Chronic intermittent hypoxia disturbs insulin secretion and causes pancreatic injury via the MAPK signaling pathway

Wang, Yeying; Han, Bing; Niu, Xiaoqun; Ai, Li; Cao, Yu; Li, Ran; Li, Yongxia

doi:10.1139/bcb-2016-0167

Cited by 31 publications

(29 citation statements)

References 24 publications

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“…The enhanced expression of HIF-1α, NF-κB, and p-P44/42 MAPK was found in the mice treated with CIH. These findings were consistent with previous studies (17,34,(36)(37)(38).…”

Section: R O B U S T E V I D E N C E S H O W E D T H a T O Ssupporting

confidence: 94%

Decreased expression of hepatic cytochrome P450 1A2 (CYP1A2) in a chronic intermittent hypoxia mouse model

et al. 2018

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Background: Hepatic cytochrome P450 (CYP) isoforms, CYP1A2, is one of important enzymes for many drugs metabolism. Studies have confirmed that sustained hypoxia can influence the expression of hepatic CYP, including CYP1A2. The impact of chronic intermittent hypoxia (CIH), a marked characteristic of sleep apnea, on CYP1A2 remains unclear. The aim of the present study was to evaluate the effect of CIH on the expression of hepatic CYP1A2 in a mouse model with sleep apnea.Methods: Twenty four old male (6-8 weeks) C57BL/6J mice (n=12 in each group) were randomly assigned to either normoxia group or CIH group. Mice in CIH group underwent 12 weeks intermittent hypoxia exposure. The different gene expression of hepatic CYP1A2 between two groups was analyzed by quantity real-time polymerase chain reaction. The protein levels of hepatic CYP1A2 in each group were observed by using western blotting and immunohistochemistry.Results: After 12 weeks of exposure to intermittent hypoxia, the expression of hepatic CYP1A2, at the mRNA and protein levels was decreased more significantly in the CIH group than the normoxia group (P<0.01).Conclusions: CIH contributes to inhibiting the expression of hepatic CYP1A2. This implies that the dosage of drugs metabolized by CYP1A2, should be adjusted in patients with sleep apnea.

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“…The enhanced expression of HIF-1α, NF-κB, and p-P44/42 MAPK was found in the mice treated with CIH. These findings were consistent with previous studies (17,34,(36)(37)(38).…”

Section: R O B U S T E V I D E N C E S H O W E D T H a T O Ssupporting

confidence: 94%

Decreased expression of hepatic cytochrome P450 1A2 (CYP1A2) in a chronic intermittent hypoxia mouse model

et al. 2018

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“…As a component of these FFAs, PA has been reported to be involved in the development of apoptosis and the dysfunction of islet β-cells. Increasing oxidative stress and ERS are also known to be involved in this process [ 44 , 45 ], particularly in the MAPK-dependent apoptosis and dysfunction of islet cells [ 46 ]. As a member of the MKP family, MKP-5 is closely associated with insulin resistance and inflammation [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

MKP-5 Relieves Lipotoxicity-Induced Islet β-Cell Dysfunction and Apoptosis via Regulation of Autophagy

Zhao

et al. 2020

IJMS

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Mitogen-activated protein kinase phosphatase-5 (MKP-5) is a regulator of extracellular signaling that is known to regulate lipid metabolism. In this study, we found that obesity caused by a high-fat diet (HFD) decreased the expression of MKP-5 in the pancreas and primary islet cells derived from mice. Then, we further investigated the role of MKP-5 in the protection of islet cells from lipotoxicity by modulating MKP-5 expression. As a critical inducer of lipotoxicity, palmitic acid (PA) was used to treat islet β-cells. We found that MKP-5 overexpression restored PA-mediated autophagy inhibition in Rin-m5f cells and protected these cells from PA-induced apoptosis and dysfunction. Consistently, a lack of MKP-5 aggravated the adverse effects of lipotoxicity. Islet cells from HFD-fed mice were infected using recombinant adenovirus expressing MKP-5 (Ad-MKP-5), and we found that Ad-MKP-5 was able to alleviate HFD-induced apoptotic protein activation and relieve the HFD-mediated inhibition of functional proteins. Notably, HFD-mediated impairments in autophagic flux were restored by Ad-MKP-5 transduction. Furthermore, the autophagy inhibitor 3-methyladenine (3-MA) was used to treat Rin-m5f cells, confirming that the MKP-5 overexpression suppressed apoptosis, dysfunction, inflammatory response, and oxidative stress induced by PA via improving autophagic signaling. Lastly, employing c-Jun amino-terminal kinas (JNK), P38, or extracellular-regulated kinase (ERK) inhibitors, we established that the JNK and P38 MAPK pathways were involved in the MKP-5-mediated apoptosis, dysfunction, and autophagic inhibition observed in islet β cells in response to lipotoxicity.

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“…All MAPK pathways include central three-tiered "core signaling modules" as MAPKkinase-kinase, in which MAPKs are activated by associated Tyr and Thr phosphorylation (Kyriakis and Avruch, 2001). They are differentially involved in the regulation of inflammatory cytokines in the hypoxic/ischemic conditions (Tan et al, 2013;Wang et al, 2017;Wu et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

The δ-Opioid Receptor Differentially Regulates MAPKs and Anti-inflammatory Cytokines in Rat Kidney Epithelial Cells Under Hypoxia

Luo

Song

et al. 2020

Front. Physiol.

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Hypoxic injury is one of the most important factors in progressive kidney disorders. Since we have found that δ-opioid receptor (DOR) is neuroprotective against hypoxic stress through a differential regulation of mitogen-activated protein kinases (MAPKs) and anti-inflammatory cