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- Lai, Enyin, et al.
(författare)
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Blood lipids affect rat islet blood flow regulation through beta(3)-adrenoceptors
- 2014
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 307:8, s. E653-E663
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic islet blood perfusion varies according to the needs for insulin secretion. We examined the effects of blood lipids on pancreatic islet blood flow in anesthetized rats. Acute administration of Intralipid to anesthetized rats increased both triglycerides and free fatty acids, associated with a simultaneous increase in total pancreatic and islet blood flow. A preceding abdominal vagotomy markedly potentiated this and led acutely to a 10-fold increase in islet blood flow associated with a similar increase in serum insulin concentrations. The islet blood flow and serum insulin response could be largely prevented by pretreatment with propranolol and the selective beta(3)-adrenergic inhibitor SR-59230A. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester prevented the blood flow increase but was less effective in reducing serum insulin. Increased islet blood flow after Intralipid administration was also seen in islet and whole pancreas transplanted rats, i.e., models with different degrees of chronic islet denervation, but the effect was not as pronounced. In isolated vascularly perfused single islets Intralipid dilated islet arterioles, but this was not affected by SR-59230A. Both the sympathetic and parasympathetic nervous system are important for the coordination of islet blood flow and insulin release during hyperlipidemia, with a previously unknown role for beta(3)-adrenoceptors.
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| 2. |
- Lai, Enyin, 1965-
(författare)
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Interaction between Adenosine and Angiotensin II in Renal Afferent Arterioles of Mice
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Renal arterioles represent the most important effecter site in the control of renal perfusion and filtration. Adenosine (Ado), angiotensin II (Ang II) and nitric oxide (NO) interact in modulating arteriolar tone. The present work investigates the mechanism of this interaction. We tested the hypothesis that AT1 receptor (AT1AR) mediated NO release in isolated perfused afferent arterioles. Further, special attention was given to mechanisms of Ado-Ang II -interactions. We found (I) that Ang II specifically induces NO release via AT1AR in arterioles. The effect is important in view of high renin and Ang II concentrations in these vessels. (II) Ado modulates the Ang II response by acting on vasoconstrictor A1AR and vasodilator A2AR. Vice versa, Ang II critically enhances the constriction to Ado, which supports the assumption of its modulating action in the tubuloglomerular feedback (TGF). (III) The synergistic effect of Ang II and Ado on arteriolar contraction is concurrent with an increase in the cytosolic calcium. Further, (IV) Ado increases the calcium sensitivity of the contractile machinery in arteriolar smooth muscle cells most probably by enhancement of the phosphorylation of the myosin light chain regulatory unit. RhoA kinase, protein kinase C and p38 MAP are involved in the Ado effect, which is not receptor mediated and depends on the Ado uptake into vascular cells. Remarkably, the enhancing action of Ado is most likely limited to Ang II; since Ado does not influence endothelin-1 and norepinephrine induced contractions. These novel results extend our knowledge about the synergistic action of Ang II and Ado in the control of renal filtration. Ado, the key factor in mediation of the TGF, develops a significant vasoconstrictor action only in the presence of Ang II. On the other hand, the Ang II induced vasoconstriction is modulated by Ado via receptor and non-receptor mediated intracellular signaling pathways.
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| 4. |
- Liu, Yu, et al.
(författare)
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Diagnostic Values of METTL1-Related Genes and Immune Characteristics in Systemic Lupus Erythematosus
- 2023
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Ingår i: Journal of Inflammation Research. - : Dove Medical Press. - 1178-7031. ; 16, s. 5367-5383
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Methyltransferase like 1 (METTL1) regulates epitranscriptomes via the m7G modification in mammalian mRNA and microRNA. Systemic lupus erythematosus (SLE) is caused by abnormal immune reactivity and has diverse clinical manifestations. RNA methylation as a mechanism to regulate gene expression is widely implicated in immune regulation. However, the role of m7G in immune response of SLE has not been extensively studied.Patients and Methods: Expression of METTL1 was identified in the public dataset GSE122459 and validated in an independent cohort of SLE patients. We investigated the association between METTL1-expression and clinical manifestations of SLE. Subsequently, differentially expressed genes (DEG) that were correlated with METTL1-expression in GSE122459 were used for functional enrichment analysis. The correlation between infiltrating immune cells and METTL1, as well as candidate biomarkers identified to be correlated with either METTL1 or immune cell infiltration were assessed by single-sample GSEA. Potential mechanisms were explored with Gene ontology and KEGG pathway enrichment. Diagnostic performances of candidate biomarkers in SLE were analyzed.Results: The mRNA and protein expression of METTL1 in SLE patients were significantly decreased in both datasets. METTL1-coexpressed DEGs were enriched in several key immune-related pathways. Activated CD8 T cells, activated CD4 T cells, memory B cells and type 2 helper T cells were different between patients with high and low METTL1 expression. Further, activated CD8 T-cells, activated CD4 T-cells, memory B-cells were correlated with METTL1. The genes of LAMP3, CD83, PDCD1LG2, IGKVD3D-20, IGKV5-2, IGKV2D-30, IGLV3-19 and IGLV4-60 were identified as candidate targets that were correlated with immune cell proportion. Moreover, LAMP3, CD83, and PDCD1LG2 expression were of diagnostic value in SLE as indicated by ROC analysis.Conclusion: Our findings suggested that METTL1 and its candidate targets LAMP3, CD83, PDCD1LG2 may be used for diagnosing SLE and could be explored for developing targeted molecular therapy for SLE.
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| 8. |
- Wang, Zhongli, et al.
(författare)
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Sex-specific prevalence of fatty liver disease and associated metabolic factors in Wuhan, south central China
- 2014
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Ingår i: European Journal of Gastroenterology and Hepathology. - 0954-691X .- 1473-5687. ; 26:9, s. 1015-1021
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Tidskriftsartikel (refereegranskat)abstract
- Background This study aimed to investigate the sex-specific prevalence and metabolic risk factors of fatty liver disease (FLD), and to predict the prevalence of steatohepatitis with liver fibrosis in Wuhan, south central China. Methods A cross-sectional study was conducted among 25 032 participants who underwent health checkups from 2010 to 2011 in Zhongnan hospital. Results The prevalence of FLD was higher among men than among women (31.8 vs. 12.9%, P<0.0001). However, it increased markedly with age among women, and in the age-groups above 60 years, the prevalence was similar between men and women (26.4 vs. 27.6%, P>0.05). FLD was associated with obesity, increased levels of total cholesterol, triglycerides (TG), low-density lipoproteins, serum uric acid, aspartate aminotransferase, alanine aminotransferase, and fasting blood sugar, an aspartate aminotransferase/alanine aminotransferase ratio of less than 1, and a decreased level of high-density lipoprotein in both sexes. Multiple regression analyses showed that obesity, elevated levels of fasting blood sugar, TG, total cholesterol, and alanine aminotransferase, an aspartate aminotransferase/alanine aminotransferase ratio of less than 1, serum uric acid levels, and decreased high-density lipoprotein levels were related to FLD in men, whereas age played a more prominent role in women. The prevalence of steatohepatitis with advanced fibrosis, estimated using the BMI, age, ALT, and TG index (BAAT index), was 2.5% in men and 1.4% in women; more women with FLD had a BAAT score of 3 or higher compared with men (9.0 vs. 6.6%). Conclusion The prevalence of FLD in China is high among men and elderly women and is mainly related to various metabolic parameters. The prevalence of steatohepatitis with advanced fibrosis is considerably high among individuals with FLD.
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