RESUMO
A number of patients with hyperlipidemia are prescribed 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors that are concomitantly used along with the treatment of diabetes mellitus. The effects of atorvastatin and pravastatin on insulin-induced glucose uptake and the related signal transduction in 3T3L1 adipocytes were studied. 3T3L1 fibroblasts were differentiated into adipocytes, pretreated with atorvastatin or pravastatin, and then exposed to insulin. Glucose uptake and the amount of insulin signal proteins were measured. Atorvastatin significantly decreased insulin-stimulated 2-deoxyglucose uptake in 3T3L1 adipocytes associated with the prevention of translocation of GLUT4 into the plasma membrane. The amounts of Rab4 and RhoA that required lipid modification with farnesyl or geranylgeranyl pyrophosphate, in the membrane fraction were decreased by atorvastatin. Insulin-induced tyrosine phosphorylation of IRS-1 and serine/threonine phosphorylation of Akt were reduced by atorvastatin. Pravastatin did not modify these insulin-induced changes in the signal transduction. Inhibitors of the RhoA/Rho kinase system, C3 and Y27632, as well as atorvastatin reduced insulin-induced changes in signal transduction. Atorvastatin and pravastatin did not affect messenger RNA expression, protein level, and tyrosine phosphorylation of insulin receptors. In conclusion, hydrophobic atorvastatin decreases the glucose uptake by 3T3L1 adipocytes since it can enter the cell and prevents lipid modification of some proteins that are involved in the insulin signal transduction process.
Assuntos
Adipócitos/efeitos dos fármacos , Glucose/metabolismo , Ácidos Heptanoicos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Insulina/metabolismo , Pravastatina/farmacologia , Pirróis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células 3T3-L1 , ADP Ribose Transferases/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adipócitos/enzimologia , Adipócitos/metabolismo , Amidas/farmacologia , Animais , Atorvastatina , Toxinas Botulínicas/farmacologia , Relação Dose-Resposta a Droga , Transportador de Glucose Tipo 4/metabolismo , Proteínas Substratos do Receptor de Insulina , Camundongos , Fosforilação , Fosfatos de Poli-Isoprenil/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Prenilação de Proteína , Transporte Proteico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas/farmacologia , RNA Mensageiro/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Proteínas rab4 de Ligação ao GTP/metabolismo , Proteínas rho de Ligação ao GTP/antagonistas & inibidores , Proteínas rho de Ligação ao GTP/metabolismo , Quinases Associadas a rho/antagonistas & inibidores , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTPRESUMO
Contraction of skeletal muscle generates pressure stimuli to intramuscular tissues. However, the effects of pressure stimuli, other than those created by electricity or nerve impulse, on physiological and biochemical responses in skeletal muscles are unknown. The purpose of this study is to examine the effects of a pure pressure stimulus on metabolic responses in a skeletal muscle cell line. Atmospheric pressure was applied to L6 myoblasts using an original apparatus. Succinate dehydrogenase (SDH) activity was evaluated by colorimetric assay using tetrazolium monosodium salt. The amounts of 2-deoxy-[(3)H]glucose uptake and lactate release were measured. SDH activity was 2.6- to 2.9-fold higher in pressurized L6 cells than in nonpressurized L6 cells (P < 0.01), and 2-deoxy-[(3)H]glucose uptake was 2.2-fold higher (P < 0.001). In addition, the amount of released lactate decreased from 6.8 to 3.7 mumol/dish when pressure was applied (P < 0.001). In contrast, the intracellular lactate contents of the pressurized cells were higher than those of nonpressurized cells (P < 0.01). However, the total amount of released lactate and intracellular lactate was lower in the pressurized cells than in nonpressurized cells. These findings demonstrate that a pure pressure stimulus enhances aerobic metabolism in L6 skeletal muscle cells and raise the possibility that elevated intramuscular pressure during muscle activity may be an important factor in stimulating oxidative metabolic responses in skeletal muscles.
Assuntos
Pressão Atmosférica , Mioblastos/enzimologia , Succinato Desidrogenase/metabolismo , Animais , Linhagem Celular , Cicloeximida/farmacologia , Gadolínio/farmacologia , Glucose/metabolismo , Ácido Láctico/metabolismo , Mioblastos/metabolismo , Consumo de Oxigênio , RatosRESUMO
Procalcitonin (PCT), the precursor protein of calcitonin (CT), has been considered recently as a significant indicator of bacterial infection and sepsis. However, the major source of PCT in sepsis remains unclear. The hypothalamic-pituitary-adrenal axis is activated during sepsis. Moreover, immunoreactive CT (iCT) can be detected in the pituitary. Therefore, we examined the effects of lipopolysaccharide (LPS) administration on CT mRNA expression in the pituitary. After administration of LPS, CT mRNA expression in the pituitary was increased significantly. The increase of CT mRNA was associated with significant elevations of the iCT levels in the serum. These results imply that the pituitary is one of the sources of the serum PCT during sepsis.
Assuntos
Calcitonina/genética , Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Hipófise/metabolismo , Hormônio Adrenocorticotrópico/sangue , Animais , Northern Blotting , Calcitonina/sangue , Interleucina-1/genética , Interleucina-6/genética , Cinética , Masculino , Hipófise/química , RNA Mensageiro/análise , Ratos , Ratos Wistar , Receptores da Calcitonina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sepse/metabolismo , Fator de Necrose Tumoral alfa/genéticaRESUMO
We examined the effects of troglitazone, one of thiazolidinedione derivatives on human basophilic leukemia cell line KU812. Troglitazone caused the suppression of cell growth, which was suggested to result from the decrease in cyclin E and the hyperphosphorylated form of retinoblastoma tumor suppressor gene product (pRb). In addition, troglitazone caused a decrease in histamine secretion due to the reduced expression of histidine decarboxylase mRNA. Peroxisome proliferator-activated receptor (PPAR)-gamma mRNA was undetectable by reverse transcription-polymerase chain reaction (RT-PCR) in KU812 cells. These findings suggested that troglitazone suppressed cell growth and histamine synthesis independently of PPARgamma.
