In:
Biological Chemistry, Walter de Gruyter GmbH, Vol. 404, No. 4 ( 2023-03-28), p. 339-353
Abstract:
Ion channels play an important role for regulation of the exocrine and the endocrine pancreas. This review focuses on the Ca 2+ -regulated K + channel K Ca 3.1, encoded by the KCNN4 gene, which is present in both parts of the pancreas. In the islets of Langerhans, K Ca 3.1 channels are involved in the regulation of membrane potential oscillations characterizing nutrient-stimulated islet activity. Channel upregulation is induced by gluco- or lipotoxic conditions and might contribute to micro-inflammation and impaired insulin release in type 2 diabetes mellitus as well as to diabetes-associated renal and vascular complications. In the exocrine pancreas K Ca 3.1 channels are expressed in acinar and ductal cells. They are thought to play a role for anion secretion during digestion but their physiological role has not been fully elucidated yet. Pancreatic carcinoma, especially pancreatic ductal adenocarcinoma (PDAC), is associated with drastic overexpression of K Ca 3.1. For pharmacological targeting of K Ca 3.1 channels, we are discussing the possible benefits K Ca 3.1 channel inhibitors might provide in the context of diabetes mellitus and pancreatic cancer, respectively. We are also giving a perspective for the use of a fluorescently labeled derivative of the K Ca 3.1 blocker senicapoc as a tool to monitor channel distribution in pancreatic tissue. In summary, modulating K Ca 3.1 channel activity is a useful strategy for exo-and endocrine pancreatic disease but further studies are needed to evaluate its clinical suitability.
Type of Medium:
Online Resource
ISSN:
1431-6730
,
1437-4315
DOI:
10.1515/hsz-2022-0232
Language:
English
Publisher:
Walter de Gruyter GmbH
Publication Date:
2023
detail.hit.zdb_id:
1466062-3
SSG:
12
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