Abstract

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The stimulation of intracellular pathways through GLP- 1R and GIPR can have either synergistic or opposing modes of action. GLP-1 has multiple actions on a number of tissues and on the endocrine pancreas, but its principal action is potentiation of glucose-induced insulin secretion. Without diabetes, although the predominant effect is the lowering of blood glucose. However, the incretin effect is greatly reduced or even lost inpatients with type 2 diabetes a result that has also been seen in other metabolic disorders such as obesity and insulin resistance. The incretin effect further implies a reduced insulin response to ingested carbohydrates and, subsequently, increased blood glucose levels. What remains unclear is why the incretin effect is reduced in type 2 diabetes. Is it the secretion of incretin hormones themselves or is the action of incretin hormones attenuated. Human studies have shown that the GLP-1 response is certainly reduced in patients with type 2 diabetes vs. subjects with normal glucose metabolism.