Depletion of the catalytic subunit of protein phosphatase-2A (PP2Ac) markedly attenuates glucose-stimulated insulin secretion in pancreatic beta-cells.
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 beta-(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.
Jangati
Giridhar R
GR
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy, Wayne State University, 259 Mack Avenue, Detroit, MI 48202, USA.
Veluthakal
Rajakrishnan
R
Susick
Laura
L
Gruber
Scott A
SA
Kowluru
Anjaneyulu
A
D000818:Animals; D002999:Clone Cells; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000096:biosynthesis* / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000201:enzymology*; D007515:Islets of Langerhans / Q000166:cytology / Q000201:enzymology; D008297:Male; D054648:Protein Phosphatase 2 / Q000502:physiology*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D007328:Insulin; D054648:Protein Phosphatase 2; D005947:Glucose