Depletion of the catalytic subunit of protein phosphatase-2A (PP2Ac) markedly attenuates glucose-stimulated insulin secretion in pancreatic beta-cells |
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| Authors: | Jangati Giridhar R Veluthakal Rajakrishnan Susick Laura Gruber Scott A Kowluru Anjaneyulu |
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| Affiliation: | (1) Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy, Wayne State University, 259 Mack Avenue, Detroit, MI 48202, USA;(2) β-Cell Biochemistry Laboratory, John D. Dingell VA Medical Center, Detroit, MI, USA;(3) Department of Surgery, Wayne State University, Detroit, MI 48201, USA |
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| Abstract: | Among various phosphatases, the protein phosphatase 2A (PP2A) is relatively well studied in the islet. Previously, we have demonstrated that the catalytic subunit of PP2A (PP2Ac) undergoes okadaic acid (OKA)-sensitive, reversible carboxylmethylation (CML), which appears to be requisite for glucose-stimulated insulin secretion (GSIS). Using the siRNA approach, we examined, herein, the contributory roles of PP2Ac in GSIS from insulin-secreting pancreatic β-(INS-1 832/13) cells. Immunologically, PP2Ac was detectable in all the subcellular fractions studied in rank order of: cytosol > microsomes > secretory granules = nucleus > mitochondria. Transfection of PP2Ac-specific, but not scrambled-siRNA, markedly attenuated PP2A activity and GSIS in these cells. Together, our findings provide a direct evidence for a positive modulatory role for PP2Ac in signaling steps leading to GSIS. |
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| Keywords: | Pancreatic β -cells INS-1 832/13 cells Protein phosphatase 2A Glucose-stimulated insulin secretion |
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