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The perfused rat pancreas has been used to study the dynamics of insulin release during stimulation with a perifusate of the pituitary neurointermediate lobe (NIP) of genetically obese mice (ob/ob) and their lean litter-mates (+/+). It has been shown that the NIP of ob/ob mice is more active. The remainder of the study was carried out with NIP from ob/ob mice. The results showed that both phases of insulin release stimulated by 16·6 mM-glucose were increased by NIP. When the pancreas was first stimulated with NIP in the presence of 5·5 mM-glucose, followed by a high concentration of glucose, it responded to the latter with a normal biphasic response. If, however, the pancreas was stimulated first with glucose the response to NIP was refractory.

The results are discussed in relation to the possible significance of an insulin secretagogue from the pituitary pars intermedia in the hyperinsulinaemia associated with obesity.