The oral glucose tolerance test(OGTT)has been widely used both in clinics and in basic research for a long time.It is applied to diagnose impaired glucose tolerance and/or type 2 diabetes mellitus in individuals.Addit...The oral glucose tolerance test(OGTT)has been widely used both in clinics and in basic research for a long time.It is applied to diagnose impaired glucose tolerance and/or type 2 diabetes mellitus in individuals.Additionally,it has been employed in research to investigate glucose utilization and insulin sensitivity in animals.The main aim of each was quite different,and the details are also somewhat varied.However,the time or duration of the OGTT was the same,using the 2-h post-glucose load glycemia in both,following the suggestions of the American Diabetes Association.Recently,the use of 30-min or 1-h post-glucose load glycemia in clinical practice has been recommended by several studies.In this review article,we describe this new view and suggest perspectives for the OGTT.Additionally,quantification of the glucose curve in basic research is also discussed.Unlike in clinical practice,the incremental area under the curve is not suitable for use in the studies involving animals receiving repeated treatments or chronic treatment.We discuss the potential mechanisms in detail.Moreover,variations between bench and bedside in the application of the OGTT are introduced.Finally,the newly identified method for the OGTT must achieve a recommendation from the American Diabetes Association or another official unit soon.In conclusion,we summarize the recent reports regarding the OGTT and add some of our own perspectives,including machine learning and others.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
Cereal straw,a human inedible crop byproduct,can be used as a roughage source in ruminants.However,the nutrition density and palatability are very low,limiting its efficient utilization in animal production.This revie...Cereal straw,a human inedible crop byproduct,can be used as a roughage source in ruminants.However,the nutrition density and palatability are very low,limiting its efficient utilization in animal production.This review aims to systematically provide an overview of the limitations of cereal straws,which is crucial for developing new strategies to enhance the efficient use of cereal straws by lactating dairy cows.Evolutionary molecular biology makes it possible to comprehensively understand the limitations of using cereal straw as a roughage source in dairy cows by different techniques,e.g.,multi-omics.Main constraints for utilization of cereal straw and stover in lactating dairy cows include low contents of easily fermented carbohydrates(pectin)and essential amino acids(Met,Phe,and branched-chain amino acids),high content of lignin and silica,and low nutrient digestibility.These cause insufficient supply of the precursors for milk synthesis and result in increased loss of nutrients in feces and urine.Several molecular mechanisms are revealed by multi-omics techniques,including changed amino acid and glucose metabolism,altered rumen microbial composition and function,and differential expression of miRNAs,mRNA,and protein in multi-organs that are associated with milk synthesis.These can be targets of approaches to improve the utilization of cereal straw by dairy cows.In addition,much attention should be given to the efficient countermeasures,including pretreatments by fibrolytic enzymes or steam explosion,dietary formulations such as supplement of pectin,methionine,and branched-chain amino acids,and feeding with other functional feedstuffs,which may improve the feeding and economic value of cereal straw for lactating dairy cows.The newly revealed functional genes(such as BAG3 in the rumen,PC in the liver,CSN1S2 in the mammary gland)and biomarkers(hippuric acid)as well as the integrative signaling and metabolic pathways(phenylalanine metabolism)related to the shortages of cereal straws could be used as nutritional or genetic regulatory targets to improve dairy cow production.展开更多
Pyruvate dehydrogenase kinases(PDKs)-pyruvate dehydrogenase E1αsubunit(PDHE1α)axis plays an important role in regulating glucose metabolism in mammals.However,the regulatory function of PDKsPDHE1α axis in the gluco...Pyruvate dehydrogenase kinases(PDKs)-pyruvate dehydrogenase E1αsubunit(PDHE1α)axis plays an important role in regulating glucose metabolism in mammals.However,the regulatory function of PDKsPDHE1α axis in the glucose metabolism of fish is not well known.This study determined whether PDKs inhibition could enhance PDHE1αactivity,and improve glucose catabolism in fish.Nile tilapia fingerlings(1.90±0.11 g)were randomly divided into 4 treatments in triplicate(30 fish each)and fed control diet without dichloroacetate(DCA)(38% protein,7% lipid and 45% corn starch)and the control diet supplemented with DCA,which inhibits PDKs through binding the allosteric sites,at 3.75(DCA3.75),7.50(DCA7.50)and 11.25 g/kg(DCA11.25),for 6 wk.The results showed that DCA3.75,DCA7.50 and DCA11.25significantly increased weight gain,carcass ratio and protein efficiency ratio(P<0.05)and reduced feed efficiency(P<0.05)of Nile tilapia.To investigate the effects of DCA on growth performance of Nile tilapia,we selected the lowest dose DCA3.75 for subsequent analysis.Nile tilapia fed on DCA3.75significantly reduced the mesenteric fat index,serum and liver triglyceride concentration and total lipid content in whole fish,and down-regulated the expressions of genes related to lipogenesis(P<0.05)compared to the control.The DCA3.75 treatment significantly improved glucose oxidative catabolism and glycogen synthesis in the liver,but significantly reduced the conversion of glucose to lipid(P<0.05).Furthermore,the DCA3.75 treatment significantly decreased the PDK2/4 gene and protein expressions(P<0.05),accordingly stimulated PDHE1αactivity by decreasing the phosphorylated PDHE1αprotein level.In addition,DCA3.75 treatment significantly increased the phosphorylated levels of key proteins involved in insulin signaling pathway and glycogen synthase kinase 3β(P<0.05).Taken together,the present study demonstrates that PDK2/4 inhibition by using DCA promotes glucose utilization in Nile tilapia by activating PDHE1αand improving insulin sensitivity.Our study helps to understand the regulatory mechanism of glucose metabolism for improving dietary carbohydrate utilization in farmed fish.展开更多
文摘The oral glucose tolerance test(OGTT)has been widely used both in clinics and in basic research for a long time.It is applied to diagnose impaired glucose tolerance and/or type 2 diabetes mellitus in individuals.Additionally,it has been employed in research to investigate glucose utilization and insulin sensitivity in animals.The main aim of each was quite different,and the details are also somewhat varied.However,the time or duration of the OGTT was the same,using the 2-h post-glucose load glycemia in both,following the suggestions of the American Diabetes Association.Recently,the use of 30-min or 1-h post-glucose load glycemia in clinical practice has been recommended by several studies.In this review article,we describe this new view and suggest perspectives for the OGTT.Additionally,quantification of the glucose curve in basic research is also discussed.Unlike in clinical practice,the incremental area under the curve is not suitable for use in the studies involving animals receiving repeated treatments or chronic treatment.We discuss the potential mechanisms in detail.Moreover,variations between bench and bedside in the application of the OGTT are introduced.Finally,the newly identified method for the OGTT must achieve a recommendation from the American Diabetes Association or another official unit soon.In conclusion,we summarize the recent reports regarding the OGTT and add some of our own perspectives,including machine learning and others.
