Objective:To investigate how Yiqi Yangyin and Huatan Quyu granule (YYHO) improves skeletal muscle insulin resistance in a type 2 diabetic rat model and to discover whether the molecular mechanism is related to the pro...Objective:To investigate how Yiqi Yangyin and Huatan Quyu granule (YYHO) improves skeletal muscle insulin resistance in a type 2 diabetic rat model and to discover whether the molecular mechanism is related to the promotion of the AMPK/SIRT/PGC-1α signalling pathway.Methods:Rats were randomly divided into 4 groups:the normal group,the model group,the YYHQ granule group,and the pioglitazone group.The type 2 diabetic rat model was established by feeding a high-fat diet for 5 weeks along with a single intraperitoneal injection of 30 mg/kg streptozotocin (STZ).After modelling successfully,the appropriate drug was intragastrically administered to diabetic rats for 2 weeks,once per day.The YYHQ granule group was given a dose of 4.8 g/kg body weight per day,the pioglitazone group was given a dose of 1.35 mg/kg body weight per day.The doses for both groups were equivalent to the clinical equivalent dose based on a previous study.Other groups were gavaged with the same amount of saline water.Body weight,food intake,water intake,urine volume and grip strength were recorded weekly.The fasting blood glucose(FBG) was determined weekly using blood glucose test strips.The related glucose and lipid metabolism indexes,e.g.,fasting insulin (Fins),glycated haemoglobin (GHb),HOMA-IR,ISI,triglycerides (TG),total cholesterol (TC),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA),were determined using biochemical method.The mRNA expression levels of adenosine monophosphate-activated protein kinase (AMPK),peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α),carnitine palmitoyl transterase-1 (CPT-1),Sirtuin 1 (SIRT1),and Sirtuin 3 (SIRT3) were assessed using quantitative real-time PCR (qRT-PCR).The protein expression levels of creatine kinase (CK),Ca2+ ATPase,α-Actin,AMPK,PGC-1α and CPT-1 were determined using enzyme-linked immunosorbent assay method (ELISA).Results:Body weight decreased significantly (P <.01),food intake,water intake and urine volume increased significantly (P <.01),and grip strength decreased significantly (P <.01) in the model group compared with the normal group.The levels of FBG,Fins,GHb and HOMA-IR increased significantly (P <.01),and the ISI decreased significantly (P <.01) in the model group.The levels of TG,TC,LDL-C and FFA increased significantly (P <.05 or P <.01),and the level of HDL-C decreased significantly (P <.05) in the model group.These changes were reversed after treatment with YYHQ granule or pioglitazone.Compared with the model group,the YYHQ granule and pioglitazone groups significantly improve body weight,water intake and urine volume (P <.05 or P <.01),however,both treatments had no significant effect on food intake (P >.05).The levels of FBG,Fins,GHb,HOMA-IR and ISI were improved significantly (P <.01) and the levels of TG,TC and LDL-C were improved significantly (P <.05 or P <.01),however,both treatments had no significant effect on the levels of HDL-C and FFA (P >.05).Further results indicated that YYHQ granule significantly decreased the mRNA expression of AMPK,PGC-1α,CPT-1,SIRT1 and SIRT3 in skeletal muscle (P <.01) and the pioglitazone group showed similar effects;moreover,the protein expression levels of CK,Ca2+ATPase,α-Actin,AMPK,PGC-1α and CPT-1 in skeletal muscle significantly decreased (P <.01),however,pioglitazone had no significant effect on CK and α-Actin (P >.05).Conclusion:The possible molecular mechanism of YYHQ granule improving skeletal muscle insulin resistance in a type 2 diabetic rat model may be related to the stimulation of energy metabolism in skeletal muscle via the AMPK/SIRT/PGC-1α signalling pathway.展开更多
