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Further evidence for the regulation of acetyl-CoA carboxylase activity by a glutamate- and magnesium-activated protein phosphatase in the pancreatic β cell

Defective regulation in the diabetic GK rat islet

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Abstract

We previously identified and characterized a glutamateand magnesium-sensitive PP2A-like phosphatase (GAPP), which dephosphorylated and activated acetyl-CoA carboxylase (ACC) in the islet β cell. Herein, we studied potential regulatory mechanisms by which GAPP is activated by glutamate and magnesium, and also quantitated the degree of activation, by glutamate- and magnesium, of ACC in normal rat islets and islets derived from the diabetic Goto-Kakizaki (GK) rat, a model for type 2 diabetes in humans. Our findings indicate that magnesium, but not glutamate, specifically activates the post-translational carboxylmethylation (CML) of the 36 kDa catalytic subunit of GAPP. Okadaic acid (OKA), which inhibits GAPP-mediated activation of ACC, also reduced the magnesium-stimulated CML of the catalytic subunit of GAPP in all the β cell preparations studied. These data suggest that the CML step may be necessary for magnesium- and glutamate-mediated activation of ACC. We also observed a marked attenuation in magnesium-and glutamate-facilitated activation of ACC activity in islets derived from the GK rat. Together, our findings raise an interesting possibility that inhibition of GAPP-catalyzed inactivation of ACC (and subsequent reduction in the generation of long-chain fatty acids) could contribute toward the abnormalities in insulin secretion demonstrable in this animal model for type 2 diabetes.

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Authors and Affiliations

  1. β Cell Biochemistry Laboratory, John D. Dingell VA Medical Center, 48201, Detroit, MI

    Rengasamy Palanivel, Rajakrishnan Veluthakal, Phillip McDonald & Anjaneyulu Kowluru PhD

  2. Department of Pharmaceutical Sciences, 3601, Eugene Applebaum College of Pharmacy, Wayne State University, 259, Mack Avenue, 48202, Detroit, MI

    Rengasamy Palanivel, Rajakrishnan Veluthakal, Phillip McDonald & Anjaneyulu Kowluru PhD

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  1. Rengasamy Palanivel
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  2. Rajakrishnan Veluthakal
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  3. Phillip McDonald
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  4. Anjaneyulu Kowluru PhD
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Correspondence to Anjaneyulu Kowluru PhD.

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These authors contributed equally to this work.

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Palanivel, R., Veluthakal, R., McDonald, P. et al. Further evidence for the regulation of acetyl-CoA carboxylase activity by a glutamate- and magnesium-activated protein phosphatase in the pancreatic β cell. Endocr 26, 71–77 (2005). https://doi.org/10.1385/ENDO:26:1:071

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  • DOI: https://doi.org/10.1385/ENDO:26:1:071

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