Insulin binding in the hypothalamus of lean and genetically obese Zucker rats

Barbara J. Wilcox, Eric S. Corp, Daniel M. Dorsa, Dianne P. Figlewicz, M. R.C. Greenwood, Stephen C. Woods, Denis G. Baskin

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Recent reports have suggested that the obesity and hyperphagia of the genetically obese Zucker rat may be related to defective insulin action or binding in the hypothalamus. We used quantitative autoradiography to determine if insulin binding is altered in specific hypothalamic nuclei associated with food intake. Insulin binding was measured in the arcuate (ARC), dorsomedial (DMN), and ventromedial (VMN) hypothalamic nuclei of 3-4-month-old lean (Fa/Fa) and genetically obese (fa/fa) Zucker rats. A consistently reproducible 15% increase in the total specific binding of 0.1 nM [125I]-insulin was found in the ARC of the obese genotype. A slight increase in insulin binding in the DMN was also found. No difference in specific insulin binding was found between genotypes in the VMN. Nonlinear least squares analysis of competitive binding studies showed that the Kd of the ARC insulin binding site was 33% higher in the lean rats than in the obese rats, indicating an increased affinity for insulin. No difference in site number (Bmax) was found in the ARC, DMN or VMN, and no evidence was found for reduced insulin binding in the hypothalamus of the obese (fa/fa) genotype. The results suggest that hyperphagia and obesity of the obese (fa/fa) Zucker rat genotype may be associated with increased insulin binding in the arcuate nucleus.

Original languageEnglish (US)
Pages (from-to)1159-1164
Number of pages6
JournalPeptides
Volume10
Issue number6
DOIs
StatePublished - Jan 1 1989

Keywords

  • Arcuate nucleus
  • Brain
  • Hypothalamus
  • Insulin receptors
  • Obesity
  • Quantitative autoradiography
  • Zucker rat

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Wilcox, B. J., Corp, E. S., Dorsa, D. M., Figlewicz, D. P., Greenwood, M. R. C., Woods, S. C., & Baskin, D. G. (1989). Insulin binding in the hypothalamus of lean and genetically obese Zucker rats. Peptides, 10(6), 1159-1164. https://doi.org/10.1016/0196-9781(89)90008-9