---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '23148'
abstract:
- lang: eng
text: Presenilin-1 (PS1) is an endoplasmic reticulum protein, most known for its
role in pathogenesis of familial Alzheimer’s Disease (AD). PS1 has been attributed
roles in intracellular calcium homeostasis in the brain, as well as in the pancreatic
beta cells, where it has been shown to be fundamental for the initial phase of
glucose-induced insulin secretion. To gain mechanistic insight into beta cell
autonomous function of PS1, we have examined various beta cell models and found
that PS1 controls glycolytic flux of pancreatic beta cells by regulating sub-mitochondrial
Ca2+ homeostasis. Transient knock down of PS1 yielded a glycolytic bottleneck
at the step catalyzed by glyceraldehyde-3-phosphate dehydrogenase, resulting in
defective glucose responsiveness. Moreover, we show that PS1 is needed for the
preservation of beta cell identity, likely due to its role in glycolysis. Finally,
we show that mouse islets from an in vivo model of AD mimic the defective glucose
responsiveness seen in beta cells with transient PS1 knock down, while the identity
loss and whole-body glucose homeostasis are not severely impacted, suggesting
an adaptive response. Thus, the current work highlights beta cell autonomous role
of PS1 and adds a layer of complexity in its impact on whole body metabolism.
acknowledgement: We appreciate the technical assistance from Anna Schreilechner. We
are grateful for support by all members of the animal facility team at IMB, University
of Graz, as well as K. Zierler for assistance with animal licenses. F.M, T.E.,
T.M., T.P., and W.F.G. are grateful to the Austrian Science Fund (FWF) for the excellence
cluster 10.55776/COE14 (MetAGE), which was additionally supported by Land Styria,
Stadt Graz, University of Graz and Medical University of Graz. This research was
further supported by the FWF via the DKplus program 10.55776/W1226 (DK-MCD) to F.M.,
T.M., R.B.G., and W.F.G., 10.55776/P28529, 10.55776/I3716 (to R.M.), 10.55776/P28854,
10.55776/I3792, 10.55776/DOC130 (to T.M.), and 10.55776/I4319 (to. M.S.R.); the
Austrian Research Promotion Agency (FFG) grants 864690 and 870454; the Integrative
Metabolism Research Center Graz; the Austrian Infrastructure Program 2016/2017 (to
T.M.), and 10.55776/COE7, 10.55776/COE17, 10.55776/FG12 and 10.55776/F73 (to R.B.G.);
the Styrian Government; the City of Graz; and BioTechMed-Graz (flagship project)
(to T.M.); the MEFO Graz (to W.F.G.). F.E.O., J.G. and Z.K. were doctoral fellows
in the doctoral program Metabolic and Cardiovascular Disease (MCD) (FWF, 10.55776/W
1226) at the Medical University of Graz. S.v.A. and A.S. are thesis students in
the excellence cluster 10.55776/COE14 (MetAGE, W.F.G.). M.H. was a fellow of the
Molecular Medicine (MolMed) doctoral program at the Medical University of Graz supported
by MEFO Graz. The SIM equipment is part of the Nikon Center of Excellence, Graz,
and is supported by the Austrian infrastructure program 2013/ 2014, Nikon Austria
Inc., and BioTechMed (to W.F.G.). Our thanks go to Shimadzu Austria for supporting
this research through instrument access given in the Metabolomics and Bioprocess
Analytics laboratory (TU Wien) (R.B.G.). For open access purposes, the authors have
applied a CC BY public copyright license to any author-accepted manuscript version
arising from this submission.” We thank the Medical University of Graz for financial
support.
article_number: '1315'
article_processing_charge: Yes
article_type: original
author:
- first_name: Zhanat
full_name: Koshenov, Zhanat
last_name: Koshenov
- first_name: Sandra
full_name: Postic, Sandra
last_name: Postic
- first_name: Gabriela
full_name: Schoiswohl, Gabriela
last_name: Schoiswohl
- first_name: Savina
full_name: Van Amsterdam, Savina
last_name: Van Amsterdam
- first_name: Victoria
full_name: Hois-Zelinka, Victoria
last_name: Hois-Zelinka
- first_name: Furkan E.
full_name: Oflaz, Furkan E.
last_name: Oflaz
- first_name: Rene
full_name: Rost, Rene
last_name: Rost
- first_name: Oleksandra
full_name: Tiapko, Oleksandra
last_name: Tiapko
- first_name: Benjamin
full_name: Gottschalk, Benjamin
last_name: Gottschalk
- first_name: Martin
full_name: Hirtl, Martin
last_name: Hirtl
- first_name: Olaf G.
full_name: Bachkoenig, Olaf G.
last_name: Bachkoenig
- first_name: Aigerim
full_name: Koshenova, Aigerim
last_name: Koshenova
- first_name: Yusuf C.
full_name: Erdogan, Yusuf C.
last_name: Erdogan
- first_name: Adlet
full_name: Sagintayev, Adlet
last_name: Sagintayev
- first_name: Anita
full_name: Krnjic, Anita
last_name: Krnjic
- first_name: Johannes U.
full_name: Pfabe, Johannes U.
