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Silencing of cytosolic or mitochondrial isoforms of malic enzyme has no effect on glucose-stimulated insulin secretion from rodent islets.

Publication ,  Journal Article
Ronnebaum, SM; Jensen, MV; Hohmeier, HE; Burgess, SC; Zhou, Y-P; Qian, S; MacNeil, D; Howard, A; Thornberry, N; Ilkayeva, O; Lu, D; Sherry, AD ...
Published in: J Biol Chem
October 24, 2008

We have previously demonstrated a role for pyruvate cycling in glucose-stimulated insulin secretion (GSIS). Some of the possible pyruvate cycling pathways are completed by conversion of malate to pyruvate by malic enzyme. Using INS-1-derived 832/13 cells, it has recently been shown by other laboratories that NADP-dependent cytosolic malic enzyme (MEc), but not NAD-dependent mitochondrial malic enzyme (MEm), regulates GSIS. In the current study, we show that small interfering RNA-mediated suppression of either MEm or MEc results in decreased GSIS in both 832/13 cells and a new and more glucose- and incretin-responsive INS-1-derived cell line, 832/3. The effect of MEm to suppress GSIS in these cell lines was linked to a substantial decrease in cell growth, whereas MEc suppression resulted in decreased NADPH, shown previously to be correlated with GSIS. However, adenovirus-mediated delivery of small interfering RNAs specific to MEc and MEm to isolated rat islets, while leading to effective suppression of the targets transcripts, had no effect on GSIS. Furthermore, islets isolated from MEc-null MOD1(-/-) mice exhibit normal glucose- and potassium-stimulated insulin secretion. These results indicate that pyruvate-malate cycling does not control GSIS in primary rodent islets.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

October 24, 2008

Volume

283

Issue

43

Start / End Page

28909 / 28917

Location

United States

Related Subject Headings

  • Rats, Sprague-Dawley
  • Rats
  • RNA, Small Interfering
  • Protein Isoforms
  • Models, Biological
  • Mitochondria
  • Mice
  • Male
  • Malate Dehydrogenase
  • Islets of Langerhans
 

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Ronnebaum, S. M., Jensen, M. V., Hohmeier, H. E., Burgess, S. C., Zhou, Y.-P., Qian, S., … Newgard, C. B. (2008). Silencing of cytosolic or mitochondrial isoforms of malic enzyme has no effect on glucose-stimulated insulin secretion from rodent islets. J Biol Chem, 283(43), 28909–28917. https://doi.org/10.1074/jbc.M804665200
Ronnebaum, Sarah M., Mette V. Jensen, Hans E. Hohmeier, Shawn C. Burgess, Yun-Ping Zhou, Su Qian, Douglas MacNeil, et al. “Silencing of cytosolic or mitochondrial isoforms of malic enzyme has no effect on glucose-stimulated insulin secretion from rodent islets.J Biol Chem 283, no. 43 (October 24, 2008): 28909–17. https://doi.org/10.1074/jbc.M804665200.
Ronnebaum SM, Jensen MV, Hohmeier HE, Burgess SC, Zhou Y-P, Qian S, et al. Silencing of cytosolic or mitochondrial isoforms of malic enzyme has no effect on glucose-stimulated insulin secretion from rodent islets. J Biol Chem. 2008 Oct 24;283(43):28909–17.
Ronnebaum, Sarah M., et al. “Silencing of cytosolic or mitochondrial isoforms of malic enzyme has no effect on glucose-stimulated insulin secretion from rodent islets.J Biol Chem, vol. 283, no. 43, Oct. 2008, pp. 28909–17. Pubmed, doi:10.1074/jbc.M804665200.
Ronnebaum SM, Jensen MV, Hohmeier HE, Burgess SC, Zhou Y-P, Qian S, MacNeil D, Howard A, Thornberry N, Ilkayeva O, Lu D, Sherry AD, Newgard CB. Silencing of cytosolic or mitochondrial isoforms of malic enzyme has no effect on glucose-stimulated insulin secretion from rodent islets. J Biol Chem. 2008 Oct 24;283(43):28909–28917.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

October 24, 2008

Volume

283

Issue

43

Start / End Page

28909 / 28917

Location

United States

Related Subject Headings

  • Rats, Sprague-Dawley
  • Rats
  • RNA, Small Interfering
  • Protein Isoforms
  • Models, Biological
  • Mitochondria
  • Mice
  • Male
  • Malate Dehydrogenase
  • Islets of Langerhans