title: Silencing of cytosolic or mitochondrial isoforms of malic enzyme has no effect on glucose-stimulated insulin secretion from rodent islets.
abstract: 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.
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Medical Center, Durham, North Carolina 27704, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Ronnebaum
authors.forename: Mette V
authors.initials: MV
authors.lastname: Jensen
authors.forename: Hans E
authors.initials: HE
authors.lastname: Hohmeier
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Burgess
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Zhou
authors.forename: Su
authors.initials: S
authors.lastname: Qian
authors.forename: Douglas
authors.initials: D
authors.lastname: MacNeil
authors.forename: Andrew
authors.initials: A
authors.lastname: Howard
authors.forename: Nancy
authors.initials: N
authors.lastname: Thornberry
authors.forename: Olga
authors.initials: O
authors.lastname: Ilkayeva
authors.forename: Danhong
authors.initials: D
authors.lastname: Lu
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard