Gluconeogenesis is an endogenous process of glucose production from noncarbohydrate carbon substrates.Both the liver and kidneys express the key enzymes necessary for endogenous glucose production and its export into ...Gluconeogenesis is an endogenous process of glucose production from noncarbohydrate carbon substrates.Both the liver and kidneys express the key enzymes necessary for endogenous glucose production and its export into circulation.We would be remiss to add that more recently gluconeogenesis has been described in the small intestine,especially under high-protein,lowcarbohydrate diets.The contribution of the liver glucose release,the net glucose flux,towards systemic glucose is already well known.The liver is,in most instances,the primary bulk contributor due to the sheer size of the organ(on average,over 1 kg).The contribution of the kidney(at just over 100 g each)to endogenous glucose production is often under-appreciated,especially on a weight basis.Glucose is released from the liver through the process of glycogenolysis and gluconeogenesis.Renal glucose release is almost exclusively due to gluconeogenesis,which occurs in only a fraction of the cells in that organ(proximal tubule cells).Thus,the efficiency of glucose production from other carbon sources may be superior in the kidney relative to the liver or at least on the level.In both these tissues,gluconeogenesis regulation is under tight hormonal control and depends on the availability of substrates.Liver and renal gluconeogenesis are differentially regulated under various pathological conditions.The impact of one source vs the other changes,based on post-prandial state,acid-base balance,hormonal status,and other less understood factors.Which organ has the oar(is more influential)in driving systemic glucose homeostasis is still inconclusive and likely changes with the daily rhythms of life.We reviewed the literature on the differences in gluconeogenesis regulation between the kidneys and the liver to gain an insight into who drives the systemic glucose levels under various physiological and pathological conditions.展开更多
Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma.The progress of liver fibrosis and cirrhosis is accompanied by deterioratin...Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma.The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function.This review summarizes the regulatory and functional changes in phase Ⅰ and phaseⅡmetabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients.Interestingly,phase Ⅰ enzymes are generally down regulated transcriptionally,while phaseⅡenzymes are mostly preserved transcriptionally but are reduced in their function.Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis.Lipid and glucose metabolism are characterized by insulin resistance and catabolism,leading to the disturbance of energy expenditure and wasting.Possible non-invasive tests,especially breath tests,for components of liver metabolism are discussed.The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients.Additionally,studies in humans are rare,and species differences preclude the transferability of data from rodents to humans.In clinical practice,some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis,but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests.展开更多
目的探讨水飞蓟宾治疗初诊2型糖尿病(T2DM)伴非酒精性脂肪肝(NAFLD)对患者肝纤维化进程、糖脂代谢紊乱的调节效果。方法选取2016年1月—2019年1月湖南省脑科医院收治的93例初诊T2DM伴NAFLD患者作为研究对象,采用随机数字表分为观察组47...目的探讨水飞蓟宾治疗初诊2型糖尿病(T2DM)伴非酒精性脂肪肝(NAFLD)对患者肝纤维化进程、糖脂代谢紊乱的调节效果。方法选取2016年1月—2019年1月湖南省脑科医院收治的93例初诊T2DM伴NAFLD患者作为研究对象,采用随机数字表分为观察组47例和对照组46例。两组患者均采取运动、饮食干预+二甲双胍治疗,观察组同时服用水飞蓟宾治疗;对比两组治疗前后的空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)、三酰甘油(TG)、脂联素、瘦素、白细胞介素-6(IL-6)、超氧化物歧化酶(SOD)、Ⅲ型前胶原肽(Ⅲ-PC)、层黏蛋白(LN)、透明质酸(HA)、肝脏彩超评分及不良反应。结果治疗前,两组FPG、2 h PG、HbA1c、HOMA-IR、TC、TG、脂联素、瘦素、IL-6、SOD、彩超评分、Ⅲ-PC、LN、HA测定值比较,差异无统计学意义(P>0.05);治疗后,两组FPG、2 h PG、HbA1c、HOMA-IR、TC、TG、瘦素、IL-6、彩超评分、Ⅲ-PC、LN、HA较治疗前均降低,脂联素、SOD水平较治疗前均升高(均P<0.05),且观察组的TC、TG、瘦素、IL-6、彩超评分、Ⅲ-PC、LN、HA低于对照组,脂联素、SOD水平高于对照组(均P<0.05);两组不良反应发生率差异无统计学意义(P>0.05)。结论T2DM伴NAFLD患者采用水飞蓟宾联合运动、饮食干预+二甲双胍治疗在良好的控制血糖基础上,还能抑制肝纤维化进程,调节糖脂代谢紊乱,临床效果值得肯定。展开更多
Long non-coding RNAs(lncRNAs)are comprised of RNA transcripts exceeding 200 nucleotides in length but lacking identifiable open reading frames(with rare exceptions).Herein,we highlight emerging evidence demonstrating ...Long non-coding RNAs(lncRNAs)are comprised of RNA transcripts exceeding 200 nucleotides in length but lacking identifiable open reading frames(with rare exceptions).Herein,we highlight emerging evidence demonstrating that lncRNAs are critical regulators of liver metabolic function and diseases.We summarize current knowledges about dysregulated lncRNAs and outline the underlying molecular mechanisms by which lncRNAs control hepatic lipid ad glucose metabolism,as well as cholestatic liver disease.Liver-specific triglyceride regulator(lncLSTR),Lnc18q22.2,steroid RNA activator(SRA),highly upregulated in liver cancer(HULC),metastasis associated in lung adenocarcinoma transcript 1(MALAT1),liver glucokinase repressor(lncLGR),maternally expressed gene 3(MEG3),and H19,lncHR1,lnc-HC,apolipoprotein A1 antisense transcript(APOA1-AS),DYNLRB2-2,and LXR-induced sequence(LeXis)are included in the discussion.展开更多
基金Supported by the Indian Council of Medical Research grant to S.T,No.Coord/7(1)/CARE-KD/2018/NCD-II.
文摘Gluconeogenesis is an endogenous process of glucose production from noncarbohydrate carbon substrates.Both the liver and kidneys express the key enzymes necessary for endogenous glucose production and its export into circulation.We would be remiss to add that more recently gluconeogenesis has been described in the small intestine,especially under high-protein,lowcarbohydrate diets.The contribution of the liver glucose release,the net glucose flux,towards systemic glucose is already well known.The liver is,in most instances,the primary bulk contributor due to the sheer size of the organ(on average,over 1 kg).The contribution of the kidney(at just over 100 g each)to endogenous glucose production is often under-appreciated,especially on a weight basis.Glucose is released from the liver through the process of glycogenolysis and gluconeogenesis.Renal glucose release is almost exclusively due to gluconeogenesis,which occurs in only a fraction of the cells in that organ(proximal tubule cells).Thus,the efficiency of glucose production from other carbon sources may be superior in the kidney relative to the liver or at least on the level.In both these tissues,gluconeogenesis regulation is under tight hormonal control and depends on the availability of substrates.Liver and renal gluconeogenesis are differentially regulated under various pathological conditions.The impact of one source vs the other changes,based on post-prandial state,acid-base balance,hormonal status,and other less understood factors.Which organ has the oar(is more influential)in driving systemic glucose homeostasis is still inconclusive and likely changes with the daily rhythms of life.We reviewed the literature on the differences in gluconeogenesis regulation between the kidneys and the liver to gain an insight into who drives the systemic glucose levels under various physiological and pathological conditions.
文摘Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma.The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function.This review summarizes the regulatory and functional changes in phase Ⅰ and phaseⅡmetabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients.Interestingly,phase Ⅰ enzymes are generally down regulated transcriptionally,while phaseⅡenzymes are mostly preserved transcriptionally but are reduced in their function.Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis.Lipid and glucose metabolism are characterized by insulin resistance and catabolism,leading to the disturbance of energy expenditure and wasting.Possible non-invasive tests,especially breath tests,for components of liver metabolism are discussed.The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients.Additionally,studies in humans are rare,and species differences preclude the transferability of data from rodents to humans.In clinical practice,some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis,but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests.
文摘目的探讨水飞蓟宾治疗初诊2型糖尿病(T2DM)伴非酒精性脂肪肝(NAFLD)对患者肝纤维化进程、糖脂代谢紊乱的调节效果。方法选取2016年1月—2019年1月湖南省脑科医院收治的93例初诊T2DM伴NAFLD患者作为研究对象,采用随机数字表分为观察组47例和对照组46例。两组患者均采取运动、饮食干预+二甲双胍治疗,观察组同时服用水飞蓟宾治疗;对比两组治疗前后的空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)、三酰甘油(TG)、脂联素、瘦素、白细胞介素-6(IL-6)、超氧化物歧化酶(SOD)、Ⅲ型前胶原肽(Ⅲ-PC)、层黏蛋白(LN)、透明质酸(HA)、肝脏彩超评分及不良反应。结果治疗前,两组FPG、2 h PG、HbA1c、HOMA-IR、TC、TG、脂联素、瘦素、IL-6、SOD、彩超评分、Ⅲ-PC、LN、HA测定值比较,差异无统计学意义(P>0.05);治疗后,两组FPG、2 h PG、HbA1c、HOMA-IR、TC、TG、瘦素、IL-6、彩超评分、Ⅲ-PC、LN、HA较治疗前均降低,脂联素、SOD水平较治疗前均升高(均P<0.05),且观察组的TC、TG、瘦素、IL-6、彩超评分、Ⅲ-PC、LN、HA低于对照组,脂联素、SOD水平高于对照组(均P<0.05);两组不良反应发生率差异无统计学意义(P>0.05)。结论T2DM伴NAFLD患者采用水飞蓟宾联合运动、饮食干预+二甲双胍治疗在良好的控制血糖基础上,还能抑制肝纤维化进程,调节糖脂代谢紊乱,临床效果值得肯定。
基金This work was supported by the National Institutes of Health(NIH)grants(R01DK104656,R01DK080440,R01ES025909,R21AA022482,R21AA024935,R01AA026322 to L.Wang)VA Merit Award(1I01BX002634 to L.Wang)the National Natural Scientific Foundation of China(Grant No.81572443 to L.Wang),VA Merit Award(1I01CX000361 to S.Liangpunsakul),NIH(U01AA021840,R01DK107682,R01AA025208,R21AA024935 to S.Liangpunsakul),US DOD(W81XWH-12-1-0497 to S.Liangpunsakul).
文摘Long non-coding RNAs(lncRNAs)are comprised of RNA transcripts exceeding 200 nucleotides in length but lacking identifiable open reading frames(with rare exceptions).Herein,we highlight emerging evidence demonstrating that lncRNAs are critical regulators of liver metabolic function and diseases.We summarize current knowledges about dysregulated lncRNAs and outline the underlying molecular mechanisms by which lncRNAs control hepatic lipid ad glucose metabolism,as well as cholestatic liver disease.Liver-specific triglyceride regulator(lncLSTR),Lnc18q22.2,steroid RNA activator(SRA),highly upregulated in liver cancer(HULC),metastasis associated in lung adenocarcinoma transcript 1(MALAT1),liver glucokinase repressor(lncLGR),maternally expressed gene 3(MEG3),and H19,lncHR1,lnc-HC,apolipoprotein A1 antisense transcript(APOA1-AS),DYNLRB2-2,and LXR-induced sequence(LeXis)are included in the discussion.
