in Response to L-Arginine under Decreasing Tetrahydrobiopterin Content
| Autor: | Ishii Masakazu, Shimizu Shunichi, Watabe Tatsuya, Kiuchi Yuji |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: | |
| Zdroj: | Pteridines, Vol 19, Iss 1, Pp 93-100 (2008) |
| Druh dokumentu: | article |
| ISSN: | 0933-4807 2195-4720 |
| DOI: | 10.1515/pteridines.2008.19.1.93 |
| Popis: | Tetrahydrobiopterin (BH4) content in the pancreas from GK (Goto-Kakizaki) rats as a type II diabetic model was markedly decreased compared to Wistar rats as a healthy control. Moreover, insulin stimulated BH4 synthesis in a hamster pancreatic β-cell line, HIT-T15 cells. Therefore, in diabetic condition, the reduction of insulin action is likely to lead to the low levels of BH4 content in pancreatic β-cells. In this study, we examined the effects of the decrease in BH4 content on insulin secretion by L-arginine (L-Arg) or glucose using HIT-T15 cells. Cytosolic calcium concentration ([Ca2+]i) in HIT-T15 cells was increased by L-Arg. Under the low BH4 content using 2,4- diamino-6-hydroxypyrimidine (DAHP), a selective inhibitor of BH4 synthesis, L-Arg-induced both Ca2+ response and insulin secretion were stimulated. These stimulating effects were recovered by BH4 content recovering, using sepiapterin, a precursor of BH4 biosynthesis. By contrast, glucose-induced Ca2+ response was not affected by the BH4 content. These results suggest that the decrease of BH4 content in β-cells may stimulate insulin secretion by L-Arg, but not by glucose, under diabetic conditions. |
| Databáze: | Directory of Open Access Journals |
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