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

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 mu M arachidonic acid, or 100 mu M carbachol caused a 4.4, 7.0, 4.0 and 4.2 fold, respectively, increase in insulin release (P