BACKGROUND Colorectal cancer(CRC)is a worldwide problem,which has been associated with changes in diet and lifestyle pattern.As a result of colonic fermentation of dietary fibres,short chain free fatty acids are gener...BACKGROUND Colorectal cancer(CRC)is a worldwide problem,which has been associated with changes in diet and lifestyle pattern.As a result of colonic fermentation of dietary fibres,short chain free fatty acids are generated which activate free fatty acid receptors(FFAR)2 and 3.FFAR2 and FFAR3 genes are abundantly expressed in colonic epithelium and play an important role in the metabolic homeostasis of colonic epithelial cells.Earlier studies point to the involvement of FFAR2 in colorectal carcinogenesis.AIM To understand the role of short chain FFARs in CRC.METHODS Transcriptome analysis console software was used to analyse microarray data from CRC patients and cell lines.We employed short-hairpin RNA mediated down regulation of FFAR2 and FFAR3 genes,which was validated using quantitative real time polymerase chain reaction.Assays for glucose uptake and cyclic adenosine monophosphate(cAMP)generation was done along with immunofluorescence studies to study the effects of FFAR2/FFAR3 knockdown.For measuring cell proliferation,we employed real time electrical impedancebased assay available from xCELLigence.RESULTS Microarray data analysis of CRC patient samples showed a significant down regulation of FFAR2 gene expression.This prompted us to study the FFAR2 in CRC.Since,FFAR3 shares significant structural and functional homology with FFAR2,we knocked down both these receptors in CRC cell line HCT 116.These modified cell lines exhibited higher proliferation rate and were found to have increased glucose uptake as well as increased level of glucose transporter 1.Since,FFAR2 and FFAR3 signal through G protein subunit(Gαi),knockdown of these receptors was associated with increased cAMP.Inhibition of protein kinase A(PKA)did not alter the growth and proliferation of these cells indicating a mechanism independent of cAMP/PKA pathway.CONCLUSION Our results suggest role of FFAR2/FFAR3 genes in increased proliferation of colon cancer cells via enhanced glucose uptake and exclude the role of PKA mediated cAMP signalling.Alternate pathways could be involved that would ultimately result in increased cell proliferation as a result of down regulated FFAR2/FFAR3 genes.This study paves the way to understand the mechanism of action of short chain FFARs in CRC.展开更多
BACKGROUND: It has been reported that high-dose salicylates improve free fatty acids (FFAs)-induced insulin resistance and beta-cell dysfunction in vitro, but the mechanism remains uncertain. In insulin-resistant rats...BACKGROUND: It has been reported that high-dose salicylates improve free fatty acids (FFAs)-induced insulin resistance and beta-cell dysfunction in vitro, but the mechanism remains uncertain. In insulin-resistant rats, we found that the supplementation of sodium salicylate is associated with a reduction of plasma malondialdehyde (MDA), a marker of oxidative stress. Few studies have investigated the effects of salicylates on oxidative stress levels in insulin-resistant animal models. This study aimed to assess the effect of sodium salicylate on insulin sensitivity and to explore the potential mechanism by which it improves hepatic and peripheral insulin resistance. METHODS: Intralipid+heparin (IH), saline (SAL), or intralipid+heparin+sodium salicylate (IHS) were separately infused for 7 hours in normal Wistar rats. During the last 2 hours of the infusion, hyperinsulinemic-euglycemic clamping was 3 performed with [6-(3)H] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassay. MDA levels and glutathione peroxidase (GSH-PX) activity in the liver and skeletal muscle were measured with colorimetric kits. RESULTS: Compared with infusion of SAL, IH infusion increased hepatic glucose production (HGP), and decreased glucose utilization (GU) (P<0.05). The elevation of plasma free fatty acids increased the MDA levels and decreased the GSH-PX activity in the liver and muscle (P<0.01). Sodium salicylate treatment decreased HGP, elevated GU (P<0.05), reduced MDA content by 60% (P<0.01), and increased the GSH-PX activity by 35% (P<0.05). CONCLUSIONS: Short-term elevation of fatty acids induces insulin resistance by enhancing oxidative stress levels in the liver and muscle. The administration of the anti-inflammatory drug sodium salicylate reduces the degree of oxidative stress, therefore improving hepatic and peripheral insulin resistance. IKK-beta and NF-kappa B provide potential pathogenic links to oxidative stress.展开更多
