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

Visniauskas, Bruna; Arita, Danielle Yuri; Rosales, Carla B.; Feroz, Mohammed A; Luffman, Christina; Accavitti, Michael J.; Dawkins, Gabrielle; Hong, Jennifer; Curnow, Andrew C.; Thethi, Tina K.; Lefante, John J.; Jaimes, Edgar A.; Mauvais-Jarvis, Franck; Fonseca, Vivian; Prieto, Minolfa C.

doi:10.1186/s13293-021-00374-3

Cited by 10 publications

(10 citation statements)

References 62 publications

(102 reference statements)

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“…However, exogenous addition of sPRR has been demonstrated to promote adipose tissue beigeing in male mice (33) and improve glucose and insulin balance in morbidly obese male mice (19). In the present study, we found that human sPRR expression in adipose tissue did not affect glucose and insulin metabolism irrespective of circulating sPRR levels, suggesting that plasma human sPRR in males may not play a role in glucose and insulin homeostasis, similar to reported findings in human studies (26). The discrepancies in findings between human and mouse sPRR may be due to specie differences.…”

Section: Discussionsupporting

confidence: 90%

“…This data suggests that the influence of circulating sPRR on glucose and insulin metabolism could be sex and location (local vs circulating) dependent. Clinical studies do not show an association between plasma sPRR and glucose metabolism in men (26). Still studies in male mice show that plasma sPRR could be implicated in glucose and insulin homeostasis.…”

Section: Discussionmentioning

confidence: 92%

“…Clinical studies do not show an association between plasma sPRR and glucose metabolism in men (26). Still studies in male mice show that plasma sPRR could be implicated in glucose and insulin homeostasis.…”

Section: Discussionmentioning

confidence: 96%

“…Clinical studies have shown that plasma sPRR is elevated and associated with hyperglycemia in women but not men with type 2 diabetes (26). Moreover, increased circulating sPRR is associated with gestational diabetes (32).…”

Section: Discussionmentioning

confidence: 99%

“…In humans, obesity is known to elevate circulating sPRR (25) whereas weight loss after bariatric surgery reduced circulating sPRR (25). Additionally, plasma sPRR is elevated in women with type 2 diabetes (26) and in hypertensive patients on RAS blockers suggesting that elevated circulating sPRR in humans is associated with obesity and BP regulation, but little is known about its role in sex-specific protective or detrimental effects on cardiometabolic function during obesity.…”

Section: Introductionmentioning

confidence: 99%

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Human Soluble Prorenin Receptor Expressed in Adipose Tissue Improves Insulin Sensitivity and Endothelial Function in Obese Female Mice

Arthur,

Ahmed,

Nichols

et al. 2024

Preprint

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Increased circulating levels of the soluble prorenin receptor (sPRR), a component of the renin angiotensin system (RAS), plays a role in obesity, glucose, and insulin homeostasis. However, elevated plasma sPRR in diabetic patients has been shown correlated with hyperglycemia in women but not men. Hence, the current study sought to understand the contribution of human sPRR (HsPRR) produced in the adipose tissue (Adi) on adipogenesis, and glucose and insulin balance in obesity settings. Adi-HsPRR mice were generated by breeding human sPRR-Myc-tag transgenic mice with mice expressing Adiponectin/Cre. The mouse model was validated by detecting 28kDa myc-tagged HsPRR by western blotting. Adipose HsPRR expression did not change circulating sPRR in female mice fed a standard chow diet or high fat diet (HFD) but increased plasma sPRR in male Adi-HsPRR mice fed a HFD compared to HFD-fed controls. Yet, Adi-HsPRR improved insulin sensitivity, vascular relaxation and the vasodilator agent Ang 1-7 in obese female mice but not in the male counterparts. Moreover, Adi-HsPRR expression reduced the expression of the adipogenic genes SREBP1C and CD36 only in gonadal white adipose from obese female mice, signifying that adipose tissue-derived HsPRR exerts a sex-specific effect on insulin sensitivity and endothelial function which seems independent of circulating sPRR.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Human Soluble Prorenin Receptor Expressed in Adipose Tissue Improves Insulin Sensitivity and Endothelial Function in Obese Female Mice

