In:
The FASEB Journal, Wiley, Vol. 33, No. 12 ( 2019-12), p. 14760-14771
Abstract:
Chronic islet inflammation is associated with development of type 2 diabetes mellitus (T2DM). Intermediate‐conductance calcium‐activated K+ (K Ca 3.1) channel plays an important role in inflammatory diseases. However, the role and regulation of K Ca 3.1 in pancreatic β cells in progression of T2DM remain unclarified. In the present study, we evaluated the effect of the specific K Ca 3.1 channel blocker 1‐[(2‐chlorophenyl)diphenylmethyl]‐1H‐pyrazole (TRAM‐34) on diabetic phenotype in the db/db model. In diabetic mice, blockade of K Ca 3.1 significantly improved glucose tolerance, enhanced secretion of postprandial insulin level, and reduced loss of β‐cell mass through attenuating the expression and secretion of inflammatory mediators. Furthermore, in cultured pancreatic β cells, exposure to high levels of glucose or palmitic acid significantly increased expression and current density of the K Ca 3.1 channel as well as secretion of proinflammatory chemokines, and the effects were similarly reversed by preincubation with TRAM‐34 or a NF‐κB inhibitor pyrrolidinedithiocarbamate. Additionally, expression of K Ca 3.1 in pancreas islet cells was up‐regulated by activation of NF‐κBwithIL‐1β stimulation. In summary, up‐regulated K Ca 3.1 due to activation of NF‐κB pathway leads to pancreatic inflammation via expression and secretion of chemokines and cytokines by pancreatic β cells, thereby facilitating progression of T2DM.—Pang, Z.‐D., Wang, Y., Wang, X.‐J., She, G., Ma, X.‐Z., Song, Z., Zhao, L.‐M., Wang, H.‐F., Lai, B.‐C., Gou, W., Du, X.‐J., Deng, X.‐L. K Ca 3.1 channel mediates inflammatory signaling of pancreatic β cells and progression of type 2 diabetes mellitus. FASEB J. 33, 14760‐14771 (2019). www.fasebj.org
Type of Medium:
Online Resource
ISSN:
0892-6638
,
1530-6860
DOI:
10.1096/fj.201901329RR
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
1468876-1
SSG:
12
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