Non edible oil sources have the potential to lower the cost of biodiesel. However, they usually contain significant high amounts of free fatty acids (FFA) that make them inadequate for direct base catalyzed transester...Non edible oil sources have the potential to lower the cost of biodiesel. However, they usually contain significant high amounts of free fatty acids (FFA) that make them inadequate for direct base catalyzed transesterification reaction (where the FFA content should be lower than 3%). The present work reviews chemical re-esterification as a possible method for the pre-treatment of high FFA feedstock for biodiesel production. The effects of temperature, amount of glycerol, type and amount of catalyst have been discussed. Chemical re-esterification lowers FFA to acceptable levels for transesterification at the same time utilizing the glycerol by product from the same process. Further researches have been proposed as a way forward to improve the process kinetics and optimization so as to make it more economical.展开更多
Objective: To investigate the correlation of serum free fatty acid content with glucolipid metabolism, microinflammation and oxidative stress state in patients with type 2 diabetes mellitus. Methods: A total of 189 pa...Objective: To investigate the correlation of serum free fatty acid content with glucolipid metabolism, microinflammation and oxidative stress state in patients with type 2 diabetes mellitus. Methods: A total of 189 patients with type 2 diabetes mellitus who were treated in this hospital between August 2015 and February 2018 were chosen as type 2 diabetes mellitus group, and 100 healthy subjects who received physical examination in this hospital during the same period were chosen as the normal control group. The differences in serum levels of FFA, glucolipid metabolism indexes, microinflammation indexes and oxidative stress indexes were compared between the two groups of subjects, and correlation analysis was adopted to judge the inner link of serum FFA content with glucolipid metabolism, microinflammation and oxidative stress state in patients with type 2 diabetes mellitus. Results: Serum FFA content of type 2 diabetes mellitus group was higher than that of control group;serum glucolipid metabolism indexes FPG, 2hPG, TC and LDL-C levels were higher than those of normal control group whereas HDL-C level was lower than that of control group;serum microinflammation indexes IL-1β, IL-6, IL-10, IL-15 and TNF-α contents were higher than those of control group;serum oxidative stress indexes GSH-Px and SOD contents were lower than those of control group whereas ROS and MDA contents were higher than those of control group. Pearson test showed that the serum FFA content of patients with type 2 diabetes mellitus was directly correlated with the contents of glucolipid metabolism, microinflammation and oxidative stress indexes. Conclusion: Serum FFA content significantly increases in patients with type 2 diabetes mellitus, and the specific content was directly correlated with glycolipid metabolism, microinflammation, oxidative stress and other illness indexes.展开更多
Objective Obesity-induced kidney injury contributes to the development of diabetic nephropathy(DN).Here,we identified the functions of ubiquitin-specific peptidase 19(USP19)in HK-2 cells exposed to a combination of hi...Objective Obesity-induced kidney injury contributes to the development of diabetic nephropathy(DN).Here,we identified the functions of ubiquitin-specific peptidase 19(USP19)in HK-2 cells exposed to a combination of high glucose(HG)and free fatty acid(FFA)and determined its association with TGF-beta-activated kinase 1(TAK1).Methods HK-2 cells were exposed to a combination of HG and FFA.USP19 mRNA expression was detected by quantitative RT-PCR(qRT-PCR),and protein analysis was performed by immunoblotting(IB).Cell growth was assessed by Cell Counting Kit-8(CCK-8)viability and 5-ethynyl-2′-deoxyuridine(EdU)proliferation assays.Cell cycle distribution and apoptosis were detected by flow cytometry.The USP19/TAK1 interaction and ubiquitinated TAK1 levels were assayed by coimmunoprecipitation(Co-IP)assays and IB.Results In HG+FFA-challenged HK-2 cells,USP19 was highly expressed.USP19 knockdown attenuated HG+FFA-triggered growth inhibition and apoptosis promotion in HK-2 cells.Moreover,USP19 knockdown alleviated HG+FFA-mediated PTEN-induced putative kinase 1(PINK1)/Parkin pathway inactivation and increased mitochondrial reactive oxygen species(ROS)generation in HK-2 cells.Mechanistically,USP19 stabilized the TAK1 protein through deubiquitination.Importantly,increased TAK1 expression reversed the USP19 knockdown-mediated phenotypic changes and PINK1/Parkin pathway activation in HG+FFA-challenged HK-2 cells.Conclusion The findings revealed that USP19 plays a crucial role in promoting HK-2 cell dysfunction induced by combined stimulation with HG and FFAs by stabilizing TAK1,providing a potential therapeutic strategy for combating DN.展开更多
