Insulin resistance is a condition in which the target tissues have a decreased response to insulin signaling,resulting in glucose uptake defect,and an increased blood sugar level.Pancreatic beta cells thus enhance ins...Insulin resistance is a condition in which the target tissues have a decreased response to insulin signaling,resulting in glucose uptake defect,and an increased blood sugar level.Pancreatic beta cells thus enhance insulin production to compensate.This situation may cause further beta cell dysfunction and failure,which can lead diabetes mellitus(DM).Insulin resistance is thus an important cause of the development of type 2 DM.Insulin resistance has also been found to have a strong relationship with cardiovascular disease and is common in chronic kidney disease(CKD)patients.The mechanisms of insulin resistance in CKD are complex and multifactorial.They include physical inactivity,inflammation and oxidative stress,metabolic acidosis,vitamin D deficiency,adipose tissue dysfun-ction,uremic toxins,and renin-angiotensin-aldosterone system activation.Currently,available anti-diabetic agents,such as biguanides,sulfonylureas,thiazolidinediones,alfa-glucosidase inhibitors,glucagon-like peptide-1-based agents,and sodium-glucose co-transporter-2 inhibitors,have different effects on insulin resistance.In this short review,we describe the potential mechanisms of insulin resistance in CKD patients.We also review the interaction of currently available anti-diabetic medications with insulin resistance.展开更多
Over the last several hundred years,donkeys have adapted to high-altitude conditions on the Tibetan Plateau.Interestingly,the kiang,a closely related equid species,also inhabits this region.Previous reports have demon...Over the last several hundred years,donkeys have adapted to high-altitude conditions on the Tibetan Plateau.Interestingly,the kiang,a closely related equid species,also inhabits this region.Previous reports have demonstrated the importance of specific genes and adaptive introgression in divergent lineages for adaptation to hypoxic conditions on the Tibetan Plateau.Here,we assessed whether donkeys and kiangs adapted to the Tibetan Plateau via the same or different biological pathways and whether adaptive introgression has occurred.We assembled a de novo genome from a kiang individual and analyzed the genomes of five kiangs and 93 donkeys(including 24 from the Tibetan Plateau).Our analyses suggested the existence of a strong hard selective sweep at the EPAS1 locus in kiangs.In Tibetan donkeys,however,another gene,i.e.,EGLN1,was likely involved in their adaptation to high altitude.In addition,admixture analysis found no evidence for interspecific gene flow between kiangs and Tibetan donkeys.Our findings indicate that despite the short evolutionary time scale since the arrival of donkeys on the Tibetan Plateau,as well as the existence of a closely related species already adapted to hypoxia,Tibetan donkeys did not acquire adaptation via admixture but instead evolved adaptations via a different biological pathway.展开更多
文摘Insulin resistance is a condition in which the target tissues have a decreased response to insulin signaling,resulting in glucose uptake defect,and an increased blood sugar level.Pancreatic beta cells thus enhance insulin production to compensate.This situation may cause further beta cell dysfunction and failure,which can lead diabetes mellitus(DM).Insulin resistance is thus an important cause of the development of type 2 DM.Insulin resistance has also been found to have a strong relationship with cardiovascular disease and is common in chronic kidney disease(CKD)patients.The mechanisms of insulin resistance in CKD are complex and multifactorial.They include physical inactivity,inflammation and oxidative stress,metabolic acidosis,vitamin D deficiency,adipose tissue dysfun-ction,uremic toxins,and renin-angiotensin-aldosterone system activation.Currently,available anti-diabetic agents,such as biguanides,sulfonylureas,thiazolidinediones,alfa-glucosidase inhibitors,glucagon-like peptide-1-based agents,and sodium-glucose co-transporter-2 inhibitors,have different effects on insulin resistance.In this short review,we describe the potential mechanisms of insulin resistance in CKD patients.We also review the interaction of currently available anti-diabetic medications with insulin resistance.
基金supported by the National Natural Science Foundation of China(31621062)Strategic Priority Research Program of the Chinese Academy of Sciences(XDA2004010302)+4 种基金Second Tibetan Plateau Scientific Expedition and Research(STEP)Program(2019QZKK05010703)supported by the National Natural Science Foundation of China(91731304,31822048)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13020600)Qinghai Department of Science and Technology Major ProjectState Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan,Yunnan University(2018KF001)supported by the Animal Branch of the Germplasm Bank of Wild Species,Chinese Academy of Sciences(Large Research Infrastructure Funding)
文摘Over the last several hundred years,donkeys have adapted to high-altitude conditions on the Tibetan Plateau.Interestingly,the kiang,a closely related equid species,also inhabits this region.Previous reports have demonstrated the importance of specific genes and adaptive introgression in divergent lineages for adaptation to hypoxic conditions on the Tibetan Plateau.Here,we assessed whether donkeys and kiangs adapted to the Tibetan Plateau via the same or different biological pathways and whether adaptive introgression has occurred.We assembled a de novo genome from a kiang individual and analyzed the genomes of five kiangs and 93 donkeys(including 24 from the Tibetan Plateau).Our analyses suggested the existence of a strong hard selective sweep at the EPAS1 locus in kiangs.In Tibetan donkeys,however,another gene,i.e.,EGLN1,was likely involved in their adaptation to high altitude.In addition,admixture analysis found no evidence for interspecific gene flow between kiangs and Tibetan donkeys.Our findings indicate that despite the short evolutionary time scale since the arrival of donkeys on the Tibetan Plateau,as well as the existence of a closely related species already adapted to hypoxia,Tibetan donkeys did not acquire adaptation via admixture but instead evolved adaptations via a different biological pathway.
