Gluconeogenic Enzymes in β-Cells: Pharmacological Targets for Improving Insulin Secretion

Publication date: Available online 15 June 2019Source: Trends in Endocrinology &MetabolismAuthor(s): Francisco Westermeier, Todd Holyoak, Joel L. Asenjo, Rodrigo Gatica, Francisco Nualart, Ian Burbulis, Romina BertinatPancreatic β-cells express the gluconeogenic enzymes glucose 6-phosphatase (G6Pase), fructose 1,6-bisphosphatase (FBP), and phosphoenolpyruvate (PEP) carboxykinase (PCK), which modulate glucose-stimulated insulin secretion (GSIS) through their ability to reverse otherwise irreversible glycolytic steps. Here, we review current knowledge about the expression and regulation of these enzymes in the context of manipulating them to improve insulin secretion in diabetics. Because the regulation of gluconeogenic enzymes in β-cells is so poorly understood, we propose novel research avenues to study these enzymes as modulators of insulin secretion and β-cell dysfunction, with especial attention to FBP, which constitutes an attractive target with an inhibitor under clinical evaluation at present.
Source: Trends in Endocrinology and Metabolism - Category: Endocrinology Source Type: research

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