Glucagon-like peptide- 1 （GLP- 1） has been endorsed as a promising and attractive agent in the treatment of type 2 diabetes mellitus （T2DM）. Both Alzheimer＇s disease （AD） and T2DM share some common pathophysiol...Glucagon-like peptide- 1 （GLP- 1） has been endorsed as a promising and attractive agent in the treatment of type 2 diabetes mellitus （T2DM）. Both Alzheimer＇s disease （AD） and T2DM share some common pathophysiologic hallmarks, such as amyloid β （Aβ）, phosphoralation of tau protein, and glycogen synthase kinase-3. GLP-1 possesses neurotropic properties and can reduce amyloid protein levels in the brain. Based on extensive studies during the past decades, the understanding on AD leads us to believe that the primary targets in AD are the Aβ and tau protein. Combine these findings, GLP- 1 is probably a promising agent in the therapy of AD. This review was focused on the biochemistry and physiology of GLP- 1, communities between T2DM and AD, new progresses of GLP - 1 in treating T2MD and improving some pathologic hanmarks of AD.展开更多
Baekgound Recent studies have suggested a potential role for liraglutide in the prevention and stabilization ofatherosclerotic vascular disease. However, the molecular mechanisms underlying the effect of liraglutide o...Baekgound Recent studies have suggested a potential role for liraglutide in the prevention and stabilization ofatherosclerotic vascular disease. However, the molecular mechanisms underlying the effect of liraglutide on atherosclerosis have not been well elucidated. The pur- pose of this study was to examine whether liraglutide protects against oxidative stress and fatty degeneration via modulation of AMP-activated protein kinase （AMPK）/sterol regulatory element binding transcription factor 1 （SREBP1） signaling pathway in foam ceils. Methods Mouse macrophages Raw264.7 cells were exposed to oxidized low density lipoprotein （oxLDL） to induce the formation of foam cells. The cells were incubated with oxLDL （50 μg/mL）, liraglutide （0.1, 0.5, 1 and 2 nmol/L） or exendin-3 （9-39） （1, 10 and 100 nmol/L） alone, or in combination. Oil Red O staining was used to detect intracellular lipid droplets. The levels of TG and cholesterol were measured using the commercial kits. Oxidative stress was determined by measuring intracellular reactive oxygen species （ROS）, malondialdehyde （MDA） and superoxide dismutase 1 （SOD）. Western blot analysis was used to examine the expression of AMPKal, SREBP1, phosphory- lated AMPKal, phosphorylated SREBP1, glucagon-like peptide-1 （GLP-1） and GLP-1 receptor （GLP-1R）. Results Oil Red O staining showed that the cytoplasmic lipid droplet accumulation was visibly decreased in foam cells by treatment with liraglutide. The TG and cholesterol content in the liraglutide-treated foam cells was significantly decreased. In addition, foam ceils manifested an impaired oxidative stress following liraglutide treatment, as evidenced by increased SOD, and decreased ROS and MDA. However, these effects of liraglutide on foam cells were attenuated by the use of GLP-IR antagonist exendin-3 （9-39）. Furthermore, we found that the expression level of AMPKa 1 and phosphorylated AMPKct 1 was significantly increased while the expression level of SREBP 1 and phosphorylated SREBP 1 was significantly decreased in foam cells following treatment with liraglutide. Conclusions This study for the first time demonstrated that the effect of liraglutide on reducing oxidative stress and fatty degeneration in oxLDL-induced Raw264.7 cells is accompanied by the alteration of AMPK/SREBP1 pathway. This study provided a potential molecular mechanism for the effect of liraglutide on reducing oxidative stress and fatty degeneration.展开更多
AIM:To investigate whether uncoupling protein 2(UCP2) affects oleic acid-induced secretion of glucagonlike peptide-1(GLP-1) in L-cells.METHODS:mRNA and protein expression of UCP2 were analyzed in human NCI-H716 cells,...AIM:To investigate whether uncoupling protein 2(UCP2) affects oleic acid-induced secretion of glucagonlike peptide-1(GLP-1) in L-cells.METHODS:mRNA and protein expression of UCP2 were analyzed in human NCI-H716 cells,which serve as a model for enteroendocrine L-cells,by quantitative reverse transcription-polymerase chain reaction and Western blotting before and after treatment with oleic acid.Localization of UCP2 and GLP-1 in NCI-H716 cells was assessed by immunofluorescence