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001-es BibID:	BIBFORM119763
035-os BibID:	(WoS)001169383700001 (Scopus)85186435699
Első szerző:	Ébert Attila
Cím:	Role of CFTR in diabetes-induced pancreatic ductal fluid and HCO3- secretion / Attila Ébert, Eleonóra Gál, Emese Tóth, Titanilla Szögi, Péter Hegyi, Viktória Venglovecz
Dátum:	2024
ISSN:	0022-3751 1469-7793
Megjegyzések:	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.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Journal Of Physiology-London. - 602 : 6 (2024), p. 1065-1083. -
További szerzők:	Gál Eleonóra Tóth Emese (1990-) (molekuláris biológus) Szögi Titanilla Hegyi Péter Venglovecz Viktória
Pályázati támogatás:	NKFIH SNN134497 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM127848
035-os BibID:	(Scopus)85206849180 (WoS)001333699700001
Első szerző:	Venglovecz Viktória
Cím:	Restoring CFTR function with Orkambi decreases the severity of alcohol-induced acute pancreatitis / Viktória Venglovecz, Anna Grassalkovich, Emese Tóth, Attila Ébert, Eleonóra Gál, Marietta Margaréta Korsós, József Maléth, Zoltán Rakonczay, Zsolt Galla, Péter Monostori, Péter Hegyi
Dátum:	2024
ISSN:	0022-3751 1469-7793
Megjegyzések:	Abstract: Heavy alcohol intake is one of the most common causes of acute pancreatitis (AP). We have previously shown that ethanol (EtOH) decreases the expression and activity of the cystic fibrosis transmembrane conductance regulator (CFTR), which plays a key role in alcohol-induced AP development. The prescription drug, Orkambi (a combination of ivacaftor and lumacaftor) can correct impaired CFTR function and expression in cystic fibrosis (CF) patients. Thus, the present study aimed to investigate whether Orkambi can mitigate alcohol-induced AP. Intact guinea-pig pancreatic ducts were pre-treated with different concentrations of ethanol (EtOH; 30, 50 and 100 mm) for 12 h alone or in combination with ivacaftor (VX770) and/or lumacaftor (VX-809), and CFTR expression and activity were evaluated by immunostaining and by the patch clamp technique, respectively. Alcoholic AP was induced in Orkambi-treated guinea-pigs, and standard laboratory and histological parameters were measured. Ivacaftor and lumacaftor alone or in combination dose-dependently restored the apical expression and activity of CFTR after EtOH treatment in vitro. Oral administration of Orkambi reduced the severity of alcohol-induced AP and restored impaired CFTR activity and expression. Orkambi is able to restore the CFTR defect caused by EtOH and decreases the severity of alcohol-induced pancreatitis. This is the first in vivo pre-clinical evidence of Orkambi efficacy in the treatment of alcohol-induced AP. (Figure presented.). Key points: Acute pancreatitis is one of the leading causes of hospital admission among gastrointestinal diseases in which the lack of a specific drug therapy plays a crucial role. The cystic fibrosis transmembrane conductance regulator (CFTR) plays an essential role in pancreatic ductal HCO3-secretion; inappropriate CFTR function, as seen in heavy alcohol consumption, increases the risk of pancreatitis development. CFTR modulators are able to prevent the inhibitory effect of ethanol and reduce pancreatic ductal injury and the severity of alcohol-induced pancreatitis. CFTR modulators present a novel option in the pharmacotherapy of alcohol-induced pancreatitis by enhancing pancreatic functions or preventing recurrence.
Tárgyszavak:	Orvostudományok Egészségtudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk CFTR ethanol Orkambi pancreatitis
Megjelenés:	Journal Of Physiology-London. - 602 : 22 (2024), p. 6153-6170. -
További szerzők:	Grassalkovich Anna Tóth Emese (1990-) (molekuláris biológus) Ébert Attila Gál Eleonóra Korsós Marietta Margaréta Maléth József Rakonczay Zoltán Galla Zsolt Monostori Péter Hegyi Péter
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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