uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Nguyen, Phuoc My
Publications (5 of 5) Show all publications
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
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
Show others...
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
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
Organisations

Search in DiVA

Show all publications