Insulin resistance in glomerular podocytes: Potential mechanisms of induction

Rogacka, Dorota

doi:10.1016/j.abb.2021.109005

Cited by 20 publications

(14 citation statements)

References 158 publications

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“…FFA content in blood in excess of physiological needs may be the main cause of IR. , An excessive level of FFAs in blood inhibits expression of GLUT-related proteins and a reduced ability of insulin receptors to bind to target cells, resulting ultimately in systemic IR. , It has been proposed that IR develops initially in adipose tissue and then promotes IR development in other organs by secreting several proinflammatory cytokines into the circulation. , This hypothesis was supported by our results showing that ballooning and fibrosis of hepatocytes in DN rats may be attributed to the IR-induced overproduction of proinflammatory cytokines in the liver. Moreover, insulin sensitivity of podocytes can be induced by adipose-tissue IR, which points to a key nexus of adipose-tissue IR and kidney injury in DN that is defective in GLUT4 trafficking-induced glucose dyshomeostasis in podocytes. − Nephrin is required for the maintenance of podocyte integrity. Nephrin has been suggested to be the principal biomarker related to kidney injury, and can be used to evaluate podocyte injury .…”

Section: Discussionmentioning

confidence: 99%

“Multiomics” Analyses Combined with Systems Pharmacology Reveal the Renoprotection of Mangiferin Monosodium Salt in Rats with Diabetic Nephropathy: Focus on Improvements in Renal Ferroptosis, Renal Inflammation, and Podocyte Insulin Resistance

Zhao

Gao

et al. 2022

J. Agric. Food Chem.

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We explored the protection of mangiferin monosodium salt (MGM) on kidney injury in rats with streptozotocin (STZ)-induced diabetic nephropathy (DN) by “multiomics” analysis combined with systems pharmacology, with a specific focus on ferroptosis, inflammation, and podocyte insulin resistance (IR) signaling events in kidneys. MGM treatment afforded renoprotective effects on rats with STZ-induced DN by alleviating systemic IR-induced renal inflammation and podocyte IR. These mechanisms were correlated mainly with the MGM treatment-induced inhibition of the mitogen-activated protein kinase/nuclear factor-kappa B axis and activation of the phosphorylated insulin receptor substrate 1(Tyr608)/phosphorylated phosphatidylinositol 3-kinase/phosphorylated protein kinase B axis in the kidneys of DN rats. MGM had an ameliorative function in renal ferroptosis in rats with STZ-induced DN by upregulating mevalonate-mediated antioxidant capacities (glutathione peroxidase 4 and ferroptosis suppressor protein 1/coenzyme Q10 axis) and weakening acyl-CoA synthetase long-chain family member 4-mediated proferroptotic generation of lipid drivers in kidneys. MGM may be a promising alternative strategy for the treatment of DN.

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Section: Discussionmentioning

confidence: 99%

“Multiomics” Analyses Combined with Systems Pharmacology Reveal the Renoprotection of Mangiferin Monosodium Salt in Rats with Diabetic Nephropathy: Focus on Improvements in Renal Ferroptosis, Renal Inflammation, and Podocyte Insulin Resistance

Zhao

Gao

et al. 2022

J. Agric. Food Chem.

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“…Again, podocytes are incapable of proliferation; as a result, they are the most sensitive part of the glomerular filtration system. High glucose levels, increased free fatty acid echelons, free radicals, transforming growth factor-β, and angiotensin II, as well as hemodynamic influences such as structural stress caused by changes in capillary tension, all can cause podocyte damage [ 16 ].…”

Section: Reviewmentioning

confidence: 99%

Insulin Resistance and Type 2 Diabetes Mellitus: An Ultimatum to Renal Physiology

Sinha¹,

Haque²

2022

Cureus

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Insulin resistance (IR) is stated as diminished insulin action regardless of hyperinsulinemia. The usual target organs for insulin activities are the liver, skeletal muscle, and adipose tissue. Hence, the vasculature and kidneys are nonconventional target organs as the impacts of insulin on these are comparatively separate from other conventional target organs. Vasodilation is achieved by raising endothelial nitric oxide (NO) generation by initiating the phosphoinositide 3-kinase (PI3K) pathway. In insulin-nonresponsive conditions, this process is defective, and there is increased production of endothelin-1 through the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, which predominates the NO effects, causing vasoconstriction. Renal tubular cells and podocytes have insulin receptors, and their purposeful importance has been studied, which discloses critical acts of insulin signaling in podocyte survivability and tubular action. Diabetic nephropathy (DN) is a prevalent problem in individuals with hypertension, poor glycemic management, hereditary susceptibility, or glomerular hyperfiltration. DN could be a significant contributing factor to end-stage renal disease (ESRD) that results from chronic kidney disease (CKD). IR and diabetes mellitus (DM) are the constituents of syndrome X and are accompanied by CKD progression. IR performs a key part in syndrome X leading to CKD. However, it is indistinct whether IR individually participates in enhancing the threat to CKD advancement rather than CKD complexity. CKD is an extensive public health problem affecting millions of individuals worldwide. The tremendous spread of kidney disease intensifies people’s health impacts related to communicable and noncommunicable diseases. Chronic disease regulator policies do not include CKD at global, local, and/or general levels. Improved knowledge of the character of CKD-associated problems might aid in reforming diagnosis, prevention, and management.

