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Hepoxilins raise circulating insulin levels in vivo
C R Pace-Asciak1, P M Demin, M Estrada
1Programme in Integrative Biology, Research Institute, Hospital for Sick Children, 555 University Avenue, Toronto, Ont., Canada.
FEBS Letters
|November 24, 1999
Summary
Hepoxilins stimulate insulin release in vivo in rats, but only when fed. This discovery offers potential new treatments for type II diabetes mellitus.
Area of Science:
- Endocrinology
- Pharmacology
- Metabolism
Background:
- Hepoxilins were previously shown to induce insulin release from pancreatic islets in vitro.
- The in vivo activity and physiological relevance of hepoxilins remained uninvestigated.
Purpose of the Study:
- To investigate the in vivo effects of hepoxilins on insulin secretion in rats.
- To determine the influence of glucose status on hepoxilin-induced insulin release.
Main Methods:
- Intra-arterial administration of hepoxilins in anesthetized rats.
- Measurement of circulating insulin concentrations.
- Comparison of responses in fasted versus fed animals.
Main Results:
- Hepoxilins administered intra-arterially stimulated insulin release in fed rats.
- Fasted rats did not exhibit an insulin response to hepoxilin administration.
- Hepoxilin A(3) (HxA(3)) was identified as the most potent hepoxilin, with effects comparable to glucose administration.
Conclusions:
- Hepoxilins are active in vivo, stimulating insulin release in a glucose-dependent manner.
- The mechanism may involve alterations in intracellular calcium levels in pancreatic beta-cells.
- Hepoxilins show promise as potential therapeutic leads for type II diabetes mellitus.