Defects In The Incretin Effect In Type Diabetes

The incretin effect is absent or diminished in type 2 diabetes. GLP-1 still stimulates insulin secretion in type 2 diabetic patients at higher plasma concentrations, whereas GIP has lost most of its insulinotropic activity (27-29). The reason for the loss of the insulinotropic action of GIP has not completely been elucidated yet. Specific defects in GIP signaling and general secretory defects of the beta cell are most likely responsible. GLP-1 secretion as well as GLP-1 action is diminished in type 2 diabetes, but supraphysiological concentrations of GLP-1 by exogenous administration of GLP-1 can restore the defects in the incretin effect. The therapeutic potential of GLP-1 as a pharmacological tool for treating type 2 diabetes has been suggested in the 1990s (29,30). The insulinotropic effect of GLP-1 is only present under hyperglycemic conditions providing the possibility of glucose normalization without the risk of hypoglycemias (29,31). GLP-1 has further physiological actions that may be advantageous in type 2 diabetes therapy.

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