Decreased gene expressions of insulin signal molecules in canine hyperadrenocorticism.
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.
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.
Satoshi
S
Nozawa
Hitomi
H
Oda
Ran
R
Akiyama
Kaori
K
Ueda
Kaori
K
Saeki
Saori
S
Shono
Natsuki
N
Maruyama
Atsuki
A
Murata
Hiroyuki
H
Tazaki
Akihiro
A
Mori
Yutaka
Y
Momota
Daigo
D
Azakami
Toshinori
T
Sako
Katsumi
K
Ishioka
D000308:Adrenocortical Hyperfunction / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D000818:Animals; D017931:DNA Primers / Q000235:genetics; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000627:therapeutic use; D004283:Dog Diseases / Q000188:drug therapy* / Q000378:metabolism*; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018709:Statistics, Nonparametric; D000099293:Protein Kinase C-lambda
D017931:DNA Primers; D013196:Dihydrotestosterone; D055504:Insulin Receptor Substrate Proteins; D007527:Isoenzymes; D058539:Phosphatidylinositol 3-Kinase; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D000099293:Protein Kinase C-lambda; C009954:trilostane