It is crucial to understand the glucose control within our bodies.Bariatric/metabolic surgeries,including laparoscopic sleeve gastrec-tomy(LSG)and Roux-en-Y gastric bypass(RYGB),provide an avenue for exploring the pot...It is crucial to understand the glucose control within our bodies.Bariatric/metabolic surgeries,including laparoscopic sleeve gastrec-tomy(LSG)and Roux-en-Y gastric bypass(RYGB),provide an avenue for exploring the potential key factors involved in maintaining glucose homeostasis since these surgeries have shown promising results in improving glycemic control among patients with severe type 2 diabetes(T2D).For the first time,a markedly altered population of serum proteins in patients after LSG was discovered and analyzed through proteomics.Apolipoprotein A-IV(apoA-IV)was revealed to be increased dramatically in diabetic obese patients following LSG,and a similar effect was observed in patients after RYGB surgery.Moreover,recombinant apoA-IV protein treatment was proven to enhance insulin secretion in isolated human islets.These results showed that apoA-IV may play a crucial role in gly-cemic control in humans,potentially through enhancing insulin secretion in human islets.ApoA-IV was further shown to enhance energy expenditure and improve glucose tolerance in diabetic rodents,through stimulating glucose-dependent insulin secretion in pancreaticβcells,partially via Gαs-coupled GPCR/cAMP(G protein-coupled receptor/cyclic adenosine monophosphate)signaling.Furthermore,T55-121,truncated peptide 55-121 of apoA-IV,was discovered to mediate the function of apoA-IV.These collective findings contribute to our understanding of the relationship between apoA-IV and glycemic control,highlighting its potential as a biomarker or therapeutic target in managing and improving glucose regulation.展开更多
In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1（ABCA1）, and lecithin： cholesterol acyltransferase（LCAT） in the formation of plasma H...In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1（ABCA1）, and lecithin： cholesterol acyltransferase（LCAT） in the formation of plasma HDL; the generation of aberrant forms of HDL containing mutant apoA-I forms and the role of apoA-IV and apoE in the formation of distinct HDL subpopulations. The biogenesis of HDL requires functional interactions of the ABCA1 with apoA-I（and to a lesser extent with apoE and apoA-IV） and subsequent interactions of the nascent HDL species thus formed with LCAT. Mutations in apoA-I, ABCA1 and LCAT either prevent or impair the formation of HDL and may also affect the functionality of the HDL species formed. Emphasis is placed on three categories of apoA-I mutations. The first category describes a unique bio-engineered apoA-I mutation that disrupts interactions between apoA-I and ABCA1 and generates aberrant prep HDL subpopulations that cannot be converted efficiently to a subpopulations by LCAT. The second category describes natural and bio-engineered apoA-I mutations that generate preβ and small size a4 HDL subpopulations, and are associated with low plasma HDL levels. These phenotypes can be corrected by excess LCAT. The third category describes bio-engineered apoA-I mutations that induce hypertriglyceridemia that can be corrected by excess lipoprotein lipase and also have defective maturation of HDL.The HDL phenotypes described here may serve in the future for diagnosis, prognoses and potential treatment of abnormalities that affect the biogenesis and functionality of HDL.展开更多
基金supported by the National Natural Science Foundation of China(92357302,32170787,and 32100557)the National Key Research and Development Program of China(2018YFA0800700,2023YFA1801103,and 2018YFA0800900)Researches on human islets were supported by the National Natural Science Foundation of Tianjin Municipal Human Resources and Social Security Bureau(XB202011).
文摘It is crucial to understand the glucose control within our bodies.Bariatric/metabolic surgeries,including laparoscopic sleeve gastrec-tomy(LSG)and Roux-en-Y gastric bypass(RYGB),provide an avenue for exploring the potential key factors involved in maintaining glucose homeostasis since these surgeries have shown promising results in improving glycemic control among patients with severe type 2 diabetes(T2D).For the first time,a markedly altered population of serum proteins in patients after LSG was discovered and analyzed through proteomics.Apolipoprotein A-IV(apoA-IV)was revealed to be increased dramatically in diabetic obese patients following LSG,and a similar effect was observed in patients after RYGB surgery.Moreover,recombinant apoA-IV protein treatment was proven to enhance insulin secretion in isolated human islets.These results showed that apoA-IV may play a crucial role in gly-cemic control in humans,potentially through enhancing insulin secretion in human islets.ApoA-IV was further shown to enhance energy expenditure and improve glucose tolerance in diabetic rodents,through stimulating glucose-dependent insulin secretion in pancreaticβcells,partially via Gαs-coupled GPCR/cAMP(G protein-coupled receptor/cyclic adenosine monophosphate)signaling.Furthermore,T55-121,truncated peptide 55-121 of apoA-IV,was discovered to mediate the function of apoA-IV.These collective findings contribute to our understanding of the relationship between apoA-IV and glycemic control,highlighting its potential as a biomarker or therapeutic target in managing and improving glucose regulation.
基金supported by National Institute of Health Grant HL-48739 and HL-68216
文摘In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1（ABCA1）, and lecithin： cholesterol acyltransferase（LCAT） in the formation of plasma HDL; the generation of aberrant forms of HDL containing mutant apoA-I forms and the role of apoA-IV and apoE in the formation of distinct HDL subpopulations. The biogenesis of HDL requires functional interactions of the ABCA1 with apoA-I（and to a lesser extent with apoE and apoA-IV） and subsequent interactions of the nascent HDL species thus formed with LCAT. Mutations in apoA-I, ABCA1 and LCAT either prevent or impair the formation of HDL and may also affect the functionality of the HDL species formed. Emphasis is placed on three categories of apoA-I mutations. The first category describes a unique bio-engineered apoA-I mutation that disrupts interactions between apoA-I and ABCA1 and generates aberrant prep HDL subpopulations that cannot be converted efficiently to a subpopulations by LCAT. The second category describes natural and bio-engineered apoA-I mutations that generate preβ and small size a4 HDL subpopulations, and are associated with low plasma HDL levels. These phenotypes can be corrected by excess LCAT. The third category describes bio-engineered apoA-I mutations that induce hypertriglyceridemia that can be corrected by excess lipoprotein lipase and also have defective maturation of HDL.The HDL phenotypes described here may serve in the future for diagnosis, prognoses and potential treatment of abnormalities that affect the biogenesis and functionality of HDL.
