Ghrelin is a gastric peptide with potent or exigenic effects, which has been related to diabetic hyperphagia. Previous data showed that Exendine-4 (Ex-4), a long-lasting action GLP-1 agonist, which resist DPP-IV enzymatic degradation, stimulated insulin secretion, reduces food intake and also reduces blood circulating Ghrelin levels in fasting rats. Some of the effect of EX4 are known o be mediated by changes in the activity of the autonomous nervous system (ANS). EX4 is postulated to have potential therapeutic effects in type II diabetes mellitus.

Specific scientific objectives:
1. To study whether the autonomous nervous system is able to regulate the Ghrelin levels in the rat in ad libitum food intake diet. And to study if the autonomous nervous system activity interferes within the inhibitory effects of Exendin-4 upon Ghrelin levels in the fasting rat, both in normal and diabetics.
2. To study whether Exendin-4 reduces Ghrelin levels in the MKR transgenic mouse, as an optimal model for type II diabetes, and how it could influence diabetic hyperphagia.
3. To study whether Exendin-4 reduces mRNA Ghrelin levels in the stomach in normal rats and in two models of experimental diabetes STZ-treated rats (DM-1) and MKR mice (DM-2).

The inhibitory effect of Ex-4 upon Ghrelin levels, last during four hours, at least, making sense not only affect its secretion by also its production in the stomach, reason by, we propose to evaluate Ghrelin mRNA levels in response to Ex-4 in gastric tissue.