Arthur,

Ahmed,

Nichols

et al. 2024

Preprint

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Genetic Ablation of Prorenin Receptor in the Rostral Ventrolateral Medulla Influences Blood Pressure and Hydromineral Balance in Deoxycorticosterone-Salt Hypertension

Mathieu,

Fekete,

Muskus

et al. 2023

Function

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Non-enzymatic activation of renin via its interaction with prorenin receptor (PRR) has been proposed as a key mechanism of local renin-angiotensin system (RAS) activation. The presence of renin and angiotensinogen has been reported in the rostral ventrolateral medulla (RVLM). Overactivation of bulbospinal neurons in the RVLM is linked to hypertension (HTN). Previous studies have shown that the brain RAS plays a role in the pathogenesis of the deoxycorticosterone (DOCA)-salt HTN model. Thus, we hypothesized that PRR in the RVLM is involved in the local activation of the RAS, facilitating the development of DOCA-salt HTN. Selective PRR ablation targeting the RVLM (PRRRVLM-Null mice) resulted in an unexpected sex-dependent and biphasic phenotype in DOCA-salt HTN. That is, PRRRVLM-Null females (but not males) exhibited a significant delay in achieving maximal pressor responses during the initial stage of DOCA-salt HTN. Female PRRRVLM-Null subsequently showed exacerbated DOCA-salt-induced pressor responses during the “maintenance” phase with a maximal peak at 13 days on DOCA-salt. This exacerbated response was associated with an increased sympathetic drive to the resistance arterioles and the kidney, exacerbated fluid and sodium intake and output in response to DOCA-salt, and induced mobilization of fluids from the intracellular to extracellular space concomitant with elevated vasopressin. Ablation of PRR suppressed genes involved in RAS activation and catecholamine synthesis in the RVLM but also induced expression of genes involved in inflammatory responses. This study illustrates complex and sex-dependent roles of PRR in the neural control of BP and hydromineral balance through autonomic and neuroendocrine systems.

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Renal-Derived Human sPRR Does Not Increase Blood Pressure in High Fat Diet Mice

Arthur,

Biel,

Osborn

et al. 2024

Preprint

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Obesity is a risk factor for hypertension. Obesity-related hypertension has been associated with elevated plasma soluble prorenin receptor (sPRR) particularly in men. Additionally, renal PRR and sPRR protein expression is upregulated during obesity and diabetes. However, whether renal-derived human sPRR (HsPRR) may influence the intrarenal RAS status to regulate blood pressure and kidney function during obesity has not been investigated. Therefore, we studied the role of collecting duct (CD) derived-HsPRR on blood pressure and kidney function in male and female mice during obesity. Eight-week-old male and female CD-HsPRR mice were placed on a high fat diet for 25 weeks. HsPRR increased renal sPRR concentration but did not change its circulating levels in male and female littermates compared to CTL mice. GFR, water intake and urine flow were not influenced by the CD-HsPRR expression in either sex. Moreover, after 21 weeks of HFD, blood pressure was similar between groups, while only male CD-HsPRR mice showed an impaired pressor response to losartan. In the renal cortex, male CD-HsPRR mice showed increased renin and AT1R mRNA expression associated with increased AQP2, and ENaC subunits protein expression. These data indicate that renal-derived HsPRR induces local upregulation in renin, AT1R and sodium/water transporters in male mice without altering renal hemodynamics or blood pressure. In obese females, CD-HsPRR expression did not affect blood pressure or renal function, which suggests that females may be protected from obesity induced renal function impairment and hypertension.

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

Cited by 10 publications

References 62 publications

Human Soluble Prorenin Receptor Expressed in Adipose Tissue Improves Insulin Sensitivity and Endothelial Function in Obese Female Mice

Human Soluble Prorenin Receptor Expressed in Adipose Tissue Improves Insulin Sensitivity and Endothelial Function in Obese Female Mice

Genetic Ablation of Prorenin Receptor in the Rostral Ventrolateral Medulla Influences Blood Pressure and Hydromineral Balance in Deoxycorticosterone-Salt Hypertension

Renal-Derived Human sPRR Does Not Increase Blood Pressure in High Fat Diet Mice

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