Objective:To explore the effect of platelet-rich plasma(RPR)in stimulating the transformation of pro-inflammatory(M1)macrophages into antiinflammatory(M2)under the adenosine-monophosphate-dependent protein kinase(AMPK...Objective:To explore the effect of platelet-rich plasma(RPR)in stimulating the transformation of pro-inflammatory(M1)macrophages into antiinflammatory(M2)under the adenosine-monophosphate-dependent protein kinase(AMPK)signaling pathway.Methods:Rat peritoneal macrophages(RAW264.7)were cultured and randomly divided into 8 groups:blank control group,LPS group,RPR group A,RPR group B,LPS+RPR(12 h)group,LPS+RPR(24 h)group A,LPS+RPR(24 h)group B,LPS+RPR(24 h)group C.RPR was prepared based on blood donors.The expressions of AMPK signaling pathway-related proteins(AMPK,ULK1,m TOR)and macrophage markers(i NOS,Arg-1)in the blank control group,LPS group,LPS+RPR(12 h)group and LPS+RPR(24 h)group were observed and compared.The expressions of macrophage markers in LPS+RPR(24 h)B and C groups were compared,and the expressions of AMPK and TGF-βin RPR A and B groups were compared.Results:The gray values of AMPK and ULK1 in LPS cells decreased significantly,while those in LPS+RPR(12 h)and LPS+RPR(24 h)A cells increased significantly.The gray values of AMPK and ULK1 in LPS+RPR(24 h)A cells were higher than those in LPS+RPR(12 h)cells(P<0.05).The m TOR gray value of LPS cells was significantly higher than that of LPS+RPR(24 h)A cells,and the m TOR gray value of LPS+RPR(24 h)A cells was significantly lower than that of LPS+RPR(12 h)cells(P<0.05).The expression of i NOS in LPS cells was significantly decreased,the expression of i NOS in LPS+RPR(12 h)and LPS+RPR(24 h)cells was significantly increased,and the expression of i NOS in LPS+RPR(24 h)cells was higher than that in LPS+RPR(12 h)cells(P<0.05).The expression of Arg-1 in LPS cells was significantly decreased,the expression of Arg-1 in LPS+RPR(12 h)and LPS+RPR(24 h)A cells was significantly increased,and the expression of Arg-1 in LPS+RPR(24 h)A cells was higher than that in LPS+RPR(12 h)cells(P<0.05).The i NOS expression level of LPS+PRP(24 h)C cells was significantly higher than that of LPS+PRP(24 h)B cells,and the Arg-1 expression level was significantly lower than that of LPS+PRP(24 h)B cells(P<0.05).The gray values of AMPK and TGF-βin PRP B cells were significantly lower than those in PRP A cells(P<0.05).Conclusion:RPR can stimulate macrophage transformation from M1 to M2 by up-regulating AMPK signaling pathway.展开更多
This study aimed to investigate the effect and mechanisms of Ephedra Herb(EH)extract on adriamycin-induced nephrotic syndrome(NS),providing an experimental basis for the clinical treatment of NS.Hematoxylin and eosin ...This study aimed to investigate the effect and mechanisms of Ephedra Herb(EH)extract on adriamycin-induced nephrotic syndrome(NS),providing an experimental basis for the clinical treatment of NS.Hematoxylin and eosin staining,creatinine,urea nitrogen,and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function.The levels of inflammatory factors and oxidative stress were detected by kits.The levels of reactive oxygen species,immune cells,and apoptosis were measured by flow cytometry.A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS.The protein levels of apoptosis-related proteins and CAMKK2,p-CAMKK2,AMPK,p-AMPK,mTOR and p-mTOR in the kidneys were detected by Western blot.The effective material basis of EH extract was screened by MTT assay.The AMPK pathway inhibitor(compound C,CC)was added to investigate the effect of the potent material basis on adriamycin-induced cell injury.EH extract significantly improved renal injury and relieve inflammation,oxidative stress,and apoptosis in rats.Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway.Moreover,methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury.Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR,which were blocked by CC.In sum,EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway.Moreover,methylephedrine may be one of the material bases of EH extract.展开更多
Type 2 diabetes mellitus(T2DM)is a metabolic disease caused by a glycolipid metabolism disorder and isletβ-cell dysfunction.SCP-80-I is a biologically active water-soluble polysaccharide isolated from sweet corncob,a...Type 2 diabetes mellitus(T2DM)is a metabolic disease caused by a glycolipid metabolism disorder and isletβ-cell dysfunction.SCP-80-I is a biologically active water-soluble polysaccharide isolated from sweet corncob,an agricultural byproduct.The hypoglycemic effects of SCP-80-I on T2DM mice and its mechanisms were investigated in this study.SCP-80-I was found to significantly reduce blood glucose and lipid deposition levels in T2DM mice,as well as decrease serum leptin and increase adiponectin secretion.Interestingly,real time-polymerase chain reaction(RT-PCR)and Western blotting results revealed that SCP-80-I could regulate the expression of several glycolipid metabolisms and insulin secretion genes and proteins,including 5'-AMP-activated protein kinase(AMPK),carnitine palmitoyltransferase I(CPTI),and acetyl coenzyme A carboxylase(ACC)in the liver and AMPK,sirtuin1(Sirtl),peroxisome proliferator-activated receptorycoactivator-1(PGC-1α),and uncoupling protein 2(UCP2)in the pancreas.To have a hypoglycemic effect,SCP-80-1 regulated glycolipid metabolism and islet cell function in the liver by regulating the AMPK/AC C/CPT1 signaling pathway and the AMPK/Sirt1/PGC-1αand AMPK/Sirtl/UCP2 signaling pathways.These findings improve our understanding of polysaccharides derived from sweet corncob and the use of SCP-80-I in the production of hypoglycemic foods.展开更多
Dihydromyricetin(DHM),as a bioactive flavanonol compound,is mainly found in“Tengcha”(Ampelopsis grossedentata)cultivated in south of China.This study aimed to investigate the anti-hyperglycemic and antidyslipidemic ...Dihydromyricetin(DHM),as a bioactive flavanonol compound,is mainly found in“Tengcha”(Ampelopsis grossedentata)cultivated in south of China.This study aimed to investigate the anti-hyperglycemic and antidyslipidemic activities of DHM using type 2 diabetes mellitus(T2D)rats,which was induced by feeding with high fat and fructose diet for 42 days and intraperitoneal administration of streptozocin.Forty-eight freshlyweaned rats were randomly assigned into the negative control(Blank),low dose(100 mg/kg),medium dose(200 mg/kg),high dose(400 mg/kg),and positive(40 mg/kg,met)groups.Fasting blood glucose and body weight were measured at weekly interval.Oral glucose tolerance tests were performed on days 42.The results revealed that DHM possessed significant antihyperglycaemic and antihyperinsulinemic effects.Moreover,after the DHM treatment,p-Akt and p-AMPK expression was upregulated,and glycogen synthase kinase-3β(GSK-3β)expression was downregulated,indicating that the potential anti-diabetic mechanism of DHM might be due to the regulation of the AMPK/Akt/GSK-3βsignaling pathway.展开更多
Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and af...Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
基金This research was supported and funded by the National Natural Science Foundation of China(No.81373541).
文摘Objective:To investigate how Yiqi Yangyin and Huatan Quyu granule (YYHO) improves skeletal muscle insulin resistance in a type 2 diabetic rat model and to discover whether the molecular mechanism is related to the promotion of the AMPK/SIRT/PGC-1α signalling pathway.Methods:Rats were randomly divided into 4 groups:the normal group,the model group,the YYHQ granule group,and the pioglitazone group.The type 2 diabetic rat model was established by feeding a high-fat diet for 5 weeks along with a single intraperitoneal injection of 30 mg/kg streptozotocin (STZ).After modelling successfully,the appropriate drug was intragastrically administered to diabetic rats for 2 weeks,once per day.The YYHQ granule group was given a dose of 4.8 g/kg body weight per day,the pioglitazone group was given a dose of 1.35 mg/kg body weight per day.The doses for both groups were equivalent to the clinical equivalent dose based on a previous study.Other groups were gavaged with the same amount of saline water.Body weight,food intake,water intake,urine volume and grip strength were recorded weekly.The fasting blood glucose(FBG) was determined weekly using blood glucose test strips.The related glucose and lipid metabolism indexes,e.g.,fasting insulin (Fins),glycated haemoglobin (GHb),HOMA-IR,ISI,triglycerides (TG),total cholesterol (TC),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA),were determined using biochemical method.The mRNA expression levels of adenosine monophosphate-activated protein kinase (AMPK),peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α),carnitine palmitoyl transterase-1 (CPT-1),Sirtuin 1 (SIRT1),and Sirtuin 3 (SIRT3) were assessed using quantitative real-time PCR (qRT-PCR).The protein expression levels of creatine kinase (CK),Ca2+ ATPase,α-Actin,AMPK,PGC-1α and CPT-1 were determined using enzyme-linked immunosorbent assay method (ELISA).Results:Body weight decreased significantly (P <.01),food intake,water intake and urine volume increased significantly (P <.01),and grip strength