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To this effect, the field has generated compelling evidence that beta-cell GLP-1R signaling, mediated by alpha-cell-derived proglucagon products, is an essential component of the adaptation to metabolic stress ( Figure 4 )

That pattern tells a clear story

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In addition, we discuss the increase in the endogenous secretion of this hormone through various stimuli (e.g., carbohydrates, proteins, gut microbiota, bacteria-derived molecules, bile acids, lipids, fatty acids, polyphenols, etc.) or by the increase of GLP-1-producing cells, i.e., L-cells, which can be an appropriate approach for the management of diabetes

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Prospectively, economic studies must evaluate whether earlier intervention might enhance cost-effectiveness by preventing dropout and improving long-term adherence among GLP-1 agonist non-responders