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BETA
Idevall Hagren, Olof
Alternative names
Publications (10 of 16) Show all publications
Griesche, N., Sanchez, G., Hermans, C. & Idevall Hagren, O. (2019). Cortical mitochondria regulate insulin secretion by local Ca2+ buffering in rodent beta cells. Journal of Cell Science, 132(9), Article ID jcs228544.
Open this publication in new window or tab >>Cortical mitochondria regulate insulin secretion by local Ca2+ buffering in rodent beta cells
2019 (English)In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 132, no 9, article id jcs228544Article in journal (Refereed) Published
Abstract [en]

Mitochondria play an essential role in regulating insulin secretion from beta cells by providing the ATP needed for the membrane depolarization that results in voltage-dependent Ca2+ influx and subsequent insulin granule exocytosis. Ca2+, in turn, is also rapidly taken up by the mitochondria and exerts important feedback regulation of metabolism. The aim of this study was to determine whether the distribution of mitochondria within beta cells is important for the secretory capacity of these cells. We find that cortically localized mitochondria are abundant in rodent beta cells, and that these mitochondria redistribute towards the cell interior following depolarization. The redistribution requires Ca2+-induced remodeling of the cortical F-actin network. Using light-regulated motor proteins, we increased the cortical density of mitochondria twofold and found that this blunted the voltage-dependent increase in cytosolic Ca2+ concentration and suppressed insulin secretion. The activity-dependent changes in mitochondria distribution are likely to be important for the generation of Ca2+ microdomains required for efficient insulin granule release.

Place, publisher, year, edition, pages
COMPANY BIOLOGISTS LTD, 2019
Keywords
Ca2+, Optogenetics, F-actin, Exocytosis, Mitochondria, Insulin
National Category
Cell Biology Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-386181 (URN)10.1242/jcs.228544 (DOI)000468130600013 ()30926624 (PubMedID)
Funder
Swedish Research Council, MH2015-03087Göran Gustafsson Foundation for Research in Natural Sciences and MedicineÅke Wiberg Foundation, M17-0048Novo Nordisk, NNF15OC0016100EXODIAB - Excellence of Diabetes Research in Sweden
Available from: 2019-06-19 Created: 2019-06-19 Last updated: 2019-06-19Bibliographically approved
Xie, B., Nguyen, P. M. & Idevall-Hagren, O. (2019). Feedback regulation of insulin secretion by extended synaptotagmin-1. The FASEB Journal, 33(4), 4716-4728
Open this publication in new window or tab >>Feedback regulation of insulin secretion by extended synaptotagmin-1
2019 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 33, no 4, p. 4716-4728Article in journal (Refereed) Published
Abstract [en]

Endoplasmic reticulum (ER)-plasma membrane (PM) contacts are dynamic structures with important roles in the regulation of calcium (Ca2+) and lipid homeostasis. The extended synaptotagmins (E-Syts) are ER-localized lipid transport proteins that interact with PM phosphatidylinositol 4,5-bisphosphate in a Ca2+-dependent manner. E-Syts bidirectionally transfer glycerolipids, including diacylglycerol (DAG), between the 2 juxtaposed membranes, but the biologic significance of this transport is still unclear. Using insulin-secreting cells and live-cell imaging, we now show that Ca2+-triggered exocytosis of insulin granules is followed, in sequence, by PM DAG formation and E-Syt1 recruitment. E-Syt1 counteracted the depolarization-induced DAG formation through a mechanism that required both voltage-dependent Ca2+ influx and Ca2+ release from the ER. E-Syt1 knockdown resulted in prolonged accumulation of DAG in the PM, resulting in increased glucose-stimulated insulin secretion. We conclude that Ca2+-triggered exocytosis is temporally coupled to Ca2+-triggered E-Syt1 PM recruitment and removal of DAG to negatively regulate the same process.

