Urocortin3: Local inducer of somatostatin release and bellwether of beta cell maturity

Flisher, Marcus F.; Shin, Donghan; Huising, Mark O.

doi:10.1016/j.peptides.2022.170748

Cited by 10 publications

(11 citation statements)

References 76 publications

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“…The selected genes in the genome of the resistant population participate in the pathway related to glucose metabolism, which may be one of the reasons for the significant difference in glucose metabolism between resistant ducks and susceptible ducks infected with DHAV-3. Interestingly, the CRHR2 gene is involved in insulin and glucagon secretion [25]. The results further confirmed that glucose metabolism plays a very important role in the process of DHAV-3 infection from the perspective of genomics.…”

Section: Discussionsupporting

confidence: 65%

Selective analysis of resistance and susceptibility to duck hepatitis A virus genotype 3 in Pekin duck

Liang,

Zhang,

Wang

et al. 2023

Animal Research and One Health

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Duck viral hepatitis (DVH), mainly caused by duck hepatitis A virus genotype 3 (DHAV‐3) in China, is an important disease affecting Pekin ducks. Using artificial selection breeding based on genealogical and phenotypic observations, a susceptible line (Z7) and a resistant line (Z8) of Pekin ducks to DHAV‐3 were identified. Here, we performed a genome‐wide analysis to identify selected genes in the genomes of Pekin ducks underlying resistance/susceptible breeding. Following selection, the mortality rate of the Z8 line reduced from 59.2% to 7.8% in the fourth generation (Z8G4), whereas the death rate of the Z7 line increased from 67.5% to 81% in the third generation (Z7G3). Moreover, directed breeding caused the allele frequencies of Z8 and Z7 changing in opposite direction, accompanied by declines in genomic genetic diversity. With the G0 generation as the reference group, a total of 49 selected genes were identified in the Z7‐susceptible population and 109 selected genes in the Z8‐resistant population based on the top 5% FST and PI ratio, and two candidate key genes were further fine‐mapped. Susceptibility selection led to 17 mutations in the LRIG3 gene in the Z7 population (chr1: 169,757,982–169,772,687), and resistance selection led to 134 mutations in the CRHR2 gene in the Z8 population (chr2: 4,190,154–4,273,970). Our results provide new insights into the resistance and susceptibility to DHAV‐3 and lay a theoretical foundation for further research on the mechanism of resistance/susceptibility of Pekin ducks to DHAV‐3.

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Section: Discussionsupporting

confidence: 65%

Selective analysis of resistance and susceptibility to duck hepatitis A virus genotype 3 in Pekin duck

Liang,

Zhang,

Wang

et al. 2023

Animal Research and One Health

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“…5a, f ). mRNA expression analyses of isolated islets showed that the expression of Urocortin 3 (Ucn3) , a marker of mature β-cells and regulator of insulin secretion 39 , was increased in islets from O304-treated db/db mice (Fig. 5g ).…”

Section: Resultsmentioning

confidence: 99%

O304 ameliorates hyperglycemia in mice by dually promoting muscle glucose effectiveness and preserving β-cell function

Norlin,

Axelsson,

Ericsson

et al. 2023

Commun Biol

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Although insulin mediated glucose uptake in skeletal muscle is a major mechanism ensuring glucose disposal in humans, glucose effectiveness, i.e., the ability of glucose itself to stimulate its own uptake independent of insulin, accounts for roughly half of the glucose disposed during an oral glucose tolerance test. Both insulin dependent and insulin independent skeletal muscle glucose uptake are however reduced in individuals with diabetes. We here show that AMPK activator O304 stimulates insulin independent glucose uptake and utilization in skeletal muscle and heart in vivo, while preventing glycogen accumulation. Combined glucose uptake and utilization requires an increased metabolic demand and we show that O304 acts as a mitochondrial uncoupler, i.e., generates a metabolic demand. O304 averts gene expression changes associated with metabolic inflexibility in skeletal muscle and heart of diabetic mice and reverts diabetic cardiomyopathy. In Type 2 diabetes, insulin resistance elicits compensatory insulin hypersecretion, provoking β-cell stress and eventually compensatory failure. In db/db mice O304 preserves β-cell function by preventing decline in insulin secretion, β-cell mass, and pancreatic insulin content. Thus, as a dual AMPK activator and mitochondrial uncoupler O304 mitigates two central defects of T2D; impaired glucose uptake/utilization and β-cell failure, which today lack effective treatment.

