Hepoxilins raise circulating insulin levels in vivo

FEBS Letters

Demin, Peter M.¹  Estrada, Marvin¹  Liu, Guang-Ying¹  Pace-Asciak, Cecil R.¹ 

[1] Programme in Integrative Biology, Research Institute, Hospital for Sick Children, 555 University Avenue, Toronto, Ont. M5G 1X8, Canada

关键词: Hepoxilin;    Insulin;    Diabetes mellitus;    Calcium;    HxA3;    hepoxilin A3;   

DOI  :  10.1016/S0014-5793(99)01460-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have demonstrated over a decade ago that hepoxilins cause the release of insulin from isolated pancreatic islets of Langerhans in vitro. However, no studies are available so far to indicate whether these compounds are active in vivo. The present study is the first to our knowledge which demonstrates that hepoxilins administered intra-arterially in the anaesthetized rat cause the release of insulin in the circulation. This release is dependent on the glucose status of the rat. Hence, animals fasted overnight do not respond to hepoxilin administration, while animals that have had free access to food respond to hepoxilins with a rise in insulin concentrations in blood. The hepoxilin effect is rapid and varies with different hepoxilins, the most potent of which is hepoxilin A₃ (HxA₃) (both the 8S and the 8R enantiomers). Administration of 100 μg HxA₃ produces a rise in blood insulin equivalent to that caused by the administration of 5 mg glucose. In view of earlier evidence showing that these compounds cause a rise in intracellular calcium levels in vitro at a <1 μg/ml concentration through a receptor-mediated mechanism, we speculate that the actions of hepoxilins in causing the release of insulin from the pancreas may be due to alterations in calcium levels within the β-cell. We believe that hepoxilins may represent new lead compounds as therapeutics in type II diabetes mellitus.

【 授权许可】

Unknown