Cytochrome P450 1A-like proteins expressed in the islets of Langerhans and altered pancreatic beta-cell secretory responsiveness

British Journal of Pharmacology
J ClarkeC R Barnett

Abstract

1. The cytochrome P450 (CYP) mixed-function oxidase system is widely distributed in body tissues and plays a key role in the metabolism of endogenous and exogenous compounds. Little attention has been paid to the expression of the system in the islets of Langerhans. The current study has examined the expression and potential role of the CYP1A family within the islets of Langerhans of control and 3-methylcholanthrene (3-MC)-induced Wistar rats. 2. CYP1A expression within pancreatic slices and islets from 3-MC-induced and control rats demonstrated that CYP1A-like protein levels were induced by 3-MC pretreatment (25 mg kg-1 day-1; i.p. for 3 days). 3. Effects of 3-MC-induction on beta-cell secretory responsiveness were investigated by use of rat collagenase-isolated islets. Insulin release from control islets incubated with 3 mM glucose (basal) was 1.4 +/- 0.2 ng/islet h-1 (mean +/- s.e.mean, n = 7). Incubation with 16.7 mM glucose, 25 mM KCl, 100 microM arachidonic acid, or 100 microM carbachol caused a 4.4, 7.0, 4.0 and 4.2 fold, respectively, increase in insulin release (P < 0.001). Forskolin (2 microM), or phorbol 12-myristic 13-acetate (10 nM) potentiated glucose-stimulated insulin release 1.2 and 1.6 fold (P < 0.01) whereas ...Continue Reading

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Citations

Nov 19, 2002·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Alexis B UlrichParviz M Pour
Jul 25, 2009·Drug Metabolism Reviews·Katalin MonostoryZdenek Dvorak
Oct 29, 2008·Transplant International : Official Journal of the European Society for Organ Transplantation·Sung-Hee IhmBernhard J Hering
Feb 18, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Katsuhiko YoshizawaAbraham Nyska

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