Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Potential Protection Against Type 2 Diabetes in Obesity Through Lower CD36 Expression and Improved Exocytosis in β-Cells

Nagao, Mototsugu LU ; Esguerra, Jonathan L S LU orcid ; Asai, Akira LU ; Ofori, Jones K LU ; Edlund, Anna LU ; Wendt, Anna LU ; Sugihara, Hitoshi ; Wollheim, Claes B LU ; Oikawa, Shinichi and Eliasson, Lena LU orcid (2020) In Diabetes 69(6). p.1193-1205
Abstract

Obesity is a risk factor for type 2 diabetes (T2D); however, not all obese individuals develop the disease. In this study, we aimed to investigate the cause of differential insulin secretion capacity of pancreatic islets from donors with T2D and non-T2D (ND), especially obese donors (BMI ≥30 kg/m2). Islets from obese donors with T2D had reduced insulin secretion, decreased β-cell exocytosis, and higher expression of fatty acid translocase CD36. We tested the hypothesis that CD36 is a key molecule in the reduced insulin secretion capacity. Indeed, CD36 overexpression led to decreased insulin secretion, impaired exocytosis, and reduced granule docking. This was accompanied by reduced expression of the exocytotic proteins SNAP25, STXBP1,... (More)

Obesity is a risk factor for type 2 diabetes (T2D); however, not all obese individuals develop the disease. In this study, we aimed to investigate the cause of differential insulin secretion capacity of pancreatic islets from donors with T2D and non-T2D (ND), especially obese donors (BMI ≥30 kg/m2). Islets from obese donors with T2D had reduced insulin secretion, decreased β-cell exocytosis, and higher expression of fatty acid translocase CD36. We tested the hypothesis that CD36 is a key molecule in the reduced insulin secretion capacity. Indeed, CD36 overexpression led to decreased insulin secretion, impaired exocytosis, and reduced granule docking. This was accompanied by reduced expression of the exocytotic proteins SNAP25, STXBP1, and VAMP2, likely because CD36 induced downregulation of the insulin receptor substrate (IRS) proteins, suppressed the insulin-signaling phosphatidylinositol 3-kinase/AKT pathway, and increased nuclear localization of the transcription factor FoxO1. CD36 antibody treatment of the human β-cell line EndoC-βH1 increased IRS1 and exocytotic protein levels, improved granule docking, and enhanced insulin secretion. Our results demonstrate that β-cells from obese donors with T2D have dysfunctional exocytosis likely due to an abnormal lipid handling represented by differential CD36 expression. Hence, CD36 could be a key molecule to limit β-cell function in T2D associated with obesity.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
69
issue
6
pages
1193 - 1205
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:32198214
  • scopus:85083490218
ISSN
1939-327X
DOI
10.2337/db19-0944
language
English
LU publication?
yes
additional info
© 2020 by the American Diabetes Association.
id
b8c3d508-538d-4555-932a-8295aa676336
date added to LUP
2020-05-22 10:15:59
date last changed
2024-12-12 10:06:33
@article{b8c3d508-538d-4555-932a-8295aa676336,
  abstract     = {{<p>Obesity is a risk factor for type 2 diabetes (T2D); however, not all obese individuals develop the disease. In this study, we aimed to investigate the cause of differential insulin secretion capacity of pancreatic islets from donors with T2D and non-T2D (ND), especially obese donors (BMI ≥30 kg/m2). Islets from obese donors with T2D had reduced insulin secretion, decreased β-cell exocytosis, and higher expression of fatty acid translocase CD36. We tested the hypothesis that CD36 is a key molecule in the reduced insulin secretion capacity. Indeed, CD36 overexpression led to decreased insulin secretion, impaired exocytosis, and reduced granule docking. This was accompanied by reduced expression of the exocytotic proteins SNAP25, STXBP1, and VAMP2, likely because CD36 induced downregulation of the insulin receptor substrate (IRS) proteins, suppressed the insulin-signaling phosphatidylinositol 3-kinase/AKT pathway, and increased nuclear localization of the transcription factor FoxO1. CD36 antibody treatment of the human β-cell line EndoC-βH1 increased IRS1 and exocytotic protein levels, improved granule docking, and enhanced insulin secretion. Our results demonstrate that β-cells from obese donors with T2D have dysfunctional exocytosis likely due to an abnormal lipid handling represented by differential CD36 expression. Hence, CD36 could be a key molecule to limit β-cell function in T2D associated with obesity.</p>}},
  author       = {{Nagao, Mototsugu and Esguerra, Jonathan L S and Asai, Akira and Ofori, Jones K and Edlund, Anna and Wendt, Anna and Sugihara, Hitoshi and Wollheim, Claes B and Oikawa, Shinichi and Eliasson, Lena}},
  issn         = {{1939-327X}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1193--1205}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{Potential Protection Against Type 2 Diabetes in Obesity Through Lower CD36 Expression and Improved Exocytosis in β-Cells}},
  url          = {{http://dx.doi.org/10.2337/db19-0944}},
  doi          = {{10.2337/db19-0944}},
  volume       = {{69}},
  year         = {{2020}},
}