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Angiotensin II type 2 receptor inhibits expression and function of insulin receptor in rat renal proximal tubule cells
- Source :
- Journal of the American Society of Hypertension. 12:135-145
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Both renin–angiotensin systems and insulin participate in kidney-involved blood pressure regulation. Activation of angiotensin II type 2 receptor (AT 2 R) decreases sodium reabsorption in renal proximal tubule (RPT) cells, whereas insulin produces the opposite effect. We presume that AT 2 R has an inhibitory effect on insulin receptor expression in RPT cells, which may affect renal sodium transport and therefore be of physiological or pathological significance. Our present study found that activation of AT 2 R inhibited insulin receptor expression in a concentration and time-dependent manner in RPT cells from Wistar-Kyoto (WKY) rats. In the presence of a protein kinase C (PKC) inhibitor (PKC inhibitor peptide 19–31, 10 −6 mol/L) or a phosphatidylinositol 3 kinase inhibitor (wortmannin, 10 −6 mol/L), the inhibitory effect of AT 2 R on insulin receptor was blocked, indicating that both PKC and phosphatidylinositol 3 kinase were involved in the signaling pathway. There was a linkage between AT 2 R and insulin receptor which was determined by both laser confocal microscopy and coimmunoprecipitation. However, the effect of AT 2 R activation on insulin receptor expression was different in RPT cells from spontaneously hypertensive rats (SHRs). Being contrary to the effect in WKY RPT cells, AT 2 R stimulation increased insulin receptor in SHR RPT cells. Insulin (10 −7 mol/L, 15 minutes) enhanced Na + -K + -ATPase activity in both WKY and SHR RPT cells. Pretreatment with CGP42112 decreased the stimulatory effect of insulin on Na + -K + -ATPase activity in WKY RPT cells, whereas pretreatment with CGP42112 increased it in SHR RPT cells. It is suggested that activation of AT 2 R inhibits insulin receptor expression and function in RPT cells. The lost inhibitory effect of AT 2 R on insulin receptor expression may contribute to the pathophysiology of hypertension.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
medicine.medical_treatment
Blood Pressure
030204 cardiovascular system & hematology
Rats, Inbred WKY
Receptor, Angiotensin, Type 2
Article
Cell Line
Kidney Tubules, Proximal
Renin-Angiotensin System
Wortmannin
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Rats, Inbred SHR
Internal medicine
Internal Medicine
medicine
Animals
Phosphatidylinositol
Protein Kinase Inhibitors
Protein Kinase C
Protein kinase C
Phosphoinositide-3 Kinase Inhibitors
Renal sodium reabsorption
biology
Kinase
business.industry
Insulin
Sodium
Receptor, Insulin
Rats
Renal Elimination
Insulin receptor
030104 developmental biology
Endocrinology
Gene Expression Regulation
chemistry
Hypertension
biology.protein
Phosphatidylinositol 3-Kinase
Sodium-Potassium-Exchanging ATPase
Signal transduction
Cardiology and Cardiovascular Medicine
business
Signal Transduction
Subjects
Details
- ISSN :
- 19331711
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Journal of the American Society of Hypertension
- Accession number :
- edsair.doi.dedup.....0af6f2cfb1df6eddcb9976055bc272d1