Effect of rat hypothalamic extract administration on insulin secretion in vivo

Supernatants obtained from extracts of both the ventrolateral (VLH) and ventromedial (VMH) hypothalamus of normal rats were found to promote insulin secretion when injected in vivo to normal rats. Catecholamines, acetylcholine, and enkephalins can be excluded as potential candidates in producing the effects of VLH extract administration, since pretreatment of recipient rats with their respective specific blockers (i.e. phentolamine, propranolol, atropine, and naloxone) did not prevent the increase in plasma insulin levels observed after the injection of VLH extracts. In contrast, atropine and propranolol reduced by about 50% the rise in plasma insulin levels that followed the injection of VMH extracts. When extracts of VLH or VMH were partially purified, the insulin-releasing activity was found to correspond, in both cases, to compounds of low molecular weight (i.e. 3600 or lower). Furthermore, digestion of partially purified VLH extracts with trypsin or collagenase markedly decreased their in vivo insulin-promoting activity, suggesting a possible polypeptidic nature of the factor(s) involved. The presence of hypothalamic factor(s), which may conceivably be involved in physiological regulation of insulin secretion, is therefore suggested. This is in keeping with analogous results obtained by other laboratories using different species and experimental conditions.