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“…传统观点认为，β细胞凋亡是导致胰岛素分泌不足的主要原因，然而2型糖尿病患者β细胞凋亡程度与胰岛功能衰退程度不成比例［ 16 ］，提示尚存在其他引起β细胞GSIS功能障碍机制。近年文献报道，β细胞去分化是导致2型糖尿病β细胞GSIS功能衰竭的重要原因［ 17 - 19 ］，在2型糖尿病患者及动物模型中均发现成熟胰岛β细胞特异性标志蛋白表达下降，失去正常GSIS功能［ 20 - 21 ］。Ucn3是β细胞成熟和健康的标志［ 22 - 23 ］，本文资料显示，2型糖尿病体内、体外模型中胰岛Ucn3表达下降，提示β细胞成熟度降低，而积雪草酸可增加Ucn3表达，有效改善β细胞成熟度，由此提高β细胞GSIS功能。…”

Section: 讨论unclassified

Asiatic acid improves insulin secretion of cells in type 2 diabetes through TNF-/Mfn2 pathway

Li¹,

Wang²,

Xu³

et al. 2023

J Zhejiang Univ (Med Sci)

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目的研究积雪草酸改善2型糖尿病β细胞功能的作用及分子机制。方法利用高脂饲料和链脲佐菌素构建2型糖尿病小鼠模型，评估不同浓度积雪草酸对2型糖尿病小鼠血糖调节作用，筛选积雪草酸最佳治疗浓度。体外采用棕榈酸处理小鼠胰岛构建2型糖尿病胰岛模型。针对积雪草酸处理后体内、外胰岛模型，利用酶联免疫吸附试验检测胰岛β细胞葡萄糖刺激的胰岛素分泌（GSIS）功能、胰岛内肿瘤坏死因子（TNF）α、白介素（IL）6含量，紫外分光光度法检测胰岛内腺苷三磷酸（ATP）含量，蛋白质印迹法检测胰岛β细胞成熟标志蛋白尿皮质素（Ucn）3及线粒体融合蛋白（Mfn）2表达变化。采用小干扰RNA干扰Mfn2或加用TNF-α处理胰岛后，考察积雪草酸对Ucn3表达及GSIS功能的调控作用。结果体内实验显示，25 mg·kg －1 ·d －1 积雪草酸具有较好的降糖效果，并改善稳态模型评价β细胞指数。积雪草酸可增加Mfn2和Ucn3蛋白表达，改善体内、外糖尿病模型β细胞GSIS功能（均 P <0.05）。体外实验显示，积雪草酸可改善2型糖尿病胰岛ATP生成量（ P <0.05）；干扰Mfn2阻断积雪草酸对Ucn3和GSIS的上调作用。积雪草酸可抑制糖尿病胰岛TNF-α生成（ P <0.05），逆转TNF-α所导致的Mfn2及Ucn3蛋白表达下调。结论积雪草酸能改善2型糖尿病β细胞胰岛素分泌功能，其机制可能与调控TNF-α/Mfn2通路维持β细胞成熟有关。

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Urocortin3: Local inducer of somatostatin release and bellwether of beta cell maturity

Cited by 10 publications

References 76 publications

Selective analysis of resistance and susceptibility to duck hepatitis A virus genotype 3 in Pekin duck

Selective analysis of resistance and susceptibility to duck hepatitis A virus genotype 3 in Pekin duck

O304 ameliorates hyperglycemia in mice by dually promoting muscle glucose effectiveness and preserving β-cell function

Asiatic acid improves insulin secretion of cells in type 2 diabetes through TNF-/Mfn2 pathway

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