INTRACEREBROVENTRICULAR INJECTION OF INSULIN OR GLUCOSE ALTERS INSULIN-LIKE GROWTH FACTOR-II (IGF-II) CONCENTRATIONS IN SPECIFIC HYPOTHALAMIC NUCLEI

Peripherally administered insulin has been shown to after content and gene expression of hypothalamic insulin-like growth factor II (IGF-II) in a region specific manner (Lauterio, T.J. et al., Endocrinology, 126 (1990) 392-398. The objective of this experiment was to determine whether central administration of insulin can modulate hypothalamic IGF-II peptide content. Male Sprague-Dawley rats were implanted with lateral ventricular cannulae and allowed to recover from surgery one week prior to injection. At that point animals were remotely injected with one of the following: (1) synthetic cerebral spinal fluid vehicle (sCSF); (2) 2 mIU porcine insulin (1); (3) glucose (100 mg%) only. Animals were decapitated 30 min after injections and brains were quickly removed, frozen and dissected into specific hypothalamic regions for IGF-II analysis by RIA. Insulin increased IGF-II content in the ventromedial hypothalamic region by 80% (P < 0.001) and paraventricular nucleus by 30% (P < 0.01) compared to sCSF or glucose treatment. Arcuate nucleus and neurointermediary lobe pituitary IGF-II content was decreased with insulin treatment compared to controls (P < 0.01). Insulin had no effect on IGF-II concentrations in the dorsomedial or lateral hypothalamic regions or in the supraoptic and suprachiasmatic nuclei. Peripheral concentrations of glucose, insulin and IGF-II were unaffected by any treatment. Results show that insulin which reaches the brain can alter IGF-II levels in specific regions of the hypothalamus and suggests a possible role for IGF-II in insulin mediated changes in metabolism or hypothalamic hormone secretion.