Early activation of the fatty acid metabolism pathway by chronic high glucose exposure in rat insulin secretory beta-cells.
Pancreatic beta-cells are responsible for insulin secretion that regulates blood glucose homeostasis. In the development of type II diabetes, a progressive impairment of insulin secretion by the pancreatic beta-cells occurs called beta-cell dysfunction or beta-cell failure. Chronic hyperglycemia has been shown being involved in beta-cell dysfunction, a phenomenon known as glucotoxicity. The molecular mechanisms underlying the impairment of insulin secretion by beta-cells induced by glucotoxicity are still not fully understood. In this work, quantitative proteomics was employed to identify early key players involved in beta-cell dysfunction induced by glucotoxicity. For this, the stable isotope labeling by amino acids in cell culture strategy was used on the slowly-growing rat beta-cell line INS-1E. We showed that the stable isotope labeling by amino acids in cell culture approach did not induce any detectable biological effects on these beta-cells, as measured at both the transcriptomic and proteomic levels. Proteins differentially expressed between control cells and cells submitted to chronic high glucose concentrations were identified and verified. The results obtained reinforce the link between glucotoxicity and lipogenesis and suggest that the fatty acid metabolism pathway may rapidly be stimulated in beta-cells submitted to chronic high glucose concentrations.
Couté
Yohann
Y
Biomedical Proteomics Research Group, Structural Biology and Bioinformatics Department, Centre Médical Universitaire, Geneva, Switzerland.
Brunner
Yannick
Y
Schvartz
Domitille
D
Hernandez
Céline
C
Masselot
Alexandre
A
Lisacek
Frédérique
F
Wollheim
Claes B
CB
Sanchez
Jean-Charles
JC
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D005227:Fatty Acids / Q000378:metabolism*; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism*; D020543:Proteome / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D013997:Time Factors
D005227:Fatty Acids; D007328:Insulin; D020543:Proteome; D005947:Glucose