Lipid rafts are microdomains in the cell membrane that are involved in cell signal transduction,metabolism,and intercellu-lar interactions.In recent years,studies have shown that lipid rafts play an important role in the pathogenesis of diabetes.Cholesterol and sphingolipids are the main lipid components in lipid rafts,and the protein components in lipid rafts include caveolin,flotillin,pal-mitoylated proteins,and glycosylphosphatidylinositol-anchored proteins.Changes in these components affect the structure and function of lipid rafts,which in turn may affect insulin signal transduction,leading to the occurrence of diabetes-related diseases.Lipid rafts are closely related to the occurrence and development of diabetes in different tissues.Pancreatic lipid rafts are closely related to insulin se-cretion,and their structural changes affect insulin synthesis and release.Changes in lipid rafts in adipose tissue are related to insulin resistance and disorders of glycolipid metabolism.Changes in lipid rafts in the liver can affect gluconeogenesis and glycogen synthesis.Lipid rafts in the kidney play a regulatory role in the progression of diabetic nephropathy.This article aims to provide a comprehensive overview of the role of lipid rafts in the pathogenesis of diabetes,offering insights into the identification of new targets for the prevention and treatment of diabetes in the future,as well as presenting a new perspective for the development of therapeutic agents for diabetes.

Objective:To explore the mechanism of pterostilbene(PTE)in preventing and treating neuroinflamma-tion after cerebral ischemia-reperfusion injury(CIRI)in rats.Methods:Ninety male SD rats were randomly divided in-to a sham group,a model group(MCAO/R),a low-dose PTE group(PTE-L),a medium-dose PTE group(PTE-M),and a high-dose PTE group(PTE-H).CIRI model was prepared by middle cerebral artery occlusion reperfusion(MCAO/R)in rats.The neurological deficit in rats was evaluated by Zea Longa score.The volume of cerebral infarc-tion was detected by TTC staining.The morphological changes of ischemic cortex was observed HE staining.The ex-pressions of cyclooxygenase-2(COX-2),prostaglandin D2 receptor(DP2)and prostaglandin D1 receptor(DP1)were detected by RT-qPCR and Western Blot.The expressions of prostaglandin D2(PGD2),interleukin-1 β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by ELISA.Results:Compared with the sham group,the MCAO/R group showed a significant increase in neurological scores(P＜0.05),a significant increase in cerebral infarction vol-ume(P＜0.05),and aggravated cortical damage in the ischemic area.Additionally,there were significant increase in the expressions of COX-2,DP2 mRNA and protein(P＜0.05),along with increased expressions of PGD2,IL-1β and TNF-α(P＜0.05).Compared with the MCAO/R group,the PTE-L,PTE-M,and PTE-H groups showed a significant decrease in neurological scores(P＜0.05),a significant decrease in cerebral infarction volume(P＜0.05),and markedly alleviated cortical damage in the ischemic region.Additionally,there were significant decrease in the expres-sions of COX-2,DP2 mRNA and protein(P＜0.05),along with decreased expressions of PGD2,IL-1β and TNF-α(P＜0.05).Furthermore,a dose-effect relationship was observed for the neuroprotective effects of PTE on brain tissue(P＜0.05).However,there were no significant differences in the expressions of DP,mRNA and protein among all groups(P＞0.05).Conclusion:PTE can attenuate the neuroinflammation of CIRI in rats by inhibiting COX-2/PGD2/DP2 signaling pathway.

Objective:To explore the mechanism of pterostilbene(PTE)in preventing and treating neuroinflamma-tion after cerebral ischemia-reperfusion injury(CIRI)in rats.Methods:Ninety male SD rats were randomly divided in-to a sham group,a model group(MCAO/R),a low-dose PTE group(PTE-L),a medium-dose PTE group(PTE-M),and a high-dose PTE group(PTE-H).CIRI model was prepared by middle cerebral artery occlusion reperfusion(MCAO/R)in rats.The neurological deficit in rats was evaluated by Zea Longa score.The volume of cerebral infarc-tion was detected by TTC staining.The morphological changes of ischemic cortex was observed HE staining.The ex-pressions of cyclooxygenase-2(COX-2),prostaglandin D2 receptor(DP2)and prostaglandin D1 receptor(DP1)were detected by RT-qPCR and Western Blot.The expressions of prostaglandin D2(PGD2),interleukin-1 β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by ELISA.Results:Compared with the sham group,the MCAO/R group showed a significant increase in neurological scores(P＜0.05),a significant increase in cerebral infarction vol-ume(P＜0.05),and aggravated cortical damage in the ischemic area.Additionally,there were significant increase in the expressions of COX-2,DP2 mRNA and protein(P＜0.05),along with increased expressions of PGD2,IL-1β and TNF-α(P＜0.05).Compared with the MCAO/R group,the PTE-L,PTE-M,and PTE-H groups showed a significant decrease in neurological scores(P＜0.05),a significant decrease in cerebral infarction volume(P＜0.05),and markedly alleviated cortical damage in the ischemic region.Additionally,there were significant decrease in the expres-sions of COX-2,DP2 mRNA and protein(P＜0.05),along with decreased expressions of PGD2,IL-1β and TNF-α(P＜0.05).Furthermore,a dose-effect relationship was observed for the neuroprotective effects of PTE on brain tissue(P＜0.05).However,there were no significant differences in the expressions of DP,mRNA and protein among all groups(P＞0.05).Conclusion:PTE can attenuate the neuroinflammation of CIRI in rats by inhibiting COX-2/PGD2/DP2 signaling pathway.

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an important regulator of plasma asymmetric dimethylarginine (ADMA) levels, which are associated with insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). To elucidate the role of hepatic DDAH1 in the pathogenesis of NAFLD, we used hepatocyte-specific Ddah1-knockout mice (Ddah1^HKO) to examine the progress of high-fat diet (HFD)-induced NAFLD. Compared to diet-matched flox/flox littermates (Ddah1^f/f), Ddah1^HKO mice exhibited higher serum ADMA levels. After HFD feeding for 16 weeks, Ddah1^HKO mice developed more severe liver steatosis and worse insulin resistance than Ddah1^f/f mice. On the contrary, overexpression of DDAH1 attenuated the NAFLD-like phenotype in HFD-fed mice and ob/ob mice. RNA-seq analysis showed that DDAH1 affects NF-κB signaling, lipid metabolic processes, and immune system processes in fatty livers. Furthermore, DDAH1 reduces S100 calcium-binding protein A11 (S100A11) possibly via NF-κB, JNK and oxidative stress-dependent manner in fatty livers. Knockdown of hepatic S100a11 by an AAV8-shS100a11 vector alleviated hepatic steatosis and insulin resistance in HFD-fed Ddah1^HKO mice. In summary, our results suggested that the liver DDAH1/S100A11 axis has a marked effect on liver lipid metabolism in obese mice. Strategies to increase liver DDAH1 activity or decrease S100A11 expression could be a valuable approach for NAFLD therapy.