decreased significantly (P <.01) in the model group compared with the normal group.The levels of FBG,Fins,GHb and HOMA-IR increased significantly (P <.01),and the ISI decreased significantly (P <.01) in the model group.The levels of TG,TC,LDL-C and FFA increased significantly (P <.05 or P <.01),and the level of HDL-C decreased significantly (P <.05) in the model group.These changes were reversed after treatment with YYHQ granule or pioglitazone.Compared with the model group,the YYHQ granule and pioglitazone groups significantly improve body weight,water intake and urine volume (P <.05 or P <.01),however,both treatments had no significant effect on food intake (P >.05).The levels of FBG,Fins,GHb,HOMA-IR and ISI were improved significantly (P <.01) and the levels of TG,TC and LDL-C were improved significantly (P <.05 or P <.01),however,both treatments had no significant effect on the levels of HDL-C and FFA (P >.05).Further results indicated that YYHQ granule significantly decreased the mRNA expression of AMPK,PGC-1α,CPT-1,SIRT1 and SIRT3 in skeletal muscle (P <.01) and the pioglitazone group showed similar effects;moreover,the protein expression levels of CK,Ca2+ATPase,α-Actin,AMPK,PGC-1α and CPT-1 in skeletal muscle significantly decreased (P <.01),however,pioglitazone had no significant effect on CK and α-Actin (P >.05).Conclusion:The possible molecular mechanism of YYHQ granule improving skeletal muscle insulin resistance in a type 2 diabetic rat model may be related to the stimulation of energy metabolism in skeletal muscle via the AMPK/SIRT/PGC-1α signalling pathway.
文摘Objective:To explore the effect of platelet-rich plasma(RPR)in stimulating the transformation of pro-inflammatory(M1)macrophages into antiinflammatory(M2)under the adenosine-monophosphate-dependent protein kinase(AMPK)signaling pathway.Methods:Rat peritoneal macrophages(RAW264.7)were cultured and randomly divided into 8 groups:blank control group,LPS group,RPR group A,RPR group B,LPS+RPR(12 h)group,LPS+RPR(24 h)group A,LPS+RPR(24 h)group B,LPS+RPR(24 h)group C.RPR was prepared based on blood donors.The expressions of AMPK signaling pathway-related proteins(AMPK,ULK1,m TOR)and macrophage markers(i NOS,Arg-1)in the blank control group,LPS group,LPS+RPR(12 h)group and LPS+RPR(24 h)group were observed and compared.The expressions of macrophage markers in LPS+RPR(24 h)B and C groups were compared,and the expressions of AMPK and TGF-βin RPR A and B groups were compared.Results:The gray values of AMPK and ULK1 in LPS cells decreased significantly,while those in LPS+RPR(12 h)and LPS+RPR(24 h)A cells increased significantly.The gray values of AMPK and ULK1 in LPS+RPR(24 h)A cells were higher than those in LPS+RPR(12 h)cells(P<0.05).The m TOR gray value of LPS cells was significantly higher than that of LPS+RPR(24 h)A cells,and the m TOR gray value of LPS+RPR(24 h)A cells was significantly lower than that of LPS+RPR(12 h)cells(P<0.05).The expression of i NOS in LPS cells was significantly decreased,the expression of i NOS in LPS+RPR(12 h)and LPS+RPR(24 h)cells was significantly increased,and the expression of i NOS in LPS+RPR(24 h)cells was higher than that in LPS+RPR(12 h)cells(P<0.05).The expression of Arg-1 in LPS cells was significantly decreased,the expression of Arg-1 in LPS+RPR(12 h)and LPS+RPR(24 h)A cells was significantly increased,and the expression of Arg-1 in LPS+RPR(24 h)A cells was higher than that in LPS+RPR(12 h)cells(P<0.05).The i NOS expression level of LPS+PRP(24 h)C cells was significantly higher than that of LPS+PRP(24 h)B cells,and the Arg-1 expression level was significantly lower than that of LPS+PRP(24 h)B cells(P<0.05).The gray values of AMPK and TGF-βin PRP B cells were significantly lower than those in PRP A cells(P<0.05).Conclusion:RPR can stimulate macrophage transformation from M1 to M2 by up-regulating AMPK signaling pathway.
基金the National Key Research and Development Project(Nos.2019YFC1708802 and 2017YFC1702800)Henan province high-level personnel special support“ZhongYuan One Thousand People Pla”,Zhongyuan Leading Talent(No.ZYQR201810080)the Major Science and Technology Projects in Henan Province:Study on the key technology for quality control and the key characteristics of Rehmannia glutinosa,Dioscorea opposita Thunb.and Achyranthes bidentata Blume from Henan Province(No.171100310500).
