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http://dx.doi.org/10.5483/BMBRep.2012.45.8.040

Inhibition of glutamate dehydrogenase and insulin secretion by KHG26377 does not involve ADP-ribosylation by SIRT4 or deacetylation by SIRT3  

Kim, Eun-A (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine)
Yang, Seung-Ju (Department of Biomedical Laboratory Science, Konyang University)
Choi, Soo-Young (Department of Biomedical Science, Research Institute for Bioscience and Biotechnology, and Medical & Bio-material Research Center, Hallym University)
Lee, Woo-Je (Department of Internal Medicine, University of Ulsan College of Medicine)
Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine)
Publication Information
BMB Reports / v.45, no.8, 2012 , pp. 458-463 More about this Journal
Abstract
We investigated the mechanisms involved in KHG26377 regulation of glutamate dehydrogenase (GDH) activity, focusing on the roles of SIRT4 and SIRT3. Intraperitoneal injection of mice with KHG26377 reduced GDH activity with concomitant repression of glucose-induced insulin secretion. Consistent with their known functions, SIRT4 ribosylated GDH and reduced its activity, and SIRT3 deacetylated GDH, increasing its activity. However, KHG26377 did not affect SIRT4-mediated ADP-ribosylation/inhibition or SIRT3-mediated deacetylation/activation of GDH. KHG26377 had no effect on SIRT4 protein levels, and did not alter total GDH, acetylated GDH, or SIRT3 protein levels in pancreatic mitochondrial lysates. These results suggest that the mechanism by which KHG26377 inhibits GDH activity and insulin secretion does not involve ADP-ribosylation of GDH by SIRT4 or deacetylation of GDH by SIRT3.
Keywords
ADP-ribosylation; Deacetylation; Glutamate dehydrogenase; Hyperinsulinism; Thiazole derivatives;
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