Sex differences in soluble prorenin receptor in patients with type 2 diabetes

Abstract Background The soluble prorenin receptor (sPRR), a member of the renin-angiotensin system (RAS), is elevated in plasma of patients with preeclampsia, hypertension, chronic kidney disease (CKD), and type 2 diabetes. Our goal was to examine the relationship between sPRR and RAS activation to define whether sexual dimorphisms in sPRR might explain sex disparities in renal outcomes in patients with type 2 diabetes. Methods Two hundred sixty-nine participants were included in the study (mean age, 48 ± 16 years; 42% men, 58% women), including 173 controls and 96 subjects with type 2 diabetes. In plasma and urine, we measured sPRR, plasma renin activity (PRA), and prorenin. In the urine, we also measured angiotensinogen along with other biomarkers of renal dysfunction. Results Plasma sPRR and PRA were significantly higher in women with type 2 diabetes compared to men. In these women, plasma sPRR was positively correlated with PRA, age, and body mass index (BMI). In contrast, in men the sPRR in urine but not in plasma positively correlated with eGFR in urine, but negatively correlated with urine renin activity, plasma glucose, age, and BMI. Conclusions In patients with type 2 diabetes, sPRR contributes to RAS stimulation in a sex-dependent fashion. In diabetic women, increased plasma sPRR parallels the activation of systemic RAS; while in diabetic men, decreased sPRR in urine matches intrarenal RAS stimulation. sPRR might be a potential indicator of intrarenal RAS activation and renal dysfunction in men and women with type 2 diabetes.

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Abstract 073: The Association Between Plasma Soluble Prorenin Receptor and Renin Activity Points Toward Renin Angiotensin System Activation and Cardiovascular Complications in Women With Type-2 Diabetes

Hypertension ◽

10.1161/hyp.74.suppl_1.073 ◽

2019 ◽

Vol 74 (Suppl_1) ◽

Author(s):

Bruna Visniauskas ◽

Danielle Y Arita ◽

Carla B Rosales ◽

Mohammed A Feroz ◽

John Lefante ◽

...

Keyword(s):

Type 2 Diabetes ◽

Renin Angiotensin System ◽

Cardiovascular Complications ◽

Renin Activity ◽

Angiotensin System ◽

Renin Angiotensin ◽

Prorenin Receptor ◽

System Activation

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Associations between glycaemic control and activation of the renin-angiotensin-aldosterone system in participants with type 2 diabetes mellitus and hypertension

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563217728964 ◽

2017 ◽

Vol 55 (3) ◽

pp. 373-384 ◽

Cited By ~ 3

Author(s):

TP Griffin ◽

D Wall ◽

GA Browne ◽

MC Dennedy ◽

PM O'Shea

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glycaemic Control ◽

Plasma Renin Activity ◽

Linear Correlation ◽

Plasma Renin ◽

Glycated Haemoglobin ◽

Renin Activity

Introduction Hyperglycaemia increases succinate concentrations and succinate receptor activation in the kidney resulting in renin release. The aim of our study was to determine if there is an association between glycaemic control as evidenced by glycated haemoglobin values and activation of the renin-angiotensin-aldosterone system in patients with type 2 diabetes mellitus and hypertension. Methods A cross-sectional study was conducted at Galway University Hospitals between December 2014 and March 2015. Participants ( n = 66) were identified following interrogation of the electronic database for patients with type 2 diabetes mellitus. Baseline clinical demographics, aldosterone, plasma renin activity, direct renin concentration, urea and electrolytes, glycated haemoglobin, cholesterol, urine sodium and albumin creatinine ratio were recorded. Results There was a significant positive linear correlation between glycated haemoglobin and renin (both plasma renin activity [ P = 0.002] and direct renin concentration [ P = 0.008]) and between serum creatinine and aldosterone measured using both radioimmunoassay ( P = 0.008) and immunochemiluminometric assay ( P = 0.008). A significant negative linear correlation was demonstrated between serum sodium and plasma renin activity ( P = 0.005) and direct renin concentration ( P = 0.015) and between estimated glomerular filtration rate and aldosterone measured using radioimmunoassay ( P = 0.02) and immunochemiluminometric assay ( P = 0.016). A significant negative linear correlation existed between urine sodium and plasma renin activity ( P = 0.04) and aldosterone measured using radioimmunoassay ( P = 0.045). Conclusions There is a direct positive association between glycaemic control and renin. We advocate for renin measurement to be part of the diabetologist's armamentarium to assess, guide and optimize therapeutic strategies in patients with diabetes.

