Somatostatin and insulin secretion due to common mechanisms by a new hypoglycemic agent, A-4166, in perfused rat pancreas
| Autor: | Toshio Maki, Megumi Akiyoshi, Toshihiko Yada, Takao Ikenoue, Shoji Fujitani |
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| Rok vydání: | 1996 |
| Předmět: |
Male
medicine.medical_specialty Potassium Channels Time Factors Somatostatin secretion Phenylalanine Endocrinology Diabetes and Metabolism medicine.medical_treatment Nateglinide Biology Glucagon Adenosine Triphosphate Endocrinology Tolbutamide Cyclohexanes Internal medicine Insulin Secretion medicine Diazoxide Animals Hypoglycemic Agents Insulin Rats Wistar Pancreas Pancreatic hormone Delta cell Rats Perfusion Somatostatin Calcium Calcium Channels medicine.drug |
| Zdroj: | Metabolism. 45:184-189 |
| ISSN: | 0026-0495 |
| DOI: | 10.1016/s0026-0495(96)90051-7 |
| Popis: | N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) is a nonsulfonylurea hypoglycemic agent that decreases blood glucose levels in nondiabetic and diabetic animals. In the present study, we attempted to determine the effect of A-4166 on hormone secretion from the in vitro-perfused rat pancreas and to examine the underlying secretory mechanisms. In the presence of basal glucose (3 mmol/L), A-4166 markedly stimulated insulin and somatostatin release in a concentration-dependent manner over 0.03 to 3 mmol/L. A sulfonylurea, tolbutamide, also stimulated insulin and somatostatin release. A-4166 and tolbutamide elevated the level of glucagon release; however, the change lacked a clear concentration-dependent property. A-4166 at 0.3 mmol/L and tolbutamide at 3 mmol/L exhibited maximal stimulation of insulin release to a similar extent, indicating that A-4166 is one log-order more potent than and as effective as tolbutamide. By contrast, A-4166 stimulated somatostatin release to a threefold greater extent than tolbutamide. A-4166 evoked an increase in the cytosolic free-Ca2+ concentration ([Ca2+]i) in rat pancreatic beta cells. [Ca2+]i and insulin secretory responses to A-4166 were inhibited by nitrendipine (NTD), a blocker of the L-type Ca2+ channel, and by diazoxide (DAZ), an opener of the adenosine triphosphate (ATP)-sensitive K+ channel. Furthermore, A-4166-stimulated somatostatin release was also inhibited by NTD and by DAZ. The results indicate that A-4166 and tolbutamide stimulate the release of insulin and somatostatin, and that A-4166 is much more effective than tolbutamide in releasing somatostatin, a hormone that attenuates hyperglycemia under certain circumstances. It is concluded that A-4166-induced insulin release is mediated by an increase in [Ca2+]i in beta cells. An inhibition of ATP-sensitive K+ channels and a consequent activation of L-type Ca2+ channels appear to play a key role not only in insulin secretion from beta cells, but also in somatostatin secretion from delta cells in response to A-4166. |
| Databáze: | OpenAIRE |
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