Icariin Protects Mouse Insulinoma Min6 Cell Function by Activating the PI3K/AKT Pathway

Zhang, Tao; Qiu, Feifei

doi:10.12659/msm.924453

Cited by 9 publications

(5 citation statements)

References 21 publications

(21 reference statements)

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“…Icariin (ICA) is a major constituent of a flavonoid isolated from the plant Herba epimedii. A wide range of pharmacological effects has been attributed to ICA, including: improvement in neuronal insulin resistance Zou et al (2020) and testicular dysfunction (Zhao et al, 2020); protection of hippocampal neurons Liu et al (2019) and nucleus pulposus cells (Hua et al, 2020); potential against Alzheimer's Disease (Angeloni et al, 2019); and notably, as a traditional Chinese medicine, nourishment of the kidney and reinforcement of Yang. Recent research has demonstrated that ICA treatment reduces blood glucose levels in type 2 diabetic rats and protects pancreatic function Han et al (2015), Li et al (2020), Zhang and Qiu (2020), suggesting that ICA has an anti-T2DM effect. However, the exact mechanism of ICA on T2DN is yet unknown.…”

Section: Introductionmentioning

confidence: 99%

Icariin Ameliorates Diabetic Renal Tubulointerstitial Fibrosis by Restoring Autophagy via Regulation of the miR-192-5p/GLP-1R Pathway

et al. 2021

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Tubulointerstitial fibrosis is one of the most common pathological features of diabetic nephropathy. Autophagy, an intracellular mechanism to remove damaged or dysfunctional cell parts and maintain metabolic homeostasis, is inhibited in diabetic neuropathy. Icariin is a traditional Chinese medicine extract known for nourishing the kidney and reinforcing Yang. In this study, we investigated the effects and mechanism of Icariin on renal function, autophagy, and fibrosis in type 2 diabetic nephropathic rats and in high-glucose-incubated human renal tubular epithelial cells and rat renal fibroblasts (in vitro). Icariin improved diabetes, renal function, restored autophagy, and alleviated fibrosis in type 2 diabetic neuropathic rats and in vitro. After we applied autophagy-related gene 5-small interfering RNA, we found that fibrosis improvement by Icariin was related to autophagy restoration. By detecting serum sex hormone levels, and using dihydrotestosterone, siRNA for androgen receptor, and the androgen receptor antagonist Apalutamide (ARN-509), we found that Icariin had an androgen-like effect and restored autophagy and reduced fibrosis by regulating the androgen receptor. In addition, miR-192-5p levels were increased under high glucose but reduced after dihydrotestosterone and Icariin treatment. Furthermore, dihydrotestosterone and Icariin inhibited miR-192-5p overexpression-induced fibrosis production and autophagy limitation. Glucagon-like peptide-1 receptor (GLP-1R) was downregulated by high glucose and overexpression of miR-192-5p and could be restored by dihydrotestosterone and Icariin. By using ARN-509, we found that Icariin increased GLP-1R expression by regulating the androgen receptor. GLP-1R-siRNA transfection weakened the effects of Icariin on autophagy and fibrosis. These findings indicate that Icariin alleviates tubulointerstitial fibrosis by restoring autophagy through the miR-192-5p/GLP-1R pathway and is a novel therapeutic option for diabetic fibrosis.

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Section: Introductionmentioning

confidence: 99%

Icariin Ameliorates Diabetic Renal Tubulointerstitial Fibrosis by Restoring Autophagy via Regulation of the miR-192-5p/GLP-1R Pathway

et al. 2021

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“… ↓β-cell apoptosis. Li et al (2020) ( Zhang and Qiu, 2020 ) ( Zhong et al, 2018 ) 13 Isorhamnetin ↑Nrf2 ↑HO-1 ↓ CHOP ↓ GRP78 ↑PKCε ↓XBP-1, ↓ATF6, ↓CHOP ↓ Oxidative stress ↓ ER stress ↑ Islet cell survival ↑ Insulin secretion in pancreatic islets Yang et al (2014) ( Li et al, 2023 ; Zheng et al, 2019 ) Kvezereli et al (2008) Rodríguez-Rodríguez et al (2015) 14 Kaempferol ↑ AMPK, ↓ mTOR ↑ AMPK, ↓ mTOR ↓ CHOP ↓ GRP78, ↑ Nrf2 ↑ Autophagy to sustain pancreatic β-cell mass and function. ↑ Autophagy to improve ER stress and lipid mobilization in pancreatic β-cells.…”

Section: Molecular Mechanisms Of Flavonoids In Pancreatic Beta Cell D...mentioning

confidence: 99%

“…Icariin activates phosphorylated AMPK (p-AMPK), leading to the abrogation of the loss of pancreatic islet cells and alleviation of the severity of diabetes in rats ( Li et al, 2020 ), suggesting its beneficial role in improving glucose-stimulated insulin secretion (GSIS), proliferation, and survival of pancreatic β-cells. Icariin has been shown to improve insulin secretion and reduce β-cell apoptosis in uric acid-induced pancreatic β-cell injury by activating PI3K/Akt, suggesting its role in alleviating metabolic dysfunction associated with T2DM ( Zhang and Qiu, 2020 ). Icariin inhibits NF-κΒ's nuclear translocation and the expression of pro-inflammatory cytokines, leading to the blockade of immune cells activation and abrogation of cytokine-induced β-cell apoptosis ( Zhong et al, 2018 ), suggesting a potential therapeutic role in the management of T1DM-related ER stress.…”

Section: Molecular Mechanisms Of Flavonoids In Pancreatic Beta Cell D...mentioning

confidence: 99%

Endoplasmic reticulum stress in pancreatic β-cell dysfunction: The potential therapeutic role of dietary flavonoids

Mbara,

Fotsing,

Ndinteh

et al. 2024

Current Research in Pharmacology and Drug Discovery

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“…For example, activation of phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT) protects β‐cell function and development of insulin resistance. [ 13 ] It remains unclear whether goat milk can promote pancreatic activation of PI3K/AKT pathway and enhance β cell function.…”

Section: Introductionmentioning

confidence: 99%

Goat Milk Improves Glucose Metabolism in Type 2 Diabetic Mice and Protects Pancreatic β‐Cell Functions

Chen,

Zhang,

Niu

et al. 2023

Molecular Nutrition Food Res

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ScopeConsuming goat milk is known to benefit high‐fat diet‐fed and streptozocin (STZ)‐induced diabetic rats, but the underlying mechanisms are unknown. This study is conducted to investigate the metabolic effects of a goat milk diet (a form of goat milk powder) on glucose homeostasis and pancreatic conditions in a mouse model of Type 2 diabetes mellitus (T2DM) induced by STZ.Methods and resultsT2DM mice are fed with a goat‐milk‐based diet containing 10.3% w/w goat milk powder for 10 weeks for investigating the in vivo effects; a β‐cell line MIN6 cells are used to test the in vitro effects of digested goat milk (DGM). Goat milk diet improves the deleterious effects of STZ on fasting glucose levels and glucose tolerance, accelerates pancreatic structure recovery, and alters blood metabolites in mice. Based on the significant differences observed in metabolites, the key pathways, metabolite regulatory enzymes, metabolite molecular modules, and biochemical reactions are identified as critical integrated pathways. DGM promotes the cell activity, glucose transportation, and AKT activation in cultured STZ‐treated MIN6 cells in vitro.ConclusionsGoat milk diet improves glucose homeostasis and pancreatic conditions of T2DM mice, in association with improved blood metabolite profiles and activation of pancreatic AKT pathway.

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Icariin Protects Mouse Insulinoma Min6 Cell Function by Activating the PI3K/AKT Pathway

Cited by 9 publications

References 21 publications

Icariin Ameliorates Diabetic Renal Tubulointerstitial Fibrosis by Restoring Autophagy via Regulation of the miR-192-5p/GLP-1R Pathway

Icariin Ameliorates Diabetic Renal Tubulointerstitial Fibrosis by Restoring Autophagy via Regulation of the miR-192-5p/GLP-1R Pathway

Endoplasmic reticulum stress in pancreatic β-cell dysfunction: The potential therapeutic role of dietary flavonoids

Goat Milk Improves Glucose Metabolism in Type 2 Diabetic Mice and Protects Pancreatic β‐Cell Functions

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