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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Leptin downregulates ghrelin levels in streptozotocin-induced diabetic mice

Department of Internal Medicine 1, Faculty of Medicine, Oita University, Hasama, Oita, Japan

Submitted 4 November 2004 ; accepted in final form 9 August 2005

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·kg^–1·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.

diabetes mellitus; neuropeptide Y