RESUMEN
High concentrations of free fatty acids (FFAs) or lipopolysaccharide (LPS) could lead to ß-cell apoptosis and dysfunction, while low-grade elevation of FFAs or LPS, which are more common in people with type 2 diabetes mellitus (T2DM) or obesity, have no obvious toxic effect on ß-cells. Palmitate is a component closely related to metabolic disorders in FFAs. Recent studies have found that low-grade elevation of palmitate and LPS synergistically affects the sphingolipid signaling pathway by activating Toll-like receptor 4 (TLR4) and further enhances the expression of inflammatory cytokines in immune cells. Previous studies demonstrated that sphingolipids also played an important role in the occurrence and development of T2DM. This study aimed to investigate the synergistic effects of low-grade elevation of palmitate and LPS on viability, apoptosis and insulin secretion in the rat pancreatic ß-cell line INS-1 or islets and the role of sphingolipids in this process. We showed that low-grade elevation of palmitate or LPS alone did not affect the viability, apoptosis, glucose-stimulated insulin secretion (GSIS) or intracellular insulin content of INS-1 cells or islets, while the combination of the two synergistically inhibited cell viability, induced apoptosis and decreased basal insulin secretion in INS-1 cells or islets. Treatment with palmitate and LPS markedly upregulated TLR4 protein expression and downregulated neutral ceramidase (NCDase) activity and protein expression. Additionally, low-grade elevation of palmitate and LPS synergistically induced a significant increase in ceramide and a decrease in sphingosine-1-phosphate. Blocking TLR4 signaling or overexpressing NCDase remarkably attenuated INS-1 cell injury induced by the combination of palmitate and LPS. However, inhibition of ceramide synthase did not ameliorate injury induced by palmitate and LPS. Overall, we show for the first time that low-grade elevation of palmitate and LPS synergistically induced ß-cell damage by activating TLR4 signaling, inhibiting NCDase activity, and further modulating sphingolipid metabolism, which was different from a high concentration of palmitate-induced ß-cell injury by promoting ceramide synthesis.
Asunto(s)
Células Secretoras de Insulina/citología , Lipopolisacáridos/efectos adversos , Ceramidasa Neutra/metabolismo , Palmitatos/efectos adversos , Receptor Toll-Like 4/metabolismo , Animales , Apoptosis , Línea Celular , Sinergismo Farmacológico , Regulación de la Expresión Génica/efectos de los fármacos , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , Esfingolípidos/metabolismoRESUMEN
The EST sequence of goose (Anser cygnoides) Stearoyl-CoA desaturase 1(SCD-1) was obtained from a subtractive cDNA library. To further investigate the role of SCD-1 in lipid metabolism in geese, 5'-RACE and 3'-RACE were carried out in this study to obtain the complete cDNA sequence of goose SCD-1, which contained a 29-bp 5' UTR, a 1074-bp open reading frame (ORF) encoding 357 amino acids, and a 125-bp 3' UTR. The expression of SCD-1 was measured in several tissues, and the effects of overfeeding on the expression of SCD-1 were studied. The results of real time RT-PCR demonstrated that, compared to the brain, goose SCD-1 mRNA was more abundant in the liver. Overfeeding markedly increased the mRNA expression of SCD-1 in the liver of Sichuan White and Landes geese, and gene expression was markedly higher in the Sichuan White goose than in the landes goose. The mRNA abundance of SCD-1 in the liver had significant positive correlations with triacylglycerol (TG) content in liver lipids and in the levels of plasma insulin and very low-density lipoproteins (VLDL) levels in Sichuan white geese. However, the mRNA abundance of SCD-1 in the livers of Landes geese had only significant positive correlations with the TG content in liver lipids. In conclusion, SCD-1 is not only critical for hepatic steatosis in geese but is also important for the difference in lipid deposition in the livers of the two breeds.
Asunto(s)
Ingestión de Alimentos , Gansos/metabolismo , Hígado/enzimología , Hipernutrición , Estearoil-CoA Desaturasa/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Células Cultivadas , Clonación Molecular , Etiquetas de Secuencia Expresada , Hígado Graso/genética , Hígado Graso/metabolismo , Gansos/anatomía & histología , Gansos/genética , Hepatocitos/citología , Hepatocitos/metabolismo , Metabolismo de los Lípidos/genética , Lipoproteínas VLDL/genética , Lipoproteínas VLDL/metabolismo , Masculino , Datos de Secuencia Molecular , Filogenia , Alineación de Secuencia , Estearoil-CoA Desaturasa/clasificación , Estearoil-CoA Desaturasa/genética , Triglicéridos/genética , Triglicéridos/metabolismoRESUMEN
PURPOSE: The purpose of this paper is to investigate logistics activities in Singapore hospitals. It defines various types of activities handled by a logistics division. Inventory management policy and the use of information and communication technologies (ICT) for logistics purposes are also discussed. The study identifies the nature of strategic alliances in Singapore's health care industry. DESIGN/METHODOLOGY/APPROACH: This study was conducted by utilizing a framework for data collection, pre-testing the questionnaire and conducting interviews. Various relevant literature was reviewed to design the questionnaire. FINDINGS: This study finds that logistics division carry out many related activities and some of them also provide engineering services. The hospitals make use of ICT. The hospitals are clustered under various groups to minimize the cost of operation, including the logistics related costs. However, hospitals do not see alliances with suppliers as a strategic option; rather they focus on outsourcing of logistics services. The findings also show that Singapore hospitals have a good stocking policy for both medical and non-medical items so that changes in patient mix can be easily handled. ORIGINALITY/VALUE: Singapore is continuously improving its health care industry and therefore, the findings will help hospitals in other regions to adopt some of the practices, like concentrating on local vendors, outsourcing, clustering, and maximum use of information technology as competitive factors that can improve the service and reduce the cost of operation. The paper suggests motivators and barriers to the use of ICT in logistics in the health care industry.