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We demonstrate that two peptide biased agonists (GEP44 and GEP12) of the GLP-1, neuropeptide Y1, and neuropeptide Y2 receptors (GLP-1R, Y1-R, and Y2-R, respectively) elicit Y1-R antagonist-controlled, GLP-1R-dependent stimulation of insulin secretion in both rat and human pancreatic islets, thus revealing the counteracting effects of Y1-R and GLP-1R agonism

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10 As shown in FIGURE 3 , exenatide normalizes blood glucose levels by reducing fasting and postprandial glucose concentrations through a variety of mechanisms, including enhanced glucose-dependent insulin secretion, regulation of glucagon secretion, delayed gastric emptying, and decreased food intake due to centrally mediated effects on satiety