Nozawa Satoshi, Oda Hitomi, Akiyama Ran, Ueda Kaori, Saeki Kaori, Shono Saori, Maruyama Natsuki, Murata Atsuki, Tazaki Hiroyuki, Mori Akihiro, Momota Yutaka, Azakami Daigo, Sako Toshinori, Ishioka Katsumi
Laboratory of Biomolecular Chemistry, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan.
J Vet Med Sci. 2014 Aug;76(8):1177-82. doi: 10.1292/jvms.14-0033. Epub 2014 May 15.
Hyperadrenocorticism (HAC) is a common endocrine disorder in dogs, in which excess glucocorticoid causes insulin resistance. Disturbance of insulin action may be caused by multiple factors, including transcriptional modulation of insulin signal molecules which lie downstream of insulin binding to insulin receptors. In this study, gene expressions of insulin signal molecules were examined using neutrophils of the HAC dogs (the untreated dogs and the dogs which had been treated with trilostane). Insulin receptor substrate (IRS)-1, IRS-2, phosphatidylinositol 3-kinase (PI3-K), protein kinase B/Akt kinase (Akt)-2 and protein kinase C (PKC)-lambda were analyzed in the HAC dogs and compared with those from normal dogs. The IRS-1 gene expressions decreased by 37% and 35% of the control dogs in the untreated and treated groups, respectively. The IRS-2 gene expressions decreased by 61% and 72%, the PI3-K gene expressions decreased by 47% and 55%, and the Akt-2 gene expressions decreased by 45% and 56% of the control dogs, similarly. Collectively, gene expressions of insulin signal molecules are suppressed in the HAC dogs, which may partially contribute to the induction of insulin resistance.
肾上腺皮质功能亢进（HAC）是犬类常见的内分泌疾病，其中过量的糖皮质激素会导致胰岛素抵抗。胰岛素作用的紊乱可能由多种因素引起，包括胰岛素与胰岛素受体结合后下游胰岛素信号分子的转录调节。在本研究中，使用HAC犬（未治疗犬和已用曲洛司坦治疗的犬）的中性粒细胞检测胰岛素信号分子的基因表达。分析了HAC犬中胰岛素受体底物（IRS）-1、IRS-2、磷脂酰肌醇3-激酶（PI3-K）、蛋白激酶B/Akt激酶（Akt）-2和蛋白激酶C（PKC）-λ，并与正常犬的进行比较。未治疗组和治疗组中，IRS-1基因表达分别下降至对照犬的37%和35%。同样，IRS-2基因表达下降至对照犬的61%和72%，PI3-K基因表达下降至47%和55%，Akt-2基因表达下降至45%和56%。总体而言，HAC犬中胰岛素信号分子的基因表达受到抑制，这可能部分导致了胰岛素抵抗的发生。
