Insulin alters nuclear factor-lambdaB and peroxisome proliferator-activated receptor-gamma protein expression induced by glycated bovine serum albumin in vascular smooth-muscle cells.
In both type 2 diabetes and insulin-resistance syndromes, hyperglycemia and advanced glycation end products (AGEs) activate the transcription factor nuclear factor-kappaB (NF-kappaB) through a mechanism that partly involves the generation of reactive oxygen species (ROS). The contribution of hyperinsulinemia in this sequence has not been completely elucidated. In this work we investigated the actions of insulin and PPAR-gamma on the stimulation by AGEs of NF-kappaB protein expression in cultured aortic vascular smooth-muscle cells (VSMCs) from non-insulin-dependent diabetic rats and nondiabetic rats. The expression of proteins was evaluated with the use of Western immunoblotting. Incubations (24 hours) of VSMCs with 10 to 100 microg/mL glycated bovine serum albumin (AGE- BSA) increased NF-kappaB protein expression in both models. PPAR-gamma protein expression was only enhanced at concentrations of 500 to 1000 microg/mL (AGE-BSA). In the presence of insulin (10-100 nmol/L), the stimulation of NF-kappaB protein expression by AGE-BSA (100 microg/mL) was decreased, whereas the expression of PPAR-gamma, protein was enhanced. 15-Deoxyprostaglandin J2, a direct activator of PPAR-gamma, decreased AGE-BSA-stimulated NF-kappaB expression. These findings suggest that insulin decreases the incidence of alterations in VSMCs induced by AGEs through the reduction of NF-kappaB and an increase in PPAR-gamma protein expression (as far as the model could be extrapolated to in vivo situations). These data may help justify current therapeutic approaches involving the use of insulin and PPAR-gamma agonists.
De Oliveira
Cristina
C
Laboratoire de Nutrition Humaine et Athérogénèse, Université Montpellier I.
Colette
Claude
C
Monnier
Louis
L
Descomps
Bernard
B
Pares-Herbute
Nuria
N
D000818:Animals; D002417:Cattle; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis*; D047495:PPAR gamma / Q000096:biosynthesis*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D000093423:Glycated Serum Albumin
C477819:15-deoxyprostaglandin J2; D017127:Glycation End Products, Advanced; D007328:Insulin; D016328:NF-kappa B; D047495:PPAR gamma; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D015230:Prostaglandin D2; D000093423:Glycated Serum Albumin