文摘This study aimed to investigate the effect and mechanisms of Ephedra Herb(EH)extract on adriamycin-induced nephrotic syndrome(NS),providing an experimental basis for the clinical treatment of NS.Hematoxylin and eosin staining,creatinine,urea nitrogen,and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function.The levels of inflammatory factors and oxidative stress were detected by kits.The levels of reactive oxygen species,immune cells,and apoptosis were measured by flow cytometry.A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS.The protein levels of apoptosis-related proteins and CAMKK2,p-CAMKK2,AMPK,p-AMPK,mTOR and p-mTOR in the kidneys were detected by Western blot.The effective material basis of EH extract was screened by MTT assay.The AMPK pathway inhibitor(compound C,CC)was added to investigate the effect of the potent material basis on adriamycin-induced cell injury.EH extract significantly improved renal injury and relieve inflammation,oxidative stress,and apoptosis in rats.Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway.Moreover,methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury.Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR,which were blocked by CC.In sum,EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway.Moreover,methylephedrine may be one of the material bases of EH extract.
基金financially supported by the Doctoral Scientific Research Start-up Foundation of the Harbin University of Commerce (2019DS098)the Young Innovation Talents Project from the Harbin University of Commerce (2019CX31)the Graduate Innovation Fund from the Harbin University of Commerce (YJSCX2019–615HSD)。
文摘Type 2 diabetes mellitus(T2DM)is a metabolic disease caused by a glycolipid metabolism disorder and isletβ-cell dysfunction.SCP-80-I is a biologically active water-soluble polysaccharide isolated from sweet corncob,an agricultural byproduct.The hypoglycemic effects of SCP-80-I on T2DM mice and its mechanisms were investigated in this study.SCP-80-I was found to significantly reduce blood glucose and lipid deposition levels in T2DM mice,as well as decrease serum leptin and increase adiponectin secretion.Interestingly,real time-polymerase chain reaction(RT-PCR)and Western blotting results revealed that SCP-80-I could regulate the expression of several glycolipid metabolisms and insulin secretion genes and proteins,including 5'-AMP-activated protein kinase(AMPK),carnitine palmitoyltransferase I(CPTI),and acetyl coenzyme A carboxylase(ACC)in the liver and AMPK,sirtuin1(Sirtl),peroxisome proliferator-activated receptorycoactivator-1(PGC-1α),and uncoupling protein 2(UCP2)in the pancreas.To have a hypoglycemic effect,SCP-80-1 regulated glycolipid metabolism and islet cell function in the liver by regulating the AMPK/AC C/CPT1 signaling pathway and the AMPK/Sirt1/PGC-1αand AMPK/Sirtl/UCP2 signaling pathways.These findings improve our understanding of polysaccharides derived from sweet corncob and the use of SCP-80-I in the production of hypoglycemic foods.
基金the National Natural Science Foundation of China(NSFC,Grant No.31801459,31701520)Science and Technology General Projects of Fujian Province(2019J01393)Educational research project for young and middleaged teachers in Fujian Province(JT180116).
文摘Dihydromyricetin(DHM),as a bioactive flavanonol compound,is mainly found in“Tengcha”(Ampelopsis grossedentata)cultivated in south of China.This study aimed to investigate the anti-hyperglycemic and antidyslipidemic activities of DHM using type 2 diabetes mellitus(T2D)rats,which was induced by feeding with high fat and fructose diet for 42 days and intraperitoneal administration of streptozocin.Forty-eight freshlyweaned rats were randomly assigned into the negative control(Blank),low dose(100 mg/kg),medium dose(200 mg/kg),high dose(400 mg/kg),and positive(40 mg/kg,met)groups.Fasting blood glucose and body weight were measured at weekly interval.Oral glucose tolerance tests were performed on days 42.The results revealed that DHM possessed significant antihyperglycaemic and antihyperinsulinemic effects.Moreover,after the DHM treatment,p-Akt and p-AMPK expression was upregulated,and glycogen synthase kinase-3β(GSK-3β)expression was downregulated,indicating that the potential anti-diabetic mechanism of DHM might be due to the regulation of the AMPK/Akt/GSK-3βsignaling pathway.
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
