Insulin suppresses ghrelin-induced [Ca²⁺]i increases in ARC neurons from IRS2 knockout mice.

<p><b><b><i>A and B</i></b></b>: Insulin suppressed ghrelin-induced [Ca²⁺]_i increases in ARC neurons from wild type mice (<i>A</i>, n = 8) and IRS2-KO mice (<i>B</i>, n = 8) in a similar manner. <b><i>C</i></b>: The percentage of insulin-inhibited neurons among ghrelin-activated ARC neurons. The numbers above each bar indicate the number of insulin-inhibited neurons over that of ghrelin-responsive neurons. <b><i>D</i></b>: Hypothetical model for the role of IRS2-dependent insulin reception by vagal afferent NG neurons. In IRS2-KO mice, insulin action to activate nodose ganglion (NG) neurons is severely impaired (Fig. 3C∼E) while insulin action to inhibit first order orexigenic ghrelin-responsive NPY neurons in ARC <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067198#pone.0067198-Maejima1" target="_blank">[18]</a> is intact (Fig. 6A∼C). Hence, hyperphagic obese phenotype parallels with impaired insulin action on NG neurons in IRS2-KO mice. Therefore, the IRS2-dependent reception of insulin by NG neurons could be implicated in the regulation feeding and body weight.