PMID- 12401716
OWN - NLM
STAT- MEDLINE
DCOM- 20021209
LR  - 20191210
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 51
IP  - 11
DP  - 2002 Nov
TI  - SERCA3 ablation does not impair insulin secretion but suggests distinct roles of 
      different sarcoendoplasmic reticulum Ca(2+) pumps for Ca(2+) homeostasis in 
      pancreatic beta-cells.
PG  - 3245-53
AB  - Two sarcoendoplasmic reticulum Ca(2+)-ATPases, SERCA3 and SERCA2b, are expressed 
      in pancreatic islets. Immunocytochemistry showed that SERCA3 is restricted to 
      beta-cells in the mouse pancreas. Control and SERCA3-deficient mice were used to 
      evaluate the role of SERCA3 in beta-cell cytosolic-free Ca(2+) concentration 
      ([Ca(2+)](c)) regulation, insulin secretion, and glucose homeostasis. Basal 
      [Ca(2+)](c) was not increased by SERCA3 ablation. Stimulation with glucose 
      induced a transient drop in basal [Ca(2+)](c) that was suppressed by inhibition 
      of all SERCAs with thapsigargin (TG) but unaffected by selective SERCA3 ablation. 
      Ca(2+) mobilization by acetylcholine was normal in SERCA3-deficient beta-cells. 
      In contrast, [Ca(2+)](c) oscillations resulting from intermittent 
      glucose-stimulated Ca(2+) influx and [Ca(2+)](c) transients induced by pulses of 
      high K(+) were similarly affected by SERCA3 ablation or TG pretreatment of 
      control islets; their amplitude was increased and their slow descending phase 
      suppressed. This suggests that, during the decay of each oscillation, the 
      endoplasmic reticulum releases Ca(2+) that was pumped by SERCA3 during the 
      upstroke phase. SERCA3 ablation increased the insulin response of islets to 15 
      mmol/l glucose. However, basal and postprandial plasma glucose and insulin 
      concentrations in SERCA3-deficient mice were normal. In conclusion, SERCA2b, but 
      not SERCA3, is involved in basal [Ca(2+)](c) regulation in beta-cells. SERCA3 
      becomes operative when [Ca(2+)](c) rises and is required for normal [Ca(2+)](c) 
      oscillations in response to glucose. However, a lack of SERCA3 is insufficient in 
      itself to alter glucose homeostasis or impair insulin secretion in mice.
FAU - Arredouani, Abdelilah
AU  - Arredouani A
AD  - Unite d'Endocrinologie et Metabolisme, University of Louvain Faculty of Medicine, 
      Brussels, Belgium.
FAU - Guiot, Yves
AU  - Guiot Y
FAU - Jonas, Jean-Christophe
AU  - Jonas JC
FAU - Liu, Lynne H
AU  - Liu LH
FAU - Nenquin, Myriam
AU  - Nenquin M
FAU - Pertusa, Jose A
AU  - Pertusa JA
FAU - Rahier, Jacques
AU  - Rahier J
FAU - Rolland, Jean-Francois
AU  - Rolland JF
FAU - Shull, Gary E
AU  - Shull GE
FAU - Stevens, Martine
AU  - Stevens M
FAU - Wuytack, Frank
AU  - Wuytack F
FAU - Henquin, Jean-Claude
AU  - Henquin JC
FAU - Gilon, Patrick
AU  - Gilon P
LA  - eng
GR  - HL61974/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Insulin)
RN  - 0 (Isoenzymes)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
RN  - EC 7.2.2.10 (Atp2a3 protein, mouse)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - IY9XDZ35W2 (Glucose)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*metabolism
MH  - Calcium Signaling/physiology
MH  - Calcium-Transporting ATPases/*deficiency/*genetics/*metabolism
MH  - Exons
MH  - Glucose/physiology
MH  - Homeostasis
MH  - Immunohistochemistry
MH  - Insulin/*metabolism
MH  - Insulin Secretion
MH  - Islets of Langerhans/cytology/enzymology/*physiology
MH  - Isoenzymes/genetics
MH  - Kinetics
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases
MH  - Time Factors
EDAT- 2002/10/29 04:00
MHDA- 2002/12/10 04:00
CRDT- 2002/10/29 04:00
PHST- 2002/10/29 04:00 [pubmed]
PHST- 2002/12/10 04:00 [medline]
PHST- 2002/10/29 04:00 [entrez]
AID - 10.2337/diabetes.51.11.3245 [doi]
PST - ppublish
SO  - Diabetes. 2002 Nov;51(11):3245-53. doi: 10.2337/diabetes.51.11.3245.