labeling.NCI-H716 cells were transiently transfected with a small interfering RNA(siRNA) that targets UCP2(siUCP2) or with a nonspecific siRNA using Lipofectamine 2000.The concentrations of bioactive GLP-1 in the medium were measured by enzyme linked immunosorbent assay.RESULTS:Both GLP-1 and UCP2 granules were expressed mainly in the cytoplasm of NCI-H716 cells.NCI-H716 cells that secreted GLP-1 also expressed UCP2.Time-course experiments revealed that release of GLP-1 from NCI-H716 cells into the medium reached a maximum at 120 min and remained stable until at least 180 min after treatment with oleic acid(the level of GLP-1 increased about 2.3-fold as compared with the level of GLP-1 in the control cells,P < 0.05).In an experiment to determine dose dependence,stimulation of NCI-H716 cells with ≤ 8 mmol oleic acid led to a concentration-dependent release of GLP-1 into the medium;10 mmol oleic acid diminished the release of GLP-1.Furthermore,GLP-1 secretion induced by oleic acid from NCI-H716 cells that were transfected with siUCP2 decreased to 41.8%,as compared with NCI-H716 cells that were transfected with a non-specific siRNA(P < 0.01).CONCLUSION:UCP2 affected GLP-1 secretion induced by oleic acid.UCP2 plays an important role in L-cell secretion that is induced by free fatty acids.展开更多
The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistan...The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives.展开更多
Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are novel hypoglycemic agents that have garnered widespread acceptance in the treatment of type 2 diabetes,largely attributed to their safety profile,potent hypoglyce...Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are novel hypoglycemic agents that have garnered widespread acceptance in the treatment of type 2 diabetes,largely attributed to their safety profile,potent hypoglycemic effects,and metabolic advantages.Their primary mechanisms of action encompass promoting insulin release,inhibiting glucagon secretion,bolstering pancreatic islet cell function,curbing appetite,and slowing gastric emptying.This article delves into the clinical evidence underscoring the efficacy of various GLP-1RAs.Notably,these agents have demonstrated marked improvements in glycemic control,significant weight reduction,and substantial cardiovascular and renal protection.Nonetheless,certain adverse effects of GLP-1RAs,such as pancreatitis and intestinal obstruction,have been reported,warranting vigilant monitoring by healthcare professionals.In sum,GLP-1RAs hold significant promise in the management of type 2 diabetes,offering notable cardiovascular and renal advantages.展开更多
Objective:To observe the effects of acupoint thread-embedding therapy on serum apelin and glucagon-like peptide-1(GLP-1)in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen.Methods...Objective:To observe the effects of acupoint thread-embedding therapy on serum apelin and glucagon-like peptide-1(GLP-1)in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen.Methods:Sixty-six patients were randomly divided into a control group and an observation group according to the random number table method,with 33 cases in each group.Patients in the control group were treated with exenatide and metformin,while patients in the observation group were treated with additional acupoint thread-embedding.After 12-week treatment,the obesity-related indicators,including body mass index(BMI),waist circumference and body fat rate,the glycometabolism indicators,including fasting blood glucose,2 h postprandial blood glucose and glycosylated hemoglobin,and the lipid metabolism indicators,including total cholesterol(TC),triglyceride(TG)and low-density lipoprotein cholesterol(LDL-C),as well as serum apelin and GLP-1 levels were observed in patients of the two groups.Results:After treatment,the BMI,waist circumference and body fat rate of patients in the two groups were all reduced(all P<0.05),and were lower in the observation group than in the control group(all P<0.05);the fasting blood glucose,2 h postprandial blood glucose and glycosylated hemoglobin levels of patients in both groups were all decreased(all P<0.05),and were significantly lower in the observation group than in the control group(all P<0.05);the TC level was decreased(P<0.05),while the TG and LDL-C levels did not change significantly in the control group(both P>0.05);the TC,TG and LDL-C levels were all significantly reduced in the observation group(all P<0.05),lower than those in the control group(all P<0.05);the serum apelin level was decreased(P<0.05)and the serum GLP-1 level was increased(P<0.05)in the observation group,statistically different from those in the control group(both P<0.05).Conclusion:Combined with the conventional medication,acupoint thread-embedding therapy can significantly improve the obesity-related indicators,glycometabolism and lipid metabolism in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen.This may be achieved by regulating the serum apelin and GLP-1 levels.展开更多
