High glucose concentration in T1D patients modulates apoptotic protein expression: down regulation of BAX and FAS and up regulation of XIAP.
Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by a progressive destruction of pancreatic β cells. It has been reported that patients with autoimmune diseases exhibit decreased expression of caspase 3 and other pro-apoptotic markers in peripheral blood mononuclear cells (PBMC).


OBJECTIVE
To estimate the expression of apoptosis markers in PBMC from T1D patients cultured with high glucose concentration.


RESULTS
At 11 mM of glucose, the pro-apoptotic gene fas showed a 7-fold decreased expression in the T1D group compared to controls, while bax showed a 50-fold decreased expression (medians 0.14 and 0.02, respectively, considering patients as 1). At 44 mM of glucose, there is a decreased expression of the same genes, but less abrupt (medians 0.75 and 0.47). Only the anti-apoptotic gene xiap showed a 2-fold increased expression at 11 mM of glucose (median 2.3). Regarding the clinical history, no relationships were observed with age of diagnosis, ketoacidosis, glucose at debut or GAD-65 and IA-2 titles.


CONCLUSIONS
We can conclude that the apoptotic mechanisms in PBMC of T1D patients under high glucose conditions are altered, and this is proved by the decreased expression of the pro-apoptotic genes fas and bax and by the increased expression of the anti-apoptotic gene xiap.
Laboratorio de Genómica Nutricional, Departamento de Nutrición, Facultad de Medicina, Universidad de Chile, Chile.
Elizabeth
E
Valencia
Ethel
E
Codner
Francisca
F
Salas-Pérez
Carolina
C
Pizarro
Elena
E
Carrasco P
Miguel
M
Arredondo
Francisco
F
Pérez-Bravo
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics* / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism
C494826:BAX protein, human; D015415:Biomarkers; C491901:FAS protein, human; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D005947:Glucose