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.
基金the National Basic Research Program of the China Ministry of Science and Technology(2011CB100801)the National Natural Science Foundation of China(No.31472121,31729004)the China Agriculture(Dairy)Research System(CARS-36).
文摘Cereal straw,a human inedible crop byproduct,can be used as a roughage source in ruminants.However,the nutrition density and palatability are very low,limiting its efficient utilization in animal production.This review aims to systematically provide an overview of the limitations of cereal straws,which is crucial for developing new strategies to enhance the efficient use of cereal straws by lactating dairy cows.Evolutionary molecular biology makes it possible to comprehensively understand the limitations of using cereal straw as a roughage source in dairy cows by different techniques,e.g.,multi-omics.Main constraints for utilization of cereal straw and stover in lactating dairy cows include low contents of easily fermented carbohydrates(pectin)and essential amino acids(Met,Phe,and branched-chain amino acids),high content of lignin and silica,and low nutrient digestibility.These cause insufficient supply of the precursors for milk synthesis and result in increased loss of nutrients in feces and urine.Several molecular mechanisms are revealed by multi-omics techniques,including changed amino acid and glucose metabolism,altered rumen microbial composition and function,and differential expression of miRNAs,mRNA,and protein in multi-organs that are associated with milk synthesis.These can be targets of approaches to improve the utilization of cereal straw by dairy cows.In addition,much attention should be given to the efficient countermeasures,including pretreatments by fibrolytic enzymes or steam explosion,dietary formulations such as supplement of pectin,methionine,and branched-chain amino acids,and feeding with other functional feedstuffs,which may improve the feeding and economic value of cereal straw for lactating dairy cows.The newly revealed functional genes(such as BAG3 in the rumen,PC in the liver,CSN1S2 in the mammary gland)and biomarkers(hippuric acid)as well as the integrative signaling and metabolic pathways(phenylalanine metabolism)related to the shortages of cereal straws could be used as nutritional or genetic regulatory targets to improve dairy cow production.
基金the financial support provided by the National Key R&D Program of China(2018YFD0900400)。
文摘Pyruvate dehydrogenase kinases(PDKs)-pyruvate dehydrogenase E1αsubunit(PDHE1α)axis plays an important role in regulating glucose metabolism in mammals.However,the regulatory function of PDKsPDHE1α axis in the glucose metabolism of fish is not well known.This study determined whether PDKs inhibition could enhance PDHE1αactivity,and improve glucose catabolism in fish.Nile tilapia fingerlings(1.90±0.11 g)were randomly divided into 4 treatments in triplicate(30 fish each)and fed control diet without dichloroacetate(DCA)(38% protein,7% lipid and 45% corn starch)and the control diet supplemented with DCA,which inhibits PDKs through binding the allosteric sites,at 3.75(DCA3.75),7.50(DCA7.50)and 11.25 g/kg(DCA11.25),for 6 wk.The results showed that DCA3.75,DCA7.50 and DCA11.25significantly increased weight gain,carcass ratio and protein efficiency ratio(P<0.05)and reduced feed efficiency(P<0.05)of Nile tilapia.To investigate the effects of DCA on growth performance of Nile tilapia,we selected the lowest dose DCA3.75 for subsequent analysis.Nile tilapia fed on DCA3.75significantly reduced the mesenteric fat index,serum and liver triglyceride concentration and total lipid content in whole fish,and down-regulated the expressions of genes related to lipogenesis(P<0.05)compared to the control.The DCA3.75 treatment significantly improved glucose oxidative catabolism and glycogen synthesis in the liver,but significantly reduced the conversion of glucose to lipid(P<0.05).Furthermore,the DCA3.75 treatment significantly decreased the PDK2/4 gene and protein expressions(P<0.05),accordingly stimulated PDHE1αactivity by decreasing the phosphorylated PDHE1αprotein level.In addition,DCA3.75 treatment significantly increased the phosphorylated levels of key proteins involved in insulin signaling pathway and glycogen synthase kinase 3β(P<0.05).Taken together,the present study demonstrates that PDK2/4 inhibition by using DCA promotes glucose utilization in Nile tilapia by activating PDHE1αand improving insulin sensitivity.Our study helps to understand the regulatory mechanism of glucose metabolism for improving dietary carbohydrate utilization in farmed fish.