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“…Te exclusion criteria are as follows: (1) non-RCT; (2) no control group; (3) the experimental group adopt with other therapeutic methods, except for ZWD + CWM treatment or ZWD alone; (4) the control group was not treated with CWM; (5) nondiabetic nephropathy; (6) they did not meet the DN diagnostic criteria or did not clearly describe the diagnostic criteria; (7) the subjects sufered from severe primary diseases; (8) duplicated detection or published literature; (9) no target outcomes; (10) missing data and unable to contact the investigator.…”

Section: Exclusion Criteriamentioning

confidence: 99%

“…Te predominant pathological characteristics of DN consist of glomerular sclerosis, tubulointerstitial fbrosis, and renal angiopathy. Its pathogenic factors and pathogenesis are complex and are principally related to glycolipid metabolism disorders, insulin resistance, hemodynamic fuctuations, oxidative stress, infammation, endoplasmic reticulum stress, autophagy, exosomes, and intestinal fora; however, the specifc mechanism remains to be further clarifed [6][7][8][9][10]. Clinically, proteinuria, renal function, and diabetes history are considered the main diagnostic indicators of DN.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Zhenwu Decoction in the Treatment of Diabetic Nephropathy: A Systematic Review and Meta-Analysis

Zhou

Liu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. To perform a systematic evaluation of the clinical efficacy and safety of Zhenwu decoction (ZWD) for the treatment of diabetic nephropathy (DN). Methods. PubMed, the China National Knowledge Infrastructure (CNKI), the China Science and Technology Journal Database (VIP), the Chinese Biomedical Literature Database (CBM), and the WanFang databases were searched, and a systematic review and meta-analysis of randomized controlled trials (RCTs) were subsequently conducted to compare the efficacy and safety of ZWD combined with conventional Western medicine (CWM) to conventional therapy alone in the treatment of DN. The Cochrane Handbook for Systematic Reviews of Interventions and GRADE criteria were utilized to assess the quality of the included literature, and RevMan 5.3 software was used for statistical analysis. Results. 13 randomized controlled trials were included, involving 1347 patients with diabetic nephropathy assigned into two subgroups according to the disease duration. The results revealed that compared with conventional therapy alone, ZWD combined with CWM treatment significantly improved the total effective rate (OR = 3.88, 95% CI = (2.87, 5.26), P < 0.00001). Furthermore, ZWD combination therapy also decreased fasting blood glucose (MD = −0.72, 95% CI = (−0.97, −0.48), P < 0.00001), BUN (MD = −1.92, 95% CI = (−3.19, −0.64), P = 0.003), 24-hour urine protein (MD = −0.48, 95% CI = (−0.57, −0.39), P < 0.00001), and serum creatinine levels (MD = −51.17, 95% CI = (−66.95, −35.39), P < 0.00001). However,there was no statistical significance in the effect of combination therapy on creatinine clearance (MD = −0.64, 95% CI = [−8.21,6.92], P = 0.87). However, there was no statistical significance in the effect of combination therapy oncreatinine clearance (MD =−0.64, 95% CI=[−8.21,6.92], P=0.87). Conclusion. ZWD combined with CWM outperformed conventional Western medicine in DN treatment. However, further investigations via multicenter RCTs with rigorous designs and higher quality are still warranted.

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Insulin resistance in glomerular podocytes: Potential mechanisms of induction

Cited by 20 publications

References 158 publications

“Multiomics” Analyses Combined with Systems Pharmacology Reveal the Renoprotection of Mangiferin Monosodium Salt in Rats with Diabetic Nephropathy: Focus on Improvements in Renal Ferroptosis, Renal Inflammation, and Podocyte Insulin Resistance

“Multiomics” Analyses Combined with Systems Pharmacology Reveal the Renoprotection of Mangiferin Monosodium Salt in Rats with Diabetic Nephropathy: Focus on Improvements in Renal Ferroptosis, Renal Inflammation, and Podocyte Insulin Resistance

Insulin Resistance and Type 2 Diabetes Mellitus: An Ultimatum to Renal Physiology

Efficacy and Safety of Zhenwu Decoction in the Treatment of Diabetic Nephropathy: A Systematic Review and Meta-Analysis

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