last_name: Pfabe
- first_name: Srdjan
full_name: Sarikas, Srdjan
id: 35F0286E-F248-11E8-B48F-1D18A9856A87
last_name: Sarikas
- first_name: Bernhard
full_name: Hochreiter, Bernhard
id: e6cab3de-17f6-11ed-9210-c1e42e045e9d
last_name: Hochreiter
- first_name: Juergen
full_name: Gindlhuber, Juergen
last_name: Gindlhuber
- first_name: Matthias
full_name: Schittmayer, Matthias
last_name: Schittmayer
- first_name: Jelena
full_name: Tadic, Jelena
last_name: Tadic
- first_name: Barbara
full_name: Ehall, Barbara
last_name: Ehall
- first_name: Frank
full_name: Madeo, Frank
last_name: Madeo
- first_name: Tobias
full_name: Madl, Tobias
last_name: Madl
- first_name: Roland
full_name: Malli, Roland
last_name: Malli
- first_name: Ruth
full_name: Birner-Gruenberger, Ruth
last_name: Birner-Gruenberger
- first_name: Thomas
full_name: Pieber, Thomas
last_name: Pieber
- first_name: Tobias
full_name: Eisenberg, Tobias
last_name: Eisenberg
- first_name: Marjan
full_name: Slak Rupnik, Marjan
last_name: Slak Rupnik
- first_name: Wolfgang F.
full_name: Graier, Wolfgang F.
last_name: Graier
citation:
ama: Koshenov Z, Postic S, Schoiswohl G, et al. Presenilin-1 controls glycolysis
and identity of pancreatic beta cells. Communications Biology. 2026;9.
doi:10.1038/s42003-026-10581-6
apa: Koshenov, Z., Postic, S., Schoiswohl, G., Van Amsterdam, S., Hois-Zelinka,
V., Oflaz, F. E., … Graier, W. F. (2026). Presenilin-1 controls glycolysis and
identity of pancreatic beta cells. Communications Biology. Springer Nature.
https://doi.org/10.1038/s42003-026-10581-6
chicago: Koshenov, Zhanat, Sandra Postic, Gabriela Schoiswohl, Savina Van Amsterdam,
Victoria Hois-Zelinka, Furkan E. Oflaz, Rene Rost, et al. “Presenilin-1 Controls
Glycolysis and Identity of Pancreatic Beta Cells.” Communications Biology.
Springer Nature, 2026. https://doi.org/10.1038/s42003-026-10581-6.
ieee: Z. Koshenov et al., “Presenilin-1 controls glycolysis and identity
of pancreatic beta cells,” Communications Biology, vol. 9. Springer Nature,
2026.
ista: Koshenov Z, Postic S, Schoiswohl G, Van Amsterdam S, Hois-Zelinka V, Oflaz
FE, Rost R, Tiapko O, Gottschalk B, Hirtl M, Bachkoenig OG, Koshenova A, Erdogan
YC, Sagintayev A, Krnjic A, Pfabe JU, Sarikas S, Hochreiter B, Gindlhuber J, Schittmayer
M, Tadic J, Ehall B, Madeo F, Madl T, Malli R, Birner-Gruenberger R, Pieber T,
Eisenberg T, Slak Rupnik M, Graier WF. 2026. Presenilin-1 controls glycolysis
and identity of pancreatic beta cells. Communications Biology. 9, 1315.
mla: Koshenov, Zhanat, et al. “Presenilin-1 Controls Glycolysis and Identity of
Pancreatic Beta Cells.” Communications Biology, vol. 9, 1315, Springer
Nature, 2026, doi:10.1038/s42003-026-10581-6.
short: Z. Koshenov, S. Postic, G. Schoiswohl, S. Van Amsterdam, V. Hois-Zelinka,
F.E. Oflaz, R. Rost, O. Tiapko, B. Gottschalk, M. Hirtl, O.G. Bachkoenig, A. Koshenova,
Y.C. Erdogan, A. Sagintayev, A. Krnjic, J.U. Pfabe, S. Sarikas, B. Hochreiter,
J. Gindlhuber, M. Schittmayer, J. Tadic, B. Ehall, F. Madeo, T. Madl, R. Malli,
R. Birner-Gruenberger, T. Pieber, T. Eisenberg, M. Slak Rupnik, W.F. Graier, Communications
Biology 9 (2026).
das_tickbox: '1'
dataavailabilitystatement: The data supporting the findings of this research can be
obtained from the authors upon a reasonable request; please refer to the author’s
contributions for details regarding specific datasets. Numerical source data underlying
graphs in this article can be found in Supplementary data file. Supplementary Figs.
and figure legends are included in the Supplementary file. The code used in this
study is available from the authors on reasonable request.
date_created: 2026-10-18T22:01:50Z
date_published: 2026-10-08T00:00:00Z
date_updated: 2026-10-19T06:23:26Z
day: '08'
ddc:
- '570'
department:
- _id: FISS
doi: 10.1038/s42003-026-10581-6
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fulldoi: https://doi.org/10.1038/s42003-026-10581-6
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intvolume: ' 9'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
pmid: 1
publication: Communications Biology
publication_identifier:
eissn:
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publication_status: published
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: upon request
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status: public
supplementarymaterial: yes
title: Presenilin-1 controls glycolysis and identity of pancreatic beta cells
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
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...