Keywords
Ca2+, beta-cell, membrane contact sites, TMEM24, PKC
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-382253 (URN)10.1096/fj.201801878R (DOI)000462888500007 ()30589572 (PubMedID)
Funder
Swedish Research Council
Available from: 2019-05-03 Created: 2019-05-03 Last updated: 2019-05-03Bibliographically approved
Fatsis-Kavalopoulos, N., O'Callaghan, P., Xie, B., Hernández Vera, R., Idevall Hagren, O. & Kreuger, J. (2019). Formation of precisely composed cancer cell clusters using a cell assembly generator (CAGE) for studying paracrine signaling at single-cell resolution. Lab on a Chip, 19(6), 1071-1081
Open this publication in new window or tab >>Formation of precisely composed cancer cell clusters using a cell assembly generator (CAGE) for studying paracrine signaling at single-cell resolution
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2019 (English)In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 19, no 6, p. 1071-1081Article in journal (Refereed) Published
Abstract [en]

The function and behaviour of any given cell in a healthy tissue, or in a tumor, is affected by interactions with its neighboring cells. It is therefore important to create methods that allow for reconstruction of tissue niches in vitro for studies of cell-cell signaling and associated cell behaviour. To this end we created the cell assembly generator (CAGE), a microfluidic device which enables the organization of different cell types into precise cell clusters in a flow chamber compatible with high-resolution microscopy. In proof-of-concept paracrine signalling experiments, 4-cell clusters consisting of one pancreatic -cell and three breast cancer cells were formed. It has previously been established that extracellular ATP induces calcium (Ca2+) release from the endoplasmic reticulum (ER) to the cytosol before it is cleared back into the ER via sarcoplasmic/ER Ca2+ ATPase (SERCA) pumps. Here, ATP release from the -cell was stimulated by depolarization, and dynamic changes in Ca2+ levels in the adjacent cancer cells measured using imaging of the calcium indicator Fluo-4. We established that changes in the concentration of cytosolic Ca2+ in the cancer cells were proportional to the distance from the ATP-releasing -cell. Additionally, we established that the relationship between distance and cytosolic calcium changes were dependent on Ca2+-release from the ER using 5-cell clusters composed of one -cell, two untreated cancer cells and two cancer cells pretreated with Thapsigargin (to deplete the ER of Ca2+). These experiments show that the CAGE can be used to create exact cell clusters, which affords precise control for reductionist studies of cell-cell signalling and permits the formation of heterogenous cell models of specific tissue niches.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2019
National Category
Cell Biology
Identifiers
urn:nbn:se:uu:diva-381586 (URN)10.1039/c8lc01153b (DOI)000462666200012 ()30783638 (PubMedID)
Funder
Swedish Cancer Society, CAN 2017/703EU, Horizon 2020, 642866Swedish Research Council, MH2015-03087Göran Gustafsson Foundation for Research in Natural Sciences and Medicine
Available from: 2019-04-12 Created: 2019-04-12 Last updated: 2019-04-24Bibliographically approved
Nguyen, P. M., Gandasi, N., Xie, B., Sugahara, S., Xu, Y. & Idevall Hagren, O. (2019). The PI(4)P phosphatase Sac2 controls insulin granule docking and release. Journal of Cell Biology, 218(11), 3714-3729
Open this publication in new window or tab >>The PI(4)P phosphatase Sac2 controls insulin granule docking and release
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2019 (English)In: Journal of Cell Biology, ISSN 0021-9525, E-ISSN 1540-8140, Vol. 218, no 11, p. 3714-3729Article in journal (Refereed) Published
Abstract [en]

Insulin granule biogenesis involves transport to, and stable docking at, the plasma membrane before priming and fusion. Defects in this pathway result in impaired insulin secretion and are a hallmark of type 2 diabetes. We now show that the phosphatidylinositol 4-phosphate phosphatase Sac2 localizes to insulin granules in a substrate-dependent manner and that loss of Sac2 results in impaired insulin secretion. Sac2 operates upstream of granule docking, since loss of Sac2 prevented granule tethering to the plasma membrane and resulted in both reduced granule density and number of exocytic events. Sac2 levels correlated positively with the number of docked granules and exocytic events in clonal beta cells and with insulin secretion in human pancreatic islets, and Sac2 expression was reduced in islets from type 2 diabetic subjects. Taken together, we identified a phosphoinositide switch on the surface on insulin granules that is required for stable granule docking at the plasma membrane and impaired in human type 2 diabetes.

