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Am J Physiol Regul Integr Comp Physiol (August 18, 2005). doi:10.1152/ajpregu.00773.2004
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Submitted on November 15, 2004
Accepted on August 9, 2005

Leptin Downregulates Ghrelin Levels in Streptozotocin -induced Diabetic Mice

Tetsuo Tsubone1, Takayuki Masaki1, Isao Katsuragi1, Katsuhiro Tanaka1, Tetsuya Kakuma1, and Hironobu Yoshimatsu1*

1 Department of Internal medicine 1, Oita university, Hasama, Oita, Japan

* To whom correspondence should be addressed. E-mail: hiroy{at}med.oita-u.ac.jp.

Ghrelin, an orexigenic peptide produced in the stomach, is increased in streptozotocin (STZ)-induced diabetic (DM) mice. This study clarifies the regulation of ghrelin levels by leptin in STZ-DM mice, which had higher plasma ghrelin concentrations and greater ghrelin mRNA expression than control mice. Changes in ghrelin levels were dose-dependently attenuated by the subcutaneous injection of leptin (0-27 nmol/kg/day over seven days). Leptin treatment also partially reversed the hyperphagia and hyperglycemia observed in STZ-DM mice, but not the hypoinsulinemia, and there was a decrease in plasma ghrelin concentrations and ghrelin mRNA levels compared to STZ-LEP pair-fed mice. These results indicate that leptin treatment partially reverses elevated plasma ghrelin levels in STZ-DM mice independent of food intake and insulin, and suggest that hypoleptinemia in STZ-DM mice upregulates ghrelin.






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