Leptin downregulates ghrelin levels in streptozotocin-induced diabetic mice

Am J Physiol Regul Integr Comp Physiol. 2005 Dec;289(6):R1703-6. doi: 10.1152/ajpregu.00773.2004. Epub 2005 Aug 18.


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. STZ-DM mice 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 x kg(-1) x day(-1) over 7 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 with 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / metabolism*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Ghrelin
  • Injections, Subcutaneous
  • Leptin / administration & dosage*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peptide Hormones / blood*
  • Streptozocin


  • Ghrelin
  • Leptin
  • Peptide Hormones
  • Streptozocin