National Category
Endocrinology and Diabetes Cell Biology
Identifiers
urn:nbn:se:uu:diva-397680 (URN)10.1083/jcb.201903121 (DOI)000494843800017 ()31533953 (PubMedID)
Funder
Swedish Research Council, MH-2015-03087
Available from: 2019-11-28 Created: 2019-11-28 Last updated: 2019-11-28Bibliographically approved
Yang, M., Idevall-Hagren, O., Gylfe, E. & Tengholm, A. (2018). A genetically encoded low-affinity Ca2+ sensor unmasks autocrine purinergic signalling in beta cells. Paper presented at 54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY. Diabetologia, 61, S196-S197
Open this publication in new window or tab >>A genetically encoded low-affinity Ca2+ sensor unmasks autocrine purinergic signalling in beta cells
2018 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S196-S197Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-367135 (URN)000443556002189 ()
Conference
54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY
Available from: 2018-11-29 Created: 2018-11-29 Last updated: 2018-11-29Bibliographically approved
Qi, Y., Chen, J., Liu, X., Zhou, X., Fan, J., Shentu, P., . . . Xu, Y. (2018). Development of a Wireless-Controlled LED Array for the Tunable Optogenetic Control of Cellular Activities. ENGINEERING, 4(6), 745-747
Open this publication in new window or tab >>Development of a Wireless-Controlled LED Array for the Tunable Optogenetic Control of Cellular Activities
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2018 (English)In: ENGINEERING, ISSN 2095-8099, Vol. 4, no 6, p. 745-747Article in journal, Editorial material (Other academic) Published
Abstract [en]

In order to decipher a complex biological process, tools are required to perturb the various players involved to gain information about the important parameters. Optogenetic modules are genetically encoded molecular reagents that, when expressed in cells, allow a specific biological process to be precisely controlled by light in a spatiotemporal manner [1]. Optogenetics thus offers cell biologists an unprecedented new way to perturb cellular activities. The application of optogenetic approaches in cellular biology and synthetic biology research has evolved tremendously in the last few years.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-373075 (URN)10.1016/j.eng.2018.08.005 (DOI)000453056200002 ()
Available from: 2019-01-11 Created: 2019-01-11 Last updated: 2019-01-11Bibliographically approved
Xie, B. & Idevall-Hagren, O. (2018). Extended synaptotagmin-1 controls insulin secretion through diacylglycerol transport at ER-PM contact sites. Paper presented at 54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY. Diabetologia, 61, S72-S72
Open this publication in new window or tab >>Extended synaptotagmin-1 controls insulin secretion through diacylglycerol transport at ER-PM contact sites
2018 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S72-S72Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-367134 (URN)000443556001139 ()
Conference
54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY
Available from: 2018-11-29 Created: 2018-11-29 Last updated: 2018-11-29Bibliographically approved
Nguyen, P. M., Gandasi, N. R. & Idevall-Hagren, O. (2018). The lipid phosphatase INPP5F regulates insulin secretion. Paper presented at 54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY. Diabetologia, 61, S197-S197
Open this publication in new window or tab >>The lipid phosphatase INPP5F regulates insulin secretion
2018 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S197-S197Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-367130 (URN)000443556002190 ()
Conference
54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY
Funder
Swedish Research Council
Available from: 2018-11-29 Created: 2018-11-29 Last updated: 2018-11-29Bibliographically approved
Nguyen, P. M., Xie, B. & Idevall-Hagren, O. (2016). Plasma membrane PI(4,5)P-2 controls Ca2+-influx in clonal beta cells. Paper presented at 52nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 12-16, 2016, Munich, GERMANY. Diabetologia, 59, S189-S190
Open this publication in new window or tab >>Plasma membrane PI(4,5)P-2 controls Ca2+-influx in clonal beta cells
2016 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, p. S189-S190Article in journal (Refereed) Published
Place, publisher, year, edition, pages
SPRINGER, 2016
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-322050 (URN)000398373701191 ()
Conference
52nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 12-16, 2016, Munich, GERMANY
Available from: 2017-05-16 Created: 2017-05-16 Last updated: 2017-05-16Bibliographically approved
Xie, B., Nguyen, P. M., Thonig, A. & Idevall-Hagren, O. (2016). Plasma membrane PI(4,5)P-2 is required for normal glucose-stimulated insulin secretion. Paper presented at 52nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 12-16, 2016, Munich, GERMANY. Diabetologia, 59, S219-S219
Open this publication in new window or tab >>Plasma membrane PI(4,5)P-2 is required for normal glucose-stimulated insulin secretion
2016 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, p. S219-S219Article in journal (Refereed) Published
Place, publisher, year, edition, pages
SPRINGER, 2016
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-322055 (URN)000398373701255 ()
Conference
52nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 12-16, 2016, Munich, GERMANY
Funder
Swedish Research Council
Available from: 2017-05-16 Created: 2017-05-16 Last updated: 2017-05-16Bibliographically approved
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