Plasma adiponectin levels are increased despite insulin resistance in corticotropin-releasing hormone transgenic mice, an animal model of Cushing syndrome.
Adiponectin (AdN), an adipokine derived from the adipose tissue, has an insulin-sensitizing effect, and plasma AdN is shown to be decreased in obesity and/or insulin resistant state. To clarify whether changes in AdN are also responsible for the development of glucocorticoid-induced insulin resistance, we examined AdN concentration in plasma and AdN expression in the adipose tissue, using corticotropin-releasing hormone (CRH) transgenic mouse (CRH-Tg), an animal model of Cushing syndrome. We found, unexpectedly, that plasma AdN levels in CRHTg were significantly higher than those in wild-type littermates (wild-type: 19.7+/-2.5, CRH-Tg: 32.4+/-3.1 microg/mL, p<0.01). On the other hand, AdN mRNA and protein levels were significantly decreased in the adipose tissue of CRH-Tg. Bilateral adrenalectomy in CRH-Tg eliminated both their Cushing's phenotype and their increase in plasma AdN levels (wild-type/sham: 9.4+/-0.5, CRH-Tg/sham: 15.7+/-2.0, CRH-Tg/ADX: 8.5+/-0.4 microg/mL). These results strongly suggest that AdN is not a major factor responsible for the development of insulin resistance in Cushing syndrome. Our data also suggest that glucocorticoid increases plasma AdN levels but decreases AdN expression in adipocytes, the latter being explained possibly by the decrease in AdN metabolism in the Cushing state.
Shinahara
Masayuki
M
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan.
Nishiyama
Mitsuru
M
Iwasaki
Yasumasa
Y
Nakayama
Shuichi
S
Noguchi
Toru
T
Kambayashi
Machiko
M
Okada
Yasushi
Y
Tsuda
Masayuki
M
Stenzel-Poore
Mary P
MP
Hashimoto
Kozo
K
Terada
Yoshio
Y
D052242:Adiponectin / Q000096:biosynthesis / Q000097:blood*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D003480:Cushing Syndrome / Q000097:blood*; D004195:Disease Models, Animal; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
D052242:Adiponectin; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone