Journal article
Insulin and IGF-1 receptor autocrine loops are not required for Exendin-4 induced changes to pancreatic beta-cell bioenergetic parameters and metabolism in BRIN-BD11 cells
Peptides (New York, N.Y. : 1980), Vol.100, pp.140-149
02/2018
PMID: 29412813
Metrics
12 Record Views
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Abstract
Pharmacological long lasting Glucagon-like peptide-1 (GLP-1) analogues, such as Exendin-4, have become widely used diabetes therapies. Chronic GLP-1R stimulation has been linked to β-cell protection and these pro-survival actions of GLP-1 are dependent on the activation of the mammalian target of rapamycin (mTOR) leading to accumulation of Hypoxia inducible factor 1 alpha (HIF-1α). Recent studies from our lab indicate that prolonged GLP-1R stimulation promotes metabolic reprograming of β-cells towards a highly glycolytic phenotype and activation of the mTOR/HIF-1α pathway was required for this action. We hypothesised that GLP-1 induced metabolic changes depend on the activation of mTOR and HIF-1α, in a cascade that occurs after triggering of a potential Insulin-like growth factor 1 receptor (IGF-1R) or the Insulin receptor (IR) autocrine loops. Loss of function of these receptors, through the use of small interfering RNA, or neutralizing antibodies directed towards their products, was undertaken in conjunction with functional assays. Neither of these strategies mitigated the effect of GLP-1 on glucose uptake, protein expression or bioenergetic flux. Our data indicates that activation of IGF-1R and/or the IR autocrine loops resulting in β-cell protection and function, involve mechanisms independent to the enhanced metabolic effects resulting from sustained GLP-1R activation.
Details
- Title
- Insulin and IGF-1 receptor autocrine loops are not required for Exendin-4 induced changes to pancreatic beta-cell bioenergetic parameters and metabolism in BRIN-BD11 cells
- Creators
- Jordan Rowlands - Curtin UniversityVinicius Cruzat - Curtin UniversityRodrigo Carlessi - Curtin UniversityPhilip Newsholme - Curtin University
- Publication Details
- Peptides (New York, N.Y. : 1980), Vol.100, pp.140-149
- Publisher
- Elsevier
- Number of pages
- 10
- Identifiers
- 991013072491302368
- Copyright
- © 2017 Elsevier Inc. All rights reserved.
- Academic Unit
- Faculty of Health
- Language
- English
- Resource Type
- Journal article