Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Exendin-4 protects pancreatic BTC-6 cells against metabolic stress: a proteomic study (#883)

Dhanya Madhu 1 , Maha Hammad 1 , Sina kavalakatt 1 , Abdelkrim Khadir 1 , Ali Tiss 1
  1. Dasman diabetes Institute, Kuwait, KUWAIT

Background and objectives:  Lipotoxicity is an important factor in the pathogenesis of type 2 diabetes resulting in defective β-cell proliferation and increased apoptosis. Increase in glucagon-like peptide-1 (GLP-1) activity has recently emerged for the treatment of type 2 diabetes (T2D) by enhancing the glycemic control and helping in decreasing body weight of most patients. Recent studies have suggested beneficial effects of these peptides on insulin-responsive tissues such as adipose tissue, muscles and liver aside with pancreatic β-cells.  We investigated here the potential beneficial effects of a GLP-1 mimetic on mouse pancreatic cells under stressing levels of palmitic acid (PA).

Methods:  Using mouse pancreatic cell line (BTC-6), we investigated the effect of a GLP1 mimetic (Exendin-4) on the protein expression pattern using Mass Spectrometry approaches (LC-MS/MS Orbitrap system and label-free quantification) in the presence of stressing amounts of PA. We also investigated the impact of Exendin-4 on MAPKs using RT-PCR and Western blot. Cell viability assay and lipid droplet accumulation assessment were also performed.

Results: We showed that ERK MAP-Kinase phosphorylation was highly increased by Exendin-4 both in presence and absence of PA. Furthermore, cell viability assays have shown that Exendin-4 significantly alleviated the PA-induced cell death. This was further confirmed with proteomics analysis where various cellular functions were improved in presence of Exendin-4, including cell growth, cellular assembly and organisation. Moreover, proteomics analysis highlighted a panel of interconnected heat shock proteins (HSP) that have been modulated by Exendin-4. This was further confirmed by Western blot where the heat-shock inducible HSP72 was significantly increased by PA and attenuated in presence Exendin-4.

Conclusion: Our results suggest that GLP-1 mimetics alleviate the lipotoxicity-related cellular stress in pancreatic cells and enhance heat shock response thus restoring normal cellular homeostasis.