Hypothalamic galanin gene expression and peptide levels in relation to circulating insulin: possible role in energy balance.

Abstract

The peptide galanin (GAL) exists in dense concentrations within the medial hypothalamus and is synthesized in a population of neurons within the paraventricular nucleus (PVN). This peptide has been linked to energy homeostasis through its behavioral, metabolic and endocrine actions, including pancreatic insulin secretion. This investigation examined whether circulating insulin, in turn, has impact on hypothalamic GAL production, GAL mRNA and peptide concentrations in the hypothalamus. Streptozotocin (STZ)-induced diabetic rats, compared to control subjects, were tested with or without insulin replacement. After STZ treatment, the rats exhibited hyperglycemia, increased food and water intake, and decreased weight gain compared to controls. These changes were reversed by daily, subcutaneous injections of insulin. Measurements of GAL mRNA, via solution hybridization/nuclease protection assay, revealed a 6-fold elevation after STZ treatment compared to controls, accompanied by a similar rise in GAL peptide levels. This increase in GAL message and peptide was reversible by insulin and was detected in a mediodorsal hypothalamic (MDH) dissection which contains the PVN. It was not seen in a dissection of the mediobasal hypothalamus that includes the GAL-synthesizing neurons of the arcuate nucleus. Measurements of GAL in discrete hypothalamic nuclei of STZ diabetic rats showed a 100% increase in peptide concentrations (p < 0.05) in the PVN that was insulin responsive. Other hypothalamic areas examined failed to exhibit any change in peptide. These findings are consistent with other evidence indicating an inverse association, between circulating insulin and GAL message or peptide in the PVN, that may have physiological relevance in the control of energy balance.