Apolipoprotein A-I primes beta cells to increase glucose stimulated insulin secretion
Nilsson, Oktawia LU ; Del Giudice, Rita LU ; Nagao, Mototsugu LU ; Grönberg, Caitriona LU ; Eliasson, Lena LU
and Lagerstedt, Jens O
LU
(2020)
In Biochimica et Biophysica Acta - Molecular Basis of Disease
1866(3).
- Abstract
The increase of plasma levels of high-density lipoproteins and Apolipoprotein A-I (ApoA-I), its main protein component, has been shown to have a positive action on glucose disposal in type 2 diabetic patients. The current study investigates the unexplored function of ApoA-I to prime beta cells for improved insulin secretion. INS-1E rat clonal beta cells as well as isolated murine islets were used to study the effect of ApoA-I on responsiveness of the beta cells to high glucose challenge. Confocal and transmission electron microscopy were used to dissect ApoA-I mechanisms of action. Chemical endocytosis blockers were used to understand the role of ApoA-I internalization in mediating its positive effect. Pre-incubation of beta cells and... (More)
The increase of plasma levels of high-density lipoproteins and Apolipoprotein A-I (ApoA-I), its main protein component, has been shown to have a positive action on glucose disposal in type 2 diabetic patients. The current study investigates the unexplored function of ApoA-I to prime beta cells for improved insulin secretion. INS-1E rat clonal beta cells as well as isolated murine islets were used to study the effect of ApoA-I on responsiveness of the beta cells to high glucose challenge. Confocal and transmission electron microscopy were used to dissect ApoA-I mechanisms of action. Chemical endocytosis blockers were used to understand the role of ApoA-I internalization in mediating its positive effect. Pre-incubation of beta cells and isolated murine islets with ApoA-I augmented glucose stimulated insulin secretion. This effect appeared to be due to an increased reservoir of insulin granules at the cell membrane, as confirmed by confocal and transmission electron microscopy. Moreover, ApoA-I induced pancreatic and duodenal homeobox 1 (PDX1) shuttling from the cytoplasm to the nucleus, with the subsequent increase in the proinsulin processing enzyme protein convertase 1 (PC1/3). Finally, the blockade of ApoA-I endocytosis in beta cells resulted in a loss of ApoA-I positive action on insulin secretion. The proposed mechanisms of the phenomenon here described include ApoA-I internalization into beta cells, PDX1 nuclear translocation, and increased levels of proinsulin processing enzymes. Altogether, these events lead to an increased number of insulin granules.
(Less)
- author
- Nilsson, Oktawia
LU
; Del Giudice, Rita
LU
; Nagao, Mototsugu
LU
; Grönberg, Caitriona
LU
; Eliasson, Lena
LU
and Lagerstedt, Jens O
LU
- organization
- publishing date
- 2020-03-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Biochimica et Biophysica Acta - Molecular Basis of Disease
- volume
- 1866
- issue
- 3
- article number
- 165613
- publisher
- Elsevier
- external identifiers
-
- pmid:31765698
- scopus:85076238521
- ISSN
- 0925-4439
- DOI
- 10.1016/j.bbadis.2019.165613
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2019 Elsevier B.V. All rights reserved.
- id
- cbcc5fd4-79a3-433b-a04a-1d7f751a4982
- date added to LUP
- 2020-05-11 19:00:32
- date last changed
- 2024-06-26 15:08:39
@article{cbcc5fd4-79a3-433b-a04a-1d7f751a4982,
abstract = {{<p>The increase of plasma levels of high-density lipoproteins and Apolipoprotein A-I (ApoA-I), its main protein component, has been shown to have a positive action on glucose disposal in type 2 diabetic patients. The current study investigates the unexplored function of ApoA-I to prime beta cells for improved insulin secretion. INS-1E rat clonal beta cells as well as isolated murine islets were used to study the effect of ApoA-I on responsiveness of the beta cells to high glucose challenge. Confocal and transmission electron microscopy were used to dissect ApoA-I mechanisms of action. Chemical endocytosis blockers were used to understand the role of ApoA-I internalization in mediating its positive effect. Pre-incubation of beta cells and isolated murine islets with ApoA-I augmented glucose stimulated insulin secretion. This effect appeared to be due to an increased reservoir of insulin granules at the cell membrane, as confirmed by confocal and transmission electron microscopy. Moreover, ApoA-I induced pancreatic and duodenal homeobox 1 (PDX1) shuttling from the cytoplasm to the nucleus, with the subsequent increase in the proinsulin processing enzyme protein convertase 1 (PC1/3). Finally, the blockade of ApoA-I endocytosis in beta cells resulted in a loss of ApoA-I positive action on insulin secretion. The proposed mechanisms of the phenomenon here described include ApoA-I internalization into beta cells, PDX1 nuclear translocation, and increased levels of proinsulin processing enzymes. Altogether, these events lead to an increased number of insulin granules.</p>}},
author = {{Nilsson, Oktawia and Del Giudice, Rita and Nagao, Mototsugu and Grönberg, Caitriona and Eliasson, Lena and Lagerstedt, Jens O}},
issn = {{0925-4439}},
language = {{eng}},
month = {{03}},
number = {{3}},
publisher = {{Elsevier}},
series = {{Biochimica et Biophysica Acta - Molecular Basis of Disease}},
title = {{Apolipoprotein A-I primes beta cells to increase glucose stimulated insulin secretion}},
url = {{http://dx.doi.org/10.1016/j.bbadis.2019.165613}},
doi = {{10.1016/j.bbadis.2019.165613}},
volume = {{1866}},
year = {{2020}},
}