BACKGROUND: Much evidence demonstrates that elevated free fatty acids (FFAs) are associated with insulin resistance. However, it is not clear whether different FFAs can cause different degrees of peripheral insulin re...BACKGROUND: Much evidence demonstrates that elevated free fatty acids (FFAs) are associated with insulin resistance. However, it is not clear whether different FFAs can cause different degrees of peripheral insulin resistance. This study aimed to investigate the effects of short-term elevation of FFAs on hepatic and peripheral insulin action, and determine whether FFAs with different degrees of saturation have differential effects on hepatic insulin resistance. METHODS: Intralipid+heparin (IH, polyunsaturated fatty acids), oleate (OLE), lard oil+heparin (LOH), and saline (SAL) were separately infused intravenously for 7 hours in normal Wistar rats. During the last 2 hours of the fat/saline infusion, a hyperinsulinemic-euglycemic clamping was performed with [6-H-3] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassays. Plasma FFAs were measured using a colorimetric method. RESULTS: Compared with infusion of SAL, plasma FFA levels were significantly elevated by infusions of IH, OLE, and LOH (P<0.001). All three fat infusions caused remarkably higher hepatic glucose production (HGP) than SAL (P<0.001). OLE and LOH infusions induced much higher HGP than IH (P<0.01). Glucose utilization (GU) was decreased with all three fat infusions relative to SAL (P<0.001), but GU did not differ among the three types of fat infusions. CONCLUSIONS: Short-term elevation of FFAs can induce hepatic and peripheral insulin resistance. Polyunsaturated fatty acids induced less hepatic insulin resistance than monounsaturated or saturated fatty acids. However, IH, OLE, and LOH infusions induced similar peripheral insulin resistance.展开更多
s To investigate the effects of glucose and free fatty acids (FFAs) on the proliferation and cell cycle of human vascular endothelial cells in vitro , and to examine whether the combined presence of elevated FFAs ...s To investigate the effects of glucose and free fatty acids (FFAs) on the proliferation and cell cycle of human vascular endothelial cells in vitro , and to examine whether the combined presence of elevated FFAs and glucose may cross amplify their individual injurious effects Methods Cultured human vascular endothelial cells (ECV304) were incubated with various concentrations of glucose and/or FFAs (palmitate and/or oleate) for 24-96 h Morphologic alterations were observed using a phase contrast microscope and an electron microscope Inhibition of proliferation was measured by a colorimetric 3 [4, 5 dimethyl thiazol 2 yl] 2, 5 diphenyltetrazolium bromide (MTT) assay Cell viability was determined using trypan blue exclusion Distribution of cells along phases of the cell cycle was analyzed by flow cytometry Results Glucose 15 or 30 mmol/L, palmitate (PA) 0 25 or 0 5 mmol/L, and oleate (OA) 0 5 mmol/L inhibited proliferation and accelerated death of endothelial cells in a dose and time dependent manner After treatment with elevated glucose and/or FFAs, the G 0/G 1 phase cells increased, whereas S phase cells decreased, suggesting that high glucose and/or FFAs mainly arrested endothelial cells at G 0/G 1 phase The inhibitive rates of proliferation and population of dead cells in endothelial cells incubated with glucose plus FFAs (glucose 30 mmol/L+PA 0 25 mmol/L, glucose 30 mmol/L+OA 0 5 mmol/L, glucose 30 mmol/L+PA 0 25 mmol/L+OA 0 5 mmol/L) increased more markedly than those treated with high glucose or FFAs (PA and/or OA) alone Conclusion Both high ambient glucose and FFAs can inhibit proliferation and accelerate death of endothelial cells in vitro These changes were cross amplified in the combined presence of high levels of glucose and FFAs展开更多
