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Figure 2 | BMC Biochemistry

Figure 2

From: The UPS in diabetes and obesity

Figure 2

General scheme of insulin secretion. In the β-cells of the pancreas, elevated blood glucose leads to increased levels of intracellular glucose-6-phosphate. Metabolism of the glucose-6-phosphate through glycolysis and mitochondrial metabolism, leads to increased levels of ATP and to lower levels of ADP. This sequentially results in inhibition of an ATP-sensitive K+ channel, depolarization of the plasma membrane, activation of a voltage-dependent Ca2+ channel, influx of Ca2+ and exocytosis of insulin. Mitochondrial metabolism participates in this process, not only by generating ATP, but also by modulating levels of other metabolites (e.g. GTP, cAMP, NADPH, glutamate, malonyl CoA), which might also contribute to glucose-stimulated insulin secretion. The ATP-sensitive K+ channel and voltage-dependent Ca2+ channel are sites that could be modulated by the ubiquitin proteasome system (UPS). In addition, β-cell survival can be impaired by UPS-mediated degradation of IRS2 in these cells (see text for details).

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