Rotenone protects against β-cell apoptosis and attenuates type 1 diabetes mellitus

Wu, Mengqiu; Chen, Weiyi; Zhang, Shengnan; Huang, Songming; Zhang, Aihua; Zhang, Yue

doi:10.1007/s10495-019-01566-4

Cited by 18 publications

(7 citation statements)

References 40 publications

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“…Rotenone is a very potent toxin in the low nanomolar range for several neuronal cell lines, such as SH-SY5Y and PC-12 and for primary mesencephalic dopaminergic neurons [ 38 , 39 ]. In other studies, rotenone was used on β-cells as an inhibitor of mitochondrial activity; however, its toxicity was not analyzed systematically and the IC 50 for viability was not determined [ 40 , 41 ]. Here, we reported for INS-1 β-cells a high toxicity of rotenone after 24 h with an IC 50 = 30 nM, which is very similar to that found for dopaminergic-like cell lines.…”

Section: Discussionmentioning

confidence: 99%

β-Cells Different Vulnerability to the Parkinsonian Neurotoxins Rotenone, 1-Methyl-4-phenylpyridinium (MPP+) and 6-Hydroxydopamine (6-OHDA)

et al. 2021

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Neurotoxins such as rotenone, 1-methyl-4-phenylpyridinium (MPP+) and 6-hydroxydopamine (6-OHDA) are well known for their high toxicity on dopaminergic neurons and are associated with Parkinson’s disease (PD) in murine models and humans. In addition, PD patients often have glucose intolerance and may develop type 2 diabetes (T2D), whereas T2D patients have higher risk of PD compared to general population. Based on these premises, we evaluated the toxicity of these three toxins on pancreatic β-cell lines (INS-1 832/13 and MIN6) and we showed that rotenone is the most potent for reducing β-cells viability and altering mitochondrial structure and bioenergetics in the low nanomolar range, similar to that found in dopaminergic cell lines. MPP+ and 6-OHDA show similar effects but at higher concentration. Importantly, rotenone-induced toxicity was counteracted by α-tocopherol and partially by metformin, which are endowed with strong antioxidative and cytoprotective properties. These data show similarities between dopaminergic neurons and β-cells in terms of vulnerability to toxins and pharmacological agents capable to protect both cell types.

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Section: Discussionmentioning

confidence: 99%

β-Cells Different Vulnerability to the Parkinsonian Neurotoxins Rotenone, 1-Methyl-4-phenylpyridinium (MPP+) and 6-Hydroxydopamine (6-OHDA)

et al. 2021

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“…A decrease in body weight and increase in diet are the main clinical features of T1D. [ 22 ] As the results shown in Figure 1b–1d, the body weight in STZ group was significantly lower than that of the control group, while the T1D rats treated with rLZ‐8 (5 mg/kg) had an significant increase in body weight when compared with the STZ model group (Figure 1b). The food intake and water intake were significantly increased in diabetic rats when compared with the control group and significantly decreased after treatment with rLZ‐8 (Figure 1c–1d).…”

Section: Resultsmentioning

confidence: 99%

Recombinant ling zhi-8 enhances Tregs function to restore glycemic control in streptozocin-induced diabetic rats

Xiao

Fang

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives To explore the effect of recombinant LZ-8 (rLZ-8) on streptozocin (STZ)-induced diabetic rats and further illustrate its underlying mechanism. Methods Rats were intraperitoneally injected with single-dose STZ 50 mg/kg for induction of type 1 diabetes (T1D), and then, the diabetic rats were treated with rLZ-8 for 3 months. The clinical symptoms, fasting blood glucose, insulin, cytokines, histopathology, flow cytometry and immunofluorescence were used to evaluate the therapeutic effect and underlying mechanism of rLZ-8 on alleviating diabetes mellitus (DM). Key findings Treatment with rLZ-8 obviously alleviated the clinical symptoms of T1D and dose-dependently reduced the levels of blood glucose, blood lipid and haemoglobin A1c (HbA1c) in diabetic rat model. Meanwhile, rLZ-8 markedly increased insulin secretion and protected against STZ-induced pancreatic tissue injury. Additionally, rLZ-8 dramatically inhibited the levels of TNF-α and IL-1β, and obviously increased the level of IL-10 in serum and pancreas. Further investigation indicated that rLZ-8 treatment significantly increased the number of regulatory T cells (Tregs) and up-regulated the expression of Foxp3 to restore balance between anti-inflammatory and inflammatory cytokines. Conclusions These data suggest that rLZ-8 can antagonize STZ-induced T1D, and its mechanism may be related to inhibit inflammation and enhance Tregs generation.

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“…Type 1 diabetes mellitus (T1DM) is characterized by the dysfunction and apoptosis of pancreatic β cells [11,12]. It occurs primarily in children and adolescents.…”

Section: Discussionmentioning

confidence: 99%

Peptidome Analysis of Pancreatic Tissue Derived from T1DM Mice: Insights into the Pathogenesis and Clinical Treatments of T1DM

Zhang

Zhou

et al. 2021

BioMed Research International

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Bioactive peptides attract growing concerns for their participation in multiple biological processes. Their roles in the pathogenesis of type 1 diabetes mellitus remain poorly understood. In this study, we used LC-MS/MS technology to compare the peptide profiling between pancreatic tissue of T1DM mice and pancreatic tissue of matched control groups. A total of 106 peptides were differentially expressed in T1DM pancreatic tissue, including 43 upregulated and 63 downregulated peptides. Most of the precursor proteins are insulin. Further bioinformatics analysis (GO and pathway analysis) indicated that the potential functions of these differential peptides were tightly related to regulation of endoplasmic reticulum stress. In conclusion, this study highlights new candidate peptides and provides a new perspective for exploring T1DM pathogenesis and clinical treatments.

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Rotenone protects against β-cell apoptosis and attenuates type 1 diabetes mellitus

Cited by 18 publications

References 40 publications

β-Cells Different Vulnerability to the Parkinsonian Neurotoxins Rotenone, 1-Methyl-4-phenylpyridinium (MPP+) and 6-Hydroxydopamine (6-OHDA)

β-Cells Different Vulnerability to the Parkinsonian Neurotoxins Rotenone, 1-Methyl-4-phenylpyridinium (MPP+) and 6-Hydroxydopamine (6-OHDA)

Recombinant ling zhi-8 enhances Tregs function to restore glycemic control in streptozocin-induced diabetic rats

Peptidome Analysis of Pancreatic Tissue Derived from T1DM Mice: Insights into the Pathogenesis and Clinical Treatments of T1DM

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