Dataset Information

Hyperinsulinemia contributes to impaired-glucose-tolerance-induced renal injury via mir-7977/SIRT3 signaling.

ABSTRACT:

Background

Increasing evidence indicates that impaired glucose tolerance (IGT) is independently associated with chronic kidney disease, but the characteristics and underlying mechanisms remain largely unknown.

Methods

Here, the cross-sectional study was performed to study the characteristics of IGT-induced renal injury (IGT-RI). Furthermore, urine microRNA profile was evaluated and microRNAs involved in tubular injury were determined by in-vitro experiments.

Results

It was found that 12.1% of IGT patients had microalbuminuria, which we termed "IGT-RI." Overall, 100% of patients with IGT-RI exhibited reabsorption dysfunction and 58.3% had structural damage in the renal tubules. Two-hour postprandial insulin, retinol-binding protein, and N-acetyl-β-glucosaminidase were significantly associated with microalbuminuria and they were independent risk factors for IGT-RI. The expression of mir-7977 was altered in IGT-RI patients and may be involved in cellular response to oxidative stress. In proximal tubule epithelial cells in vitro, a high level of insulin increased the expression of mir-7977 and decreased that of sirtuin 3 (SIRT3), leading to oxidative stress. Overexpression of mir-7977 further decreased SIRT3 expression, whereas inhibition of mir-7977 had the opposite effect. Furthermore, mir-7977 can bind to the 3'-untranslated region of SIRT3 mRNA and inhibit its expression. Moreover, inhibition of SIRT3 reduced the expression of cubilin and the endocytosis of albumin.

Conclusions

In conclusion, IGT-RI mainly manifests as tubular injury, especially reabsorption dysfunction. Compensatory hyperinsulinemia may be involved. A high level of insulin can activate mir-7977/SIRT3 signaling, resulting in tubular injury by inducing oxidative stress as well as reabsorption dysfunction by inhibiting the expression of cubilin, ultimately contributing to IGT-RI.

SUBMITTER: Gao Z

PROVIDER: S-EPMC7236569 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Hyperinsulinemia contributes to impaired-glucose-tolerance-induced renal injury <i>via</i> mir-7977/SIRT3 signaling.

Gao Zhongai Z Wang Ziyan Z Zhu Hong H Yuan Xinxin X Sun Mengdi M Wang Jingyu J Zuo Minxia M Cui Xiao X Han Ying Y Zhang Yi Y Yang Shaohua S Qin Yongzhang Y Xu Jie J Yang Juhong J Chang Baocheng B

Therapeutic advances in chronic disease 20200508

<h4>Background</h4>Increasing evidence indicates that impaired glucose tolerance (IGT) is independently associated with chronic kidney disease, but the characteristics and underlying mechanisms remain largely unknown.<h4>Methods</h4>Here, the cross-sectional study was performed to study the characteristics of IGT-induced renal injury (IGT-RI). Furthermore, urine microRNA profile was evaluated and microRNAs involved in tubular injury were determined by <i>in-vitro</i> experiments.<h4>Results</h4> ...[more]

PMID: 32523663

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