Insulin stimulates inositol incorporation in hippocampus of lean but not obese Zucker rats.
We have previously reported that intraventricular insulin is ineffective in decreasing the body weight of obese (fa/fa) Zucker rats. In the present study, we report that insulin at concentrations of 1 and 5 nM significantly stimulates incorporation of 3H-myoinositol into inositol phosphates (29 +/- 5% and 20 +/- 6% stimulation over control levels) and membrane inositol lipids (29 +/- 4% and 20 +/- 6% stimulation over control levels) within hippocampal slices from lean (Fa/Fa) Zucker rats (n = 3 preparations). Smaller but significant stimulations were observed in the Fa/fa Zucker rat (n = 5) hippocampus [10 +/- 3 and 13 +/- 4% stimulation over control levels (inositol phosphates) and 10 +/- 4 and 14 +/- 3% stimulation over control levels (inositol lipids) with 1 and 5 nM insulin]. Insulin had no effect on 3H-inositol incorporation into hippocampal slices from obese (fa/fa) Zucker rats (n = 5). No difference in insulin binding to hippocampal membranes was observed among the three genotypes. These findings confirm the behavioral observation of insulin insensitivity within the fa/fa Zucker CNS and suggest that this insensitivity may be gene-dose-related.
Figlewicz
D
D
Department of Psychology, University of Washington, Seattle 98195.
Szot
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P
Greenwood
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MR
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D007294:Inositol / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D008563:Membrane Lipids / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D011972:Receptor, Insulin / Q000187:drug effects; D013570:Synaptic Membranes / Q000378:metabolism*
D001786:Blood Glucose; D007295:Inositol Phosphates; D007328:Insulin; D008563:Membrane Lipids; D010716:Phosphatidylinositols; D007294:Inositol; D011972:Receptor, Insulin; D011493:Protein Kinase C