Objective： To observe the clinical efficacy of electroacupuncture for functional dyspepsia（FD）, and explore the corresponding mechanism.Methods： Sixty-four FD patients were randomly divided into electroacupuncture...Objective： To observe the clinical efficacy of electroacupuncture for functional dyspepsia（FD）, and explore the corresponding mechanism.Methods： Sixty-four FD patients were randomly divided into electroacupuncture group and western medicine group, with 32 cases in each group. In electroacupuncture group, electroacupuncture at Zusanli（足三里ST 36）,Sanyinjiao（三阴交SP 6）,Gongsun（公孙SP 4） and Neiguan（内关PC 6） was performed for once a day, and the needles were retained for 30 min. In western medicine group, oral administration of mosapride citrate dispersible tablets in a dosage of 5 mg/time was carried out for 3 times a day. Treatment was conducted for 30 consecutive days in both groups. The scores of Leeds dyspepsia questionnaire（LDQ） and functional digestive disorder quality of life（FDDQL） of patients in both groups were recorded before and after treatment. Serum Ghrelin, CGRP and GLP-1 levels of patients were tested before and after treatment respectively, and the clinical efficacy of patients in both groups was evaluated after treatment.Results： In western medicine group, LDQ score after treatment was lower than that before treatment（P 0.05）, FDDQL score after treatment was higher than that before treatment, while the differences were not statistically significant（P0.05）. LDQ score in electroacupuncture group after treatment was lower than that before treatment（P0.05）, and also lower than that in western medicine group at the same time point（P 0.05）. FDDQL score in electroacupuncture group after treatment was higher than that before treatment（P0.05）, and also higher than that in western medicine group at the same time point（P0.05）. In western medicine group, Ghrelin level after treatment was higher than that before treatment（P 0.05）, CGRP level reduced, and the differences were not statistically significant（P 0.05）. GLP-1 level after treatment was also higher than that before treatment（P0.05）. In electroacupuncture group,Ghrelin level after treatment was higher than that before treatment, CGRP level reduced, and GLP-1 level after treatment was also higher than that before treatment（both P 0.05）. According to the comparison of values of each index between electroacupuncture group and western medicine group after treatment,the differences were all statistically significant（all P 0.05）. The total effective rate in electroacupuncture group was 90.63%（29/32） which was higher than that in western medicine group 68.75%（22/32）, and the differences were statistically significant（P0.05）.Conclusion： Electroacupuncture at ST 36, SP 6, SP 4 and PC 6 can effectively improve the clinical symptoms of FD patients, and the mechanism might be related with the increase of serum Ghrelin and GLP-1 levels and the decrease of serum CGRP level.展开更多
文摘Glucagon-like peptide- 1 （GLP- 1） has been endorsed as a promising and attractive agent in the treatment of type 2 diabetes mellitus （T2DM）. Both Alzheimer＇s disease （AD） and T2DM share some common pathophysiologic hallmarks, such as amyloid β （Aβ）, phosphoralation of tau protein, and glycogen synthase kinase-3. GLP-1 possesses neurotropic properties and can reduce amyloid protein levels in the brain. Based on extensive studies during the past decades, the understanding on AD leads us to believe that the primary targets in AD are the Aβ and tau protein. Combine these findings, GLP- 1 is probably a promising agent in the therapy of AD. This review was focused on the biochemistry and physiology of GLP- 1, communities between T2DM and AD, new progresses of GLP - 1 in treating T2MD and improving some pathologic hanmarks of AD.
