Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Overexpressed beta cell CART increases insulin secretion in mouse models of insulin resistance and diabetes

Abels, Mia LU ; Riva, Matteo LU ; Shcherbina, Liliya LU ; Fischer, Ann Helen Thorén LU ; Banke, Elin LU ; Degerman, Eva LU orcid ; Lindqvist, Andreas LU and Wierup, Nils LU (2022) In Peptides 151.
Abstract

Impaired beta cell function and beta cell death are key features of type 2 diabetes (T2D). Cocaine- and amphetamine-regulated transcript (CART) is necessary for normal islet function in mice. CART increases glucose-stimulated insulin secretion in vivo in mice and in vitro in human islets and CART protects beta cells against glucotoxicity-induced cell death in vitro in rats. Furthermore, beta cell CART is upregulated in T2D patients and in diabetic rodent models as a consequence of hyperglycaemia. The aim of this study was to assess the impact of upregulated beta cell CART on islet hormone secretion and glucose homeostasis in a transgenic mouse model. To this end, mice with beta cell-specific overexpression of CART (CARTtg mice) were... (More)

Impaired beta cell function and beta cell death are key features of type 2 diabetes (T2D). Cocaine- and amphetamine-regulated transcript (CART) is necessary for normal islet function in mice. CART increases glucose-stimulated insulin secretion in vivo in mice and in vitro in human islets and CART protects beta cells against glucotoxicity-induced cell death in vitro in rats. Furthermore, beta cell CART is upregulated in T2D patients and in diabetic rodent models as a consequence of hyperglycaemia. The aim of this study was to assess the impact of upregulated beta cell CART on islet hormone secretion and glucose homeostasis in a transgenic mouse model. To this end, mice with beta cell-specific overexpression of CART (CARTtg mice) were generated. CARTtg mice challenged by aging, high fat diet feeding or streptozotocin treatment were phenotyped with respect to in vivo and in vitro insulin and glucagon secretion, glucose homeostasis, and beta cell mass. In addition, the impact of adenoviral overexpression of CART on insulin secretion was studied in INS-1 832/13 cells. CARTtg mice had a normal metabolic phenotype under basal conditions. On the other hand, with age CARTtg mice displayed increased insulin secretion and improved glucose elimination, compared with age-matched WT mice. Furthermore, compared with WT controls, CARTtg mice had increased insulin secretion after feeding a high fat diet, as well as lower glucose levels and higher insulin secretion after streptozotocin treatment. Viral overexpression of CART in INS-1 832/13 cells resulted in increased glucose-stimulated insulin secretion. Together, these results imply that beta cell CART acts to increase insulin secretion when beta cell function is challenged. We propose that the increase in beta cell CART is part of a compensatory mechanisms trying to counteract the hyperglycaemia in T2D.

(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
keywords
Beta cell, CART, CART peptide, CARTPT, Cocaine- and amphetamine-regulated transcript, In vivo, INS-1, Islet, IVGTT, OGTT, T2D, Type 2 diabetes
in
Peptides
volume
151
article number
170747
publisher
Elsevier
external identifiers
  • scopus:85123599250
  • pmid:35065097
ISSN
0196-9781
DOI
10.1016/j.peptides.2022.170747
language
English
LU publication?
yes
id
dafc3841-4d9f-43b4-baea-d0ccd99c2209
date added to LUP
2022-02-18 15:37:46
date last changed
2024-04-23 02:05:46
@article{dafc3841-4d9f-43b4-baea-d0ccd99c2209,
  abstract     = {{<p>Impaired beta cell function and beta cell death are key features of type 2 diabetes (T2D). Cocaine- and amphetamine-regulated transcript (CART) is necessary for normal islet function in mice. CART increases glucose-stimulated insulin secretion in vivo in mice and in vitro in human islets and CART protects beta cells against glucotoxicity-induced cell death in vitro in rats. Furthermore, beta cell CART is upregulated in T2D patients and in diabetic rodent models as a consequence of hyperglycaemia. The aim of this study was to assess the impact of upregulated beta cell CART on islet hormone secretion and glucose homeostasis in a transgenic mouse model. To this end, mice with beta cell-specific overexpression of CART (CARTtg mice) were generated. CARTtg mice challenged by aging, high fat diet feeding or streptozotocin treatment were phenotyped with respect to in vivo and in vitro insulin and glucagon secretion, glucose homeostasis, and beta cell mass. In addition, the impact of adenoviral overexpression of CART on insulin secretion was studied in INS-1 832/13 cells. CARTtg mice had a normal metabolic phenotype under basal conditions. On the other hand, with age CARTtg mice displayed increased insulin secretion and improved glucose elimination, compared with age-matched WT mice. Furthermore, compared with WT controls, CARTtg mice had increased insulin secretion after feeding a high fat diet, as well as lower glucose levels and higher insulin secretion after streptozotocin treatment. Viral overexpression of CART in INS-1 832/13 cells resulted in increased glucose-stimulated insulin secretion. Together, these results imply that beta cell CART acts to increase insulin secretion when beta cell function is challenged. We propose that the increase in beta cell CART is part of a compensatory mechanisms trying to counteract the hyperglycaemia in T2D.</p>}},
  author       = {{Abels, Mia and Riva, Matteo and Shcherbina, Liliya and Fischer, Ann Helen Thorén and Banke, Elin and Degerman, Eva and Lindqvist, Andreas and Wierup, Nils}},
  issn         = {{0196-9781}},
  keywords     = {{Beta cell; CART; CART peptide; CARTPT; Cocaine- and amphetamine-regulated transcript; In vivo; INS-1; Islet; IVGTT; OGTT; T2D; Type 2 diabetes}},
  language     = {{eng}},
  month        = {{05}},
  publisher    = {{Elsevier}},
  series       = {{Peptides}},
  title        = {{Overexpressed beta cell CART increases insulin secretion in mouse models of insulin resistance and diabetes}},
  url          = {{http://dx.doi.org/10.1016/j.peptides.2022.170747}},
  doi          = {{10.1016/j.peptides.2022.170747}},
  volume       = {{151}},
  year         = {{2022}},
}