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Short-term dietary salt supplementation blunts telmisartan induced increases in plasma renin activity in hypertensive patients with type 2 diabetes mellitus

Clinical Science ◽

10.1042/cs20140536 ◽

2015 ◽

Vol 129 (5) ◽

pp. 415-422 ◽

Cited By ~ 7

Author(s):

Angela X. Chen ◽

George Jerums ◽

Sara Baqar ◽

Elisabeth Lambert ◽

Goji Somarajah ◽

...

Keyword(s):

Type 2 Diabetes ◽

Plasma Renin Activity ◽

Plasma Renin ◽

Renin Activity ◽

Angiotensin Ii Receptor Blocker ◽

Angiotensin Ii Receptor ◽

Dietary Salt ◽

Short Term ◽

Serum Aldosterone

In patients with type 2 diabetes, this study demonstrates that short-term dietary salt supplementation significantly blunts increases in plasma renin activity and shows a trend towards blunting of serum aldosterone in the setting of angiotensin II receptor blocker (ARB) use.

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Determinants of intrarenal RAS activation in type 2 diabetes

American Journal of Hypertension ◽

10.1016/s0895-7061(00)01150-x ◽

2000 ◽

Vol 13 (6) ◽

pp. S175-S176 ◽

Cited By ~ 1

Author(s):

D Price

Keyword(s):

Type 2 Diabetes ◽

Ras Activation ◽

Intrarenal Ras

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The Effect of Renal Dysfunction on Circulating Sclerostin Level in Patients with Type 2 Diabetes

Zagazig University Medical Journal ◽

10.21608/zumj.2020.16472.1477 ◽

2020 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

Mahmoud El sebaie ◽

mohamed arafat ◽

mohamed fawzy ◽

ibrahim salem

Keyword(s):

Type 2 Diabetes ◽

Renal Dysfunction ◽

Sclerostin Level

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Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190828161409 ◽

2019 ◽

Vol 19 (20) ◽

pp. 1818-1849 ◽

Cited By ~ 4

Author(s):

Ban Liu ◽

Yuliang Wang ◽

Yangyang Zhang ◽

Biao Yan

Keyword(s):

Diabetes Mellitus ◽

Heart Failure ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Renal Dysfunction ◽

Sglt2 Inhibitors ◽

Sodium Glucose Cotransporter ◽

Glucose Reabsorption ◽

Renal Glucose Reabsorption

: Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. : The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

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Blockade of Renin Angiotensin System Ameliorates the Cardiac Arrhythmias and Sympathetic Neural Remodeling in Hearts of Type 2 DM Rat Model

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190809150921 ◽

2020 ◽

Vol 20 (3) ◽

pp. 464-478 ◽

Cited By ~ 3

Author(s):

Yomna M. Yehya ◽

Abdelaziz M. Hussein ◽

Khaled Ezam ◽

Elsayed A. Eid ◽

Eman M. Ibrahim ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiac Arrhythmias ◽

Sympathetic Nerve ◽

Renin Angiotensin System ◽

Diabetic Rats ◽

Angiotensin System ◽

Type 2 Dm ◽

Type 2 Diabetic ◽

Diabetes Induction

Objectives:: The present study was designed to investigate the effects of renin angiotensin system (RAS) blockade on cardiac arrhythmias and sympathetic nerve remodelling in heart tissues of type 2 diabetic rats. Methods:: Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group: normal rats, b) DM group; after type 2 diabetes induction, rats received 2ml oral saline daily for 4 weeks, c) DM+ ACEi: after type 2 diabetes induction, rats were treated with enalapril (10 mg/kg, orally for 4 weeks) and d) DM+ ARBs: after type 2 diabetes induction, rats were treated with losartan (30 mg/kg, orally for 4 weeks). Results:: In type 2 diabetic rats, the results demonstrated significant prolongation in Q-T interval and elevation of blood sugar, HOMA-IR index, TC, TGs, LDL, serum CK-MB, myocardial damage, myocardial MDA, myocardial norepinephrine and tyrosine hydroxylase (TH) density with significant reduction in serum HDL, serum insulin and myocardial GSH and CAT. On the other hand, blockade of RAS at the level of either ACE by enalapril or angiotensin (Ag) receptors by losartan resulted in significant improvement in ECG parameters (Q-T), cardiac enzymes (CK-MB), cardiac morphology, myocardial oxidative stress (low MDA, high CAT and GSH) and myocardial TH density. Conclusions:: RAS plays a role in the cardiac sympathetic nerve sprouting and cardiac arrhythmias induced by type 2 DM and its blockade might have a cardioprotective effect via attenuation of sympathetic nerve fibres remodelling, myocardial norepinephrine contents and oxidative stress.

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