Reduced Pancreatic Content of the Inhibitory Neurotransmitter Galanin in Genetically Obese, Hyperinsulinemic Mice

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Abstract
Because abnormalities of the autonomic nervous system have been described in several animal models of obesity, and because galanin has been proposed to be a sympathetic neurotransmitter in the endocrine pancreas, we hypothesized that the hyperinsulinemia observed in genetically obese (oblob) mice may result either from defective ability of galanin to inhibit insulin release or from a reduced degree of pancreatic galaninergic innervation. To address these possibilities, we examined the effect of exogenous galanin on immuno-reactive insulin (IRI) levels in ob/ob mice and compared the pancreatic content of galaninlike immunoreactivity (GLIR) in oblob mice with that in lean litter-mates. Intravenous administration of synthetic porcine galanin significantly reduced basal IRI levels in oblob mice, suggesting that a defect in galanin action is unlikely to account for the hyperinsulinemia in this model. In contrast, reduced pancreatic galaninergic innervation was supported by findings that pancreatic content of GLIR in ob/ob mice was <10% of that in age- and sex-matched lean littermates. The reduction of pancreatic GLIR in oblob mice appeared organ specific; no such reduction was observed in adrenal GLIR content when comparing obese and lean mice. In addition, the relationship between pancreatic GLIR content and plasma IRI levels was examined in groups of obese and lean mice. It was found in young females, young males, and older mice of mixed sex that there was a significant negative correlation between pancreatic GLIR and plasma IRI in lean mice, whereas no such correlation was observed in obese mice. These findings support the concept that pancreatic galanin plays a role in the normal regulation of insulin release and that a reduced galaninergic innervation contributes to the hyperinsulinemia of the oblob mouse.

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