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Role of CFTR in diabetes-induced pancreatic ductal fluid and HCO3− secretion
The Journal of Physiology ( IF 5.5 ) Pub Date : 2024-02-22 , DOI: 10.1113/jp285702
Attila Ébert 1, 2 , Eleonóra Gál 1 , Emese Tóth 3, 4 , Titanilla Szögi 5 , Péter Hegyi 3, 6, 7, 8 , Viktória Venglovecz 1, 6
Affiliation  

Type 1 diabetes is a disease of the endocrine pancreas; however, it also affects exocrine function. Although most studies have examined the effects of diabetes on acinar cells, much less is known regarding ductal cells, despite their important protective function in the pancreas. Therefore, we investigated the effect of diabetes on ductal function. Diabetes was induced in wild-type and cystic fibrosis transmembrane conductance regulator (CFTR) knockout mice following an i.p. administration of streptozotocin. Pancreatic ductal fluid and HCO3 secretion were determined using fluid secretion measurements and fluorescence microscopy, respectively. The expression of ion transporters was measured by real-time PCR and immunohistochemistry. Transmission electron microscopy was used for the morphological characterization of the pancreas. Serum secretin and cholecystokinin levels were measured by an enzyme-linked immunosorbent assay. Ductal fluid and HCO3 secretion, CFTR activity, and the expression of CFTR, Na+/H+ exchanger-1, anoctamine-1 and aquaporin-1 were significantly elevated in diabetic mice. Acute or chronic glucose treatment did not affect HCO3 secretion, but increased alkalizing transporter activity. Inhibition of CFTR significantly reduced HCO3 secretion in both normal and diabetic mice. Serum levels of secretin and cholecystokinin were unchanged, but the expression of secretin receptors significantly increased in diabetic mice. Diabetes increases fluid and HCO3 secretion in pancreatic ductal cells, which is associated with the increased function of ion and water transporters, particularly CFTR.
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中文翻译:

CFTR 在糖尿病引起的胰管液和 HCO3− 分泌中的作用

1 型糖尿病是一种内分泌胰腺疾病;然而,它也会影响外分泌功能。尽管大多数研究都研究了糖尿病对腺泡细胞的影响,但对于导管细胞的了解却少之又少,尽管它们在胰腺中具有重要的保护功能。因此,我们研究了糖尿病对导管功能的影响。野生型和囊性纤维化跨膜电导调节因子 (CFTR) 敲除小鼠腹腔注射脲佐菌素后诱发糖尿病。分别使用液体分泌测量和荧光显微镜测定胰管液和HCO 3 -分泌。通过实时PCR和免疫组织化学测量离子转运蛋白的表达。透射电子显微镜用于胰腺的形态学表征。通过酶联免疫吸附测定法测量血清促胰液素和胆囊收缩素水平。糖尿病小鼠的导管液和HCO 3 -分泌、CFTR活性以及CFTR、Na + /H +交换器-1、anoctamine-1和aquaporin-1的表达显着升高。急性或慢性葡萄糖治疗不影响HCO 3 -分泌,但增加碱化转运蛋白活性。抑制CFTR可显着减少正常小鼠和糖尿病小鼠的HCO 3 -分泌。糖尿病小鼠的血清促胰液素和胆囊收缩素水平没有变化,但促胰液素受体的表达显着增加。糖尿病会增加胰腺导管细胞中的液体和 HCO 3 -分泌,这与离子和水转运蛋白(尤其是 CFTR)功能的增强有关。
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更新日期:2024-02-22
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