文摘Baekgound Recent studies have suggested a potential role for liraglutide in the prevention and stabilization ofatherosclerotic vascular disease. However, the molecular mechanisms underlying the effect of liraglutide on atherosclerosis have not been well elucidated. The pur- pose of this study was to examine whether liraglutide protects against oxidative stress and fatty degeneration via modulation of AMP-activated protein kinase （AMPK）/sterol regulatory element binding transcription factor 1 （SREBP1） signaling pathway in foam ceils. Methods Mouse macrophages Raw264.7 cells were exposed to oxidized low density lipoprotein （oxLDL） to induce the formation of foam cells. The cells were incubated with oxLDL （50 μg/mL）, liraglutide （0.1, 0.5, 1 and 2 nmol/L） or exendin-3 （9-39） （1, 10 and 100 nmol/L） alone, or in combination. Oil Red O staining was used to detect intracellular lipid droplets. The levels of TG and cholesterol were measured using the commercial kits. Oxidative stress was determined by measuring intracellular reactive oxygen species （ROS）, malondialdehyde （MDA） and superoxide dismutase 1 （SOD）. Western blot analysis was used to examine the expression of AMPKal, SREBP1, phosphory- lated AMPKal, phosphorylated SREBP1, glucagon-like peptide-1 （GLP-1） and GLP-1 receptor （GLP-1R）. Results Oil Red O staining showed that the cytoplasmic lipid droplet accumulation was visibly decreased in foam cells by treatment with liraglutide. The TG and cholesterol content in the liraglutide-treated foam cells was significantly decreased. In addition, foam ceils manifested an impaired oxidative stress following liraglutide treatment, as evidenced by increased SOD, and decreased ROS and MDA. However, these effects of liraglutide on foam cells were attenuated by the use of GLP-IR antagonist exendin-3 （9-39）. Furthermore, we found that the expression level of AMPKa 1 and phosphorylated AMPKct 1 was significantly increased while the expression level of SREBP 1 and phosphorylated SREBP 1 was significantly decreased in foam cells following treatment with liraglutide. Conclusions This study for the first time demonstrated that the effect of liraglutide on reducing oxidative stress and fatty degeneration in oxLDL-induced Raw264.7 cells is accompanied by the alteration of AMPK/SREBP1 pathway. This study provided a potential molecular mechanism for the effect of liraglutide on reducing oxidative stress and fatty degeneration.
基金Supported by Grant from the National Natural Science Foundation of China,No. 30771039
文摘AIM:To investigate whether uncoupling protein 2(UCP2) affects oleic acid-induced secretion of glucagonlike peptide-1(GLP-1) in L-cells.METHODS:mRNA and protein expression of UCP2 were analyzed in human NCI-H716 cells,which serve as a model for enteroendocrine L-cells,by quantitative reverse transcription-polymerase chain reaction and Western blotting before and after treatment with oleic acid.Localization of UCP2 and GLP-1 in NCI-H716 cells was assessed by immunofluorescence labeling.NCI-H716 cells were transiently transfected with a small interfering RNA(siRNA) that targets UCP2(siUCP2) or with a nonspecific siRNA using Lipofectamine 2000.The concentrations of bioactive GLP-1 in the medium were measured by enzyme linked immunosorbent assay.RESULTS:Both GLP-1 and UCP2 granules were expressed mainly in the cytoplasm of NCI-H716 cells.NCI-H716 cells that secreted GLP-1 also expressed UCP2.Time-course experiments revealed that release of GLP-1 from NCI-H716 cells into the medium reached a maximum at 120 min and remained stable until at least 180 min after treatment with oleic acid(the level of GLP-1 increased about 2.3-fold as compared with the level of GLP-1 in the control cells,P < 0.05).In an experiment to determine dose dependence,stimulation of NCI-H716 cells with ≤ 8 mmol oleic acid led to a concentration-dependent release of GLP-1 into the medium;10 mmol oleic acid diminished the release of GLP-1.Furthermore,GLP-1 secretion induced by oleic acid from NCI-H716 cells that were transfected with siUCP2 decreased to 41.8%,as compared with NCI-H716 cells that were transfected with a non-specific siRNA(P < 0.01).CONCLUSION:UCP2 affected GLP-1 secretion induced by oleic acid.UCP2 plays an important role in L-cell secretion that is induced by free fatty acids.
文摘The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives.
基金R&D Program of the Beijing Municipal Education Commission(Grant No.KM202110025001).
文摘Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are novel hypoglycemic agents that have garnered widespread acceptance in the treatment of type 2 diabetes,largely attributed to their safety profile,potent hypoglycemic effects,and metabolic advantages.Their primary mechanisms of action encompass promoting insulin release,inhibiting glucagon secretion,bolstering pancreatic islet cell function,curbing appetite,and slowing gastric emptying.This article delves into the clinical evidence underscoring the efficacy of various GLP-1RAs.Notably,these agents have demonstrated marked improvements in glycemic control,significant weight reduction,and substantial cardiovascular and renal protection.Nonetheless,certain adverse effects of GLP-1RAs,such as pancreatitis and intestinal obstruction,have been reported,warranting vigilant monitoring by healthcare professionals.In sum,GLP-1RAs hold significant promise in the management of type 2 diabetes,offering notable cardiovascular and renal advantages.
