Insulin and the phosphatidylinositol 3-kinase signaling pathway regulate Ribonuclease 7 expression in the human urinary tract

Tad E. Eichler, Brian Becknell, Robert S. Easterling, Susan E. Ingraham, Daniel M. Cohen, Andrew L. Schwaderer, David Hains, Birong Li, Ariel Cohen, Jackie Metheny, Susheela Tridandapani, John David Spencer

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Diabetes mellitus is a systemic disease associated with a deficiency of insulin production or action. Diabetic patients have an increased susceptibility to infection with the urinary tract being the most common site. Recent studies suggest that Ribonuclease 7 (RNase 7) is a potent antimicrobial peptide that plays an important role in protecting the urinary tract from bacterial insult. Because the impact of diabetes on RNase 7 expression and function are unknown, we investigated the effects of insulin on RNase 7 using human urine specimens. The urinary RNase 7 concentrations were measured in healthy control patients and insulin-deficient type 1 diabetics before and after starting insulin therapy. Compared with controls, diabetic patients had suppressed urinary RNase 7 concentrations, which increased with insulin. Using primary human urothelial cells, the mechanisms by which insulin stimulates RNase 7 synthesis were next explored. Insulin induced RNase 7 production via the phosphatidylinositide 3-kinase signaling pathway (PI3K/AKT) to shield urothelial cells from uropathogenic E. coli. In contrast, uropathogenic E. coli suppressed PI3K/AKT activity and RNase 7 production. Thus, insulin and PI3K/AKT signaling are essential for RNase 7 expression and increased infection risks in diabetic patients may be secondary to suppressed RNase 7 production. Our data may provide unique insight into novel urinary tract infection therapeutic strategies in at-risk populations.

Original languageEnglish (US)
Pages (from-to)568-579
Number of pages12
JournalKidney International
Volume90
Issue number3
DOIs
StatePublished - Sep 1 2016

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Phosphatidylinositol 3-Kinase
Urinary Tract
Insulin
Phosphatidylinositol 3-Kinases
Uropathogenic Escherichia coli
Urinary Tract Infections
Ribonuclease 7
Diabetes Mellitus
Phosphotransferases
Urine

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Eichler, T. E., Becknell, B., Easterling, R. S., Ingraham, S. E., Cohen, D. M., Schwaderer, A. L., ... Spencer, J. D. (2016). Insulin and the phosphatidylinositol 3-kinase signaling pathway regulate Ribonuclease 7 expression in the human urinary tract. Kidney International, 90(3), 568-579. https://doi.org/10.1016/j.kint.2016.04.025

Insulin and the phosphatidylinositol 3-kinase signaling pathway regulate Ribonuclease 7 expression in the human urinary tract. / Eichler, Tad E.; Becknell, Brian; Easterling, Robert S.; Ingraham, Susan E.; Cohen, Daniel M.; Schwaderer, Andrew L.; Hains, David; Li, Birong; Cohen, Ariel; Metheny, Jackie; Tridandapani, Susheela; Spencer, John David.

In: Kidney International, Vol. 90, No. 3, 01.09.2016, p. 568-579.

Research output: Contribution to journalArticle

Eichler, TE, Becknell, B, Easterling, RS, Ingraham, SE, Cohen, DM, Schwaderer, AL, Hains, D, Li, B, Cohen, A, Metheny, J, Tridandapani, S & Spencer, JD 2016, 'Insulin and the phosphatidylinositol 3-kinase signaling pathway regulate Ribonuclease 7 expression in the human urinary tract', Kidney International, vol. 90, no. 3, pp. 568-579. https://doi.org/10.1016/j.kint.2016.04.025
Eichler, Tad E. ; Becknell, Brian ; Easterling, Robert S. ; Ingraham, Susan E. ; Cohen, Daniel M. ; Schwaderer, Andrew L. ; Hains, David ; Li, Birong ; Cohen, Ariel ; Metheny, Jackie ; Tridandapani, Susheela ; Spencer, John David. / Insulin and the phosphatidylinositol 3-kinase signaling pathway regulate Ribonuclease 7 expression in the human urinary tract. In: Kidney International. 2016 ; Vol. 90, No. 3. pp. 568-579.
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