ResearchGate is a world wide web for scientists and researchers to share papers,ask and answer questions,and find collaborators.As one of the more than 15 million members,the author uploads research output and reads a...ResearchGate is a world wide web for scientists and researchers to share papers,ask and answer questions,and find collaborators.As one of the more than 15 million members,the author uploads research output and reads and responds to some of the questions raised,which are related to type 2 diabetes.In that way,he noticed a serious gap of knowledge of this disease among medical professionals over recent decades.The main aim of the current study is to remedy this situation through providing a comprehensive review on recent developments in biochemistry and molecular biology,which can be helpful for the scientific understanding of the molecular nature of type 2 diabetes.To fill up the shortcomings in the curricula of medical education,and to familiarize the medical community with a new concept of the onset of type 2 diabetes,items are discussed like:Insulin resistance,glucose effectiveness,insulin sensitivity,cell membranes,membrane flexibility,unsaturation index(UI;number of carboncarbon double bonds per 100 acyl chains of membrane phospholipids),slowdown principle,effects of temperature acclimation on phospholipid membrane composition,free fatty acids,energy transport,onset of type 2 diabetes,metformin,and exercise.Based on the reviewed data,a new model is presented with proposed steps in the development of type 2 diabetes,a disease arising as a result of a hypothetical hereditary anomaly,which causes hyperthermia in and around the mitochondria.Hyperthermia is counterbalanced by the slow-down principle,which lowers the amount of carbon-carbon double bonds of membrane phospholipid acyl chains.The accompanying reduction in the UI lowers membrane flexibility,promotes a redistribution of the lateral pressure in cell membranes,and thereby reduces the glucose transporter protein pore diameter of the transmembrane glucose transport channel of all Class I GLUT proteins.These events will set up a reduction in transmembrane glucose transport.So,a new blood glucose regulation system,effective in type 2 diabetes and its prediabetic phase,is based on variations in the acyl composition of phospholipids and operates independent of changes in insulin and glucose concentration.UI assessment is currently arising as a promising analytical technology for a membrane flexibility analysis.An increase in mitochondrial heat production plays a pivotal role in the existence of this regulation system.展开更多
文摘BACKGROUND Colorectal cancer(CRC)is a worldwide problem,which has been associated with changes in diet and lifestyle pattern.As a result of colonic fermentation of dietary fibres,short chain free fatty acids are generated which activate free fatty acid receptors(FFAR)2 and 3.FFAR2 and FFAR3 genes are abundantly expressed in colonic epithelium and play an important role in the metabolic homeostasis of colonic epithelial cells.Earlier studies point to the involvement of FFAR2 in colorectal carcinogenesis.AIM To understand the role of short chain FFARs in CRC.METHODS Transcriptome analysis console software was used to analyse microarray data from CRC patients and cell lines.We employed short-hairpin RNA mediated down regulation of FFAR2 and FFAR3 genes,which was validated using quantitative real time polymerase chain reaction.Assays for glucose uptake and cyclic adenosine monophosphate(cAMP)generation was done along with immunofluorescence studies to study the effects of FFAR2/FFAR3 knockdown.For measuring cell proliferation,we employed real time electrical impedancebased assay available from xCELLigence.RESULTS Microarray data analysis of CRC patient samples showed a significant down regulation of FFAR2 gene expression.This prompted us to study the FFAR2 in CRC.Since,FFAR3 shares significant structural and functional homology with FFAR2,we knocked down both these receptors in CRC cell line HCT 116.These modified cell lines exhibited higher proliferation rate and were found to have increased glucose uptake as well as increased level of glucose transporter 1.Since,FFAR2 and FFAR3 signal through G protein subunit(Gαi),knockdown of these receptors was associated with increased cAMP.Inhibition of protein kinase A(PKA)did not alter the growth and proliferation of these cells indicating a mechanism independent of cAMP/PKA pathway.CONCLUSION Our results suggest role of FFAR2/FFAR3 genes in increased proliferation of colon cancer cells via enhanced glucose uptake and exclude the role of PKA mediated cAMP signalling.Alternate pathways could be involved that would ultimately result in increased cell proliferation as a result of down regulated FFAR2/FFAR3 genes.This study paves the way to understand the mechanism of action of short chain FFARs in CRC.
基金supported by a grant from the Bureau of Education of Liaoning Province,China (No.20060999)
文摘BACKGROUND: It has been reported that high-dose salicylates improve free fatty acids (FFAs)-induced insulin resistance and beta-cell dysfunction in vitro, but the mechanism remains uncertain. In insulin-resistant rats, we found that the supplementation of sodium salicylate is associated with a reduction of plasma malondialdehyde (MDA), a marker of oxidative stress. Few studies have investigated the effects of salicylates on oxidative stress levels in insulin-resistant animal models. This study aimed to assess the effect of sodium salicylate on insulin sensitivity and to explore the potential mechanism by which it improves hepatic and peripheral insulin resistance. METHODS: Intralipid+heparin (IH), saline (SAL), or intralipid+heparin+sodium salicylate (IHS) were separately infused for 7 hours in normal Wistar rats. During the last 2 hours of the infusion, hyperinsulinemic-euglycemic clamping was 3 performed with [6-(3)H] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassay. MDA levels and glutathione peroxidase (GSH-PX) activity in the liver and skeletal muscle were measured with colorimetric kits. RESULTS: Compared with infusion of SAL, IH infusion increased hepatic glucose production (HGP), and decreased glucose utilization (GU) (P<0.05). The elevation of plasma free fatty acids increased the MDA levels and decreased the GSH-PX activity in the liver and muscle (P<0.01). Sodium salicylate treatment decreased HGP, elevated GU (P<0.05), reduced MDA content by 60% (P<0.01), and increased the GSH-PX activity by 35% (P<0.05). CONCLUSIONS: Short-term elevation of fatty acids induces insulin resistance by enhancing oxidative stress levels in the liver and muscle. The administration of the anti-inflammatory drug sodium salicylate reduces the degree of oxidative stress, therefore improving hepatic and peripheral insulin resistance. IKK-beta and NF-kappa B provide potential pathogenic links to oxidative stress.
文摘Non edible oil sources have the potential to lower the cost of biodiesel. However, they usually contain significant high amounts of free fatty acids (FFA) that make them inadequate for direct base catalyzed transesterification reaction (where the FFA content should be lower than 3%). The present work reviews chemical re-esterification as a possible method for the pre-treatment of high FFA feedstock for biodiesel production. The effects of temperature, amount of glycerol, type and amount of catalyst have been discussed. Chemical re-esterification lowers FFA to acceptable levels for transesterification at the same time utilizing the glycerol by product from the same process. Further researches have been proposed as a way forward to improve the process kinetics and optimization so as to make it more economical.
文摘Objective: To investigate the correlation of serum free fatty acid content with glucolipid metabolism, microinflammation and oxidative stress state in patients with type 2 diabetes mellitus. Methods: A total of 189 patients with type 2 diabetes mellitus who were treated in this hospital between August 2015 and February 2018 were chosen as type 2 diabetes mellitus group, and 100 healthy subjects who received physical examination in this hospital during the same period were chosen as the normal control group. The differences in serum levels of FFA, glucolipid metabolism indexes, microinflammation indexes and oxidative stress indexes were compared between the two groups of subjects, and correlation analysis was adopted to judge the inner link of serum FFA content with glucolipid metabolism, microinflammation and oxidative stress state in patients with type 2 diabetes mellitus. Results: Serum FFA content of type 2 diabetes mellitus group was higher than that of control group;serum glucolipid metabolism indexes FPG, 2hPG, TC and LDL-C levels were higher than those of normal control group whereas HDL-C level was lower than that of control group;serum microinflammation indexes IL-1β, IL-6, IL-10, IL-15 and TNF-α contents were higher than those of control group;serum oxidative stress indexes GSH-Px and SOD contents were lower than those of control group whereas ROS and MDA contents were higher than those of control group. Pearson test showed that the serum FFA content of patients with type 2 diabetes mellitus was directly correlated with the contents of glucolipid metabolism, microinflammation and oxidative stress indexes. Conclusion: Serum FFA content significantly increases in patients with type 2 diabetes mellitus, and the specific content was directly correlated with glycolipid metabolism, microinflammation, oxidative stress and other illness indexes.
基金supported by Natural Science Foundation of Shaanxi Province(No.2023-JC-YB-743 and No.2021JQ-905).
文摘Objective Obesity-induced kidney injury contributes to the development of diabetic nephropathy(DN).Here,we identified the functions of ubiquitin-specific peptidase 19(USP19)in HK-2 cells exposed to a combination of high glucose(HG)and free fatty acid(FFA)and determined its association with TGF-beta-activated kinase 1(TAK1).Methods HK-2 cells were exposed to a combination of HG and FFA.USP19 mRNA expression was detected by quantitative RT-PCR(qRT-PCR),and protein analysis was performed by immunoblotting(IB).Cell growth was assessed by Cell Counting Kit-8(CCK-8)viability and 5-ethynyl-2′-deoxyuridine(EdU)proliferation assays.Cell cycle distribution and apoptosis were detected by flow cytometry.The USP19/TAK1 interaction and ubiquitinated TAK1 levels were assayed by coimmunoprecipitation(Co-IP)assays and IB.Results In HG+FFA-challenged HK-2 cells,USP19 was highly expressed.USP19 knockdown attenuated HG+FFA-triggered growth inhibition and apoptosis promotion in HK-2 cells.Moreover,USP19 knockdown alleviated HG+FFA-mediated PTEN-induced putative kinase 1(PINK1)/Parkin pathway inactivation and increased mitochondrial reactive oxygen species(ROS)generation in HK-2 cells.Mechanistically,USP19 stabilized the TAK1 protein through deubiquitination.Importantly,increased TAK1 expression reversed the USP19 knockdown-mediated phenotypic changes and PINK1/Parkin pathway activation in HG+FFA-challenged HK-2 cells.Conclusion The findings revealed that USP19 plays a crucial role in promoting HK-2 cell dysfunction induced by combined stimulation with HG and FFAs by stabilizing TAK1,providing a potential therapeutic strategy for combating DN.
文摘BACKGROUND: Much evidence demonstrates that elevated free fatty acids (FFAs) are associated with insulin resistance. However, it is not clear whether different FFAs can cause different degrees of peripheral insulin resistance. This study aimed to investigate the effects of short-term elevation of FFAs on hepatic and peripheral insulin action, and determine whether FFAs with different degrees of saturation have differential effects on hepatic insulin resistance. METHODS: Intralipid+heparin (IH, polyunsaturated fatty acids), oleate (OLE), lard oil+heparin (LOH), and saline (SAL) were separately infused intravenously for 7 hours in normal Wistar rats. During the last 2 hours of the fat/saline infusion, a hyperinsulinemic-euglycemic clamping was performed with [6-H-3] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassays. Plasma FFAs were measured using a colorimetric method. RESULTS: Compared with infusion of SAL, plasma FFA levels were significantly elevated by infusions of IH, OLE, and LOH (P<0.001). All three fat infusions caused remarkably higher hepatic glucose production (HGP) than SAL (P<0.001). OLE and LOH infusions induced much higher HGP than IH (P<0.01). Glucose utilization (GU) was decreased with all three fat infusions relative to SAL (P<0.001), but GU did not differ among the three types of fat infusions. CONCLUSIONS: Short-term elevation of FFAs can induce hepatic and peripheral insulin resistance. Polyunsaturated fatty acids induced less hepatic insulin resistance than monounsaturated or saturated fatty acids. However, IH, OLE, and LOH infusions induced similar peripheral insulin resistance.
文摘s To investigate the effects of glucose and free fatty acids (FFAs) on the proliferation and cell cycle of human vascular endothelial cells in vitro , and to examine whether the combined presence of elevated FFAs and glucose may cross amplify their individual injurious effects Methods Cultured human vascular endothelial cells (ECV304) were incubated with various concentrations of glucose and/or FFAs (palmitate and/or oleate) for 24-96 h Morphologic alterations were observed using a phase contrast microscope and an electron microscope Inhibition of proliferation was measured by a colorimetric 3 [4, 5 dimethyl thiazol 2 yl] 2, 5 diphenyltetrazolium bromide (MTT) assay Cell viability was determined using trypan blue exclusion Distribution of cells along phases of the cell cycle was analyzed by flow cytometry Results Glucose 15 or 30 mmol/L, palmitate (PA) 0 25 or 0 5 mmol/L, and oleate (OA) 0 5 mmol/L inhibited proliferation and accelerated death of endothelial cells in a dose and time dependent manner After treatment with elevated glucose and/or FFAs, the G 0/G 1 phase cells increased, whereas S phase cells decreased, suggesting that high glucose and/or FFAs mainly arrested endothelial cells at G 0/G 1 phase The inhibitive rates of proliferation and population of dead cells in endothelial cells incubated with glucose plus FFAs (glucose 30 mmol/L+PA 0 25 mmol/L, glucose 30 mmol/L+OA 0 5 mmol/L, glucose 30 mmol/L+PA 0 25 mmol/L+OA 0 5 mmol/L) increased more markedly than those treated with high glucose or FFAs (PA and/or OA) alone Conclusion Both high ambient glucose and FFAs can inhibit proliferation and accelerate death of endothelial cells in vitro These changes were cross amplified in the combined presence of high levels of glucose and FFAs
文摘ResearchGate is a world wide web for scientists and researchers to share papers,ask and answer questions,and find collaborators.As one of the more than 15 million members,the author uploads research output and reads and responds to some of the questions raised,which are related to type 2 diabetes.In that way,he noticed a serious gap of knowledge of this disease among medical professionals over recent decades.The main aim of the current study is to remedy this situation through providing a comprehensive review on recent developments in biochemistry and molecular biology,which can be helpful for the scientific understanding of the molecular nature of type 2 diabetes.To fill up the shortcomings in the curricula of medical education,and to familiarize the medical community with a new concept of the onset of type 2 diabetes,items are discussed like:Insulin resistance,glucose effectiveness,insulin sensitivity,cell membranes,membrane flexibility,unsaturation index(UI;number of carboncarbon double bonds per 100 acyl chains of membrane phospholipids),slowdown principle,effects of temperature acclimation on phospholipid membrane composition,free fatty acids,energy transport,onset of type 2 diabetes,metformin,and exercise.Based on the reviewed data,a new model is presented with proposed steps in the development of type 2 diabetes,a disease arising as a result of a hypothetical hereditary anomaly,which causes hyperthermia in and around the mitochondria.Hyperthermia is counterbalanced by the slow-down principle,which lowers the amount of carbon-carbon double bonds of membrane phospholipid acyl chains.The accompanying reduction in the UI lowers membrane flexibility,promotes a redistribution of the lateral pressure in cell membranes,and thereby reduces the glucose transporter protein pore diameter of the transmembrane glucose transport channel of all Class I GLUT proteins.These events will set up a reduction in transmembrane glucose transport.So,a new blood glucose regulation system,effective in type 2 diabetes and its prediabetic phase,is based on variations in the acyl composition of phospholipids and operates independent of changes in insulin and glucose concentration.UI assessment is currently arising as a promising analytical technology for a membrane flexibility analysis.An increase in mitochondrial heat production plays a pivotal role in the existence of this regulation system.