文摘Objective:To observe the effects of acupoint thread-embedding therapy on serum apelin and glucagon-like peptide-1(GLP-1)in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen.Methods:Sixty-six patients were randomly divided into a control group and an observation group according to the random number table method,with 33 cases in each group.Patients in the control group were treated with exenatide and metformin,while patients in the observation group were treated with additional acupoint thread-embedding.After 12-week treatment,the obesity-related indicators,including body mass index(BMI),waist circumference and body fat rate,the glycometabolism indicators,including fasting blood glucose,2 h postprandial blood glucose and glycosylated hemoglobin,and the lipid metabolism indicators,including total cholesterol(TC),triglyceride(TG)and low-density lipoprotein cholesterol(LDL-C),as well as serum apelin and GLP-1 levels were observed in patients of the two groups.Results:After treatment,the BMI,waist circumference and body fat rate of patients in the two groups were all reduced(all P<0.05),and were lower in the observation group than in the control group(all P<0.05);the fasting blood glucose,2 h postprandial blood glucose and glycosylated hemoglobin levels of patients in both groups were all decreased(all P<0.05),and were significantly lower in the observation group than in the control group(all P<0.05);the TC level was decreased(P<0.05),while the TG and LDL-C levels did not change significantly in the control group(both P>0.05);the TC,TG and LDL-C levels were all significantly reduced in the observation group(all P<0.05),lower than those in the control group(all P<0.05);the serum apelin level was decreased(P<0.05)and the serum GLP-1 level was increased(P<0.05)in the observation group,statistically different from those in the control group(both P<0.05).Conclusion:Combined with the conventional medication,acupoint thread-embedding therapy can significantly improve the obesity-related indicators,glycometabolism and lipid metabolism in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen.This may be achieved by regulating the serum apelin and GLP-1 levels.
文摘Objective： To observe the clinical efficacy of electroacupuncture for functional dyspepsia（FD）, and explore the corresponding mechanism.Methods： Sixty-four FD patients were randomly divided into electroacupuncture group and western medicine group, with 32 cases in each group. In electroacupuncture group, electroacupuncture at Zusanli（足三里ST 36）,Sanyinjiao（三阴交SP 6）,Gongsun（公孙SP 4） and Neiguan（内关PC 6） was performed for once a day, and the needles were retained for 30 min. In western medicine group, oral administration of mosapride citrate dispersible tablets in a dosage of 5 mg/time was carried out for 3 times a day. Treatment was conducted for 30 consecutive days in both groups. The scores of Leeds dyspepsia questionnaire（LDQ） and functional digestive disorder quality of life（FDDQL） of patients in both groups were recorded before and after treatment. Serum Ghrelin, CGRP and GLP-1 levels of patients were tested before and after treatment respectively, and the clinical efficacy of patients in both groups was evaluated after treatment.Results： In western medicine group, LDQ score after treatment was lower than that before treatment（P 0.05）, FDDQL score after treatment was higher than that before treatment, while the differences were not statistically significant（P0.05）. LDQ score in electroacupuncture group after treatment was lower than that before treatment（P0.05）, and also lower than that in western medicine group at the same time point（P 0.05）. FDDQL score in electroacupuncture group after treatment was higher than that before treatment（P0.05）, and also higher than that in western medicine group at the same time point（P0.05）. In western medicine group, Ghrelin level after treatment was higher than that before treatment（P 0.05）, CGRP level reduced, and the differences were not statistically significant（P 0.05）. GLP-1 level after treatment was also higher than that before treatment（P0.05）. In electroacupuncture group,Ghrelin level after treatment was higher than that before treatment, CGRP level reduced, and GLP-1 level after treatment was also higher than that before treatment（both P 0.05）. According to the comparison of values of each index between electroacupuncture group and western medicine group after treatment,the differences were all statistically significant（all P 0.05）. The total effective rate in electroacupuncture group was 90.63%（29/32） which was higher than that in western medicine group 68.75%（22/32）, and the differences were statistically significant（P0.05）.Conclusion： Electroacupuncture at ST 36, SP 6, SP 4 and PC 6 can effectively improve the clinical symptoms of FD patients, and the mechanism might be related with the increase of serum Ghrelin and GLP-1 levels and the decrease of serum CGRP level.
