Studies of immunoreactive insulin secretion in NZO mice in vivo.

Abstract

Studies of immunoreactive insulin (IRI) secretion have been performedin vivo in NZO mice. After an overnight fast, plasma IRI levels were 2–5 times higher in NZO than in control white mice. The IRI response to arginine, 10 mg/kg IV or isoprenaline, 10 Μ/kg IV, was similar in time in the two mice, but IRI increments were greater in the NZO animals. With glucagon 1 Μg/kg IV or aminophylline 25 mg/kg IV the initial secretory response was delayed compared to control mice. Glucose 1.0 g/kg IV elicited a markedly attenuated initial response in NZO mice. When IRI responses were related to basal IRI levels, NZO mice showed smaller initial responses (1–5 min) to all agents tested. Later responses were comparable in the two groups when compared in this way. Diphenylhydantoin, 40 mg/kg administered intraperitoneally 30 min before glucose, 1.0 g/kg IV did not affect glucose-induced insulin secretion in control animals, but abolished it in the NZO mice. These observations suggest the existence of a defect in the IRI release mechanism of the NZOΒ cell situated at a point in the stimulus secretion coupling mechanism common to all the agents examined.