Inhibition of protein Kinase C- α and activation of ezrin by < em > Lactobacillus < /em > < em > acidophilus < /em > restore Na < sup > + < /sup > /H < sup > + < /sup > exchange activity and fluid absorption in < em > db/db < /em > mice

In this study, we investigated whether NHE3 expression is altered in type 2 diabetic intestine and the underlying mechanism that dysregulates NHE3. NHE3 expression in the brush border membrane (BBM) of the intestine of diabetic mice and humans was decreased. Protein kinase C (PKC) activation is associated with pathologies of diabetes and immunofluorescence analysis revealed increased BBM PKCα abundance. Inhibition of PKCα increased NHE3 BBM abundance and NHE3-mediated intestinal fluid absorption in db/db mice. Previous studies have shown that Lactobacillus acidophilus (LA) stimulates intestinal ion transporters. LA increased NHE3 BBM expression and mitigated metformin-mediated inhibition of NHE3 in vitro and in vivo. To understand the underlying mechanism of LA mediated stimulation of NHE3, we used Caco-2bbe cells overexpressing PKCa that mimic the elevated state of PKCα in T2D. LA diminished PKCα BBM expression, increased phosphorylation of ezrin, and the interaction of NHE3 with NHE regulatory factor 2 (NHERF2). In addition, inhibition of PKCi blocked phosphorylation of ezrin and activation of NHE3 by LA. These findings demonstrate that NHE3 is downregulated in T2D, and LA restores NHE3 expression via regulation of PKCα, PKCi, and ezrin.PMID:37467022 | DOI:10.1152/ajpendo.00145.2023
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Source Type: research