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Our data show the presence of leptin receptor immunoreactivity in the endocrine pancreas suggesting that leptin may act at a peripheral level as previously postulated in mammals. The effects of short\u2010 and long\u2010term and dose\u2013response treatment with supraphysiological concentrations of leptin on circulating levels of insulin, glucagon and glucose in the blood have been evaluated. Taken together, our results indicate that leptin treatment was followed by an increase in insulin, glucagon and glucose in the blood, depending on the dose of leptin. Moreover, leptin treatment brought about a decrease of glycogen and the appearance of tyrosine\u2010phosphorylated proteins in the liver. This study shows that in the lizard <jats:italic>P. sicula<\/jats:italic> leptin is involved in glucose metabolism. <jats:italic>J. Exp. 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