Plasma Adiponectin Levels are Increased Despite Insulin Resistance in Corticotropin-releasing Hormone Transgenic Mice, an Animal Model of Cushing Syndrome

Masayuki SHINAHARA; Mitsuru NISHIYAMA; Yasumasa IWASAKI; Shuichi NAKAYAMA; Toru NOGUCHI; Machiko KAMBAYASHI; Yasushi OKADA; Masayuki TSUDA; Mary P. STENZEL-POORE; Kozo HASHIMOTO; Yoshio TERADA

doi:10.1507/endocrj.K09E-038

ORIGINALS

Plasma Adiponectin Levels are Increased Despite Insulin Resistance in Corticotropin-releasing Hormone Transgenic Mice, an Animal Model of Cushing Syndrome

Masayuki SHINAHARA, Mitsuru NISHIYAMA, Yasumasa IWASAKI, Shuichi NAKAYAMA, Toru NOGUCHI, Machiko KAMBAYASHI, Yasushi OKADA, Masayuki TSUDA, Mary P. STENZEL-POORE, Kozo HASHIMOTO, Yoshio TERADA

Author information

Masayuki SHINAHARA
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan
Mitsuru NISHIYAMA
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan
Yasumasa IWASAKI
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan
Shuichi NAKAYAMA
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan
Toru NOGUCHI
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan
Machiko KAMBAYASHI
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan
Yasushi OKADA
Department of Laboratory Animal Science, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan
Masayuki TSUDA
Department of Laboratory Animal Science, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan
Mary P. STENZEL-POORE
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, USA
Kozo HASHIMOTO
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan
Yoshio TERADA
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan

Keywords: Adiponectin, Glucocorticoid, Insulin resistance, Cushing syndrome, Obesity

JOURNAL FREE ACCESS

2009 Volume 56 Issue 7 Pages 879-886

DOI https://doi.org/10.1507/endocrj.K09E-038

View "Advance Publication" version (June 24, 2009).

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Abstract

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±3.1μg/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±0.4μg/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.

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