Advanced

Enhanced beta cell function and anti-inflammatory effect after chronic treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin in an advanced-aged diet-induced obesity mouse model.

Omar, Bilal LU ; Vikman, Jenny LU ; Sörhede Winzell, Maria LU ; Voss, Ulrikke LU ; Ekblad, Eva LU ; Foley, J E and Ahrén, Bo LU (2013) In Diabetologia 56(8). p.1752-1760
Abstract
AIMS/HYPOTHESIS: Studies have shown that dipeptidyl peptidase-4 (DPP4) inhibitors stimulate insulin secretion and increase beta cell mass in rodents. However, in these models hyperglycaemia has been induced early on in life and the treatment periods have been short. To explore the long-term effects of DPP4 inhibition on insulin secretion and beta cell mass, we have generated a high-fat diet (HFD)-induced-obesity model in mice of advanced age (10 months old). METHODS: After 1 month of HFD alone, the mice were given the DPP4 inhibitor vildagliptin for a further 11 months. At multiple time points throughout the study, OGTTs were performed and beta cell area and long-term survival were evaluated. RESULTS: Beta cell function and glucose... (More)
AIMS/HYPOTHESIS: Studies have shown that dipeptidyl peptidase-4 (DPP4) inhibitors stimulate insulin secretion and increase beta cell mass in rodents. However, in these models hyperglycaemia has been induced early on in life and the treatment periods have been short. To explore the long-term effects of DPP4 inhibition on insulin secretion and beta cell mass, we have generated a high-fat diet (HFD)-induced-obesity model in mice of advanced age (10 months old). METHODS: After 1 month of HFD alone, the mice were given the DPP4 inhibitor vildagliptin for a further 11 months. At multiple time points throughout the study, OGTTs were performed and beta cell area and long-term survival were evaluated. RESULTS: Beta cell function and glucose tolerance were significantly improved by vildagliptin with both diets. In contrast, in spite of the long treatment period, beta cell area was not significantly different between vildagliptin-treated mice and controls. Mice of advanced age chronically fed an HFD displayed clear and extensive pancreatic inflammation and peri-insulitis, mainly formed by CD3-positive T cells, which were completely prevented by vildagliptin treatment. Chronic vildagliptin treatment also improved survival rates for HFD-fed mice. CONCLUSIONS/INTERPRETATION: In a unique advanced-aged HFD-induced-obesity mouse model, insulin secretion was improved and the extensive peri-insulitis prevented by chronic DPP4 inhibition. The improved survival rates for obese mice chronically treated with vildagliptin suggest that chronic DPP4 inhibition potentially results in additional quality-adjusted life-years for individuals with type 2 diabetes, which is the primary goal of any diabetes therapy. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetologia
volume
56
issue
8
pages
1752 - 1760
publisher
Springer
external identifiers
  • wos:000321285400011
  • pmid:23636640
  • scopus:84879914429
ISSN
1432-0428
DOI
10.1007/s00125-013-2927-8
language
English
LU publication?
yes
id
5a781d47-1ef2-4816-81cb-5f7cdd4eb293 (old id 3805031)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23636640?dopt=Abstract
date added to LUP
2013-06-04 21:30:58
date last changed
2019-01-20 03:12:53
@article{5a781d47-1ef2-4816-81cb-5f7cdd4eb293,
  abstract     = {AIMS/HYPOTHESIS: Studies have shown that dipeptidyl peptidase-4 (DPP4) inhibitors stimulate insulin secretion and increase beta cell mass in rodents. However, in these models hyperglycaemia has been induced early on in life and the treatment periods have been short. To explore the long-term effects of DPP4 inhibition on insulin secretion and beta cell mass, we have generated a high-fat diet (HFD)-induced-obesity model in mice of advanced age (10 months old). METHODS: After 1 month of HFD alone, the mice were given the DPP4 inhibitor vildagliptin for a further 11 months. At multiple time points throughout the study, OGTTs were performed and beta cell area and long-term survival were evaluated. RESULTS: Beta cell function and glucose tolerance were significantly improved by vildagliptin with both diets. In contrast, in spite of the long treatment period, beta cell area was not significantly different between vildagliptin-treated mice and controls. Mice of advanced age chronically fed an HFD displayed clear and extensive pancreatic inflammation and peri-insulitis, mainly formed by CD3-positive T cells, which were completely prevented by vildagliptin treatment. Chronic vildagliptin treatment also improved survival rates for HFD-fed mice. CONCLUSIONS/INTERPRETATION: In a unique advanced-aged HFD-induced-obesity mouse model, insulin secretion was improved and the extensive peri-insulitis prevented by chronic DPP4 inhibition. The improved survival rates for obese mice chronically treated with vildagliptin suggest that chronic DPP4 inhibition potentially results in additional quality-adjusted life-years for individuals with type 2 diabetes, which is the primary goal of any diabetes therapy.},
  author       = {Omar, Bilal and Vikman, Jenny and Sörhede Winzell, Maria and Voss, Ulrikke and Ekblad, Eva and Foley, J E and Ahrén, Bo},
  issn         = {1432-0428},
  language     = {eng},
  number       = {8},
  pages        = {1752--1760},
  publisher    = {Springer},
  series       = {Diabetologia},
  title        = {Enhanced beta cell function and anti-inflammatory effect after chronic treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin in an advanced-aged diet-induced obesity mouse model.},
  url          = {http://dx.doi.org/10.1007/s00125-013-2927-8},
  volume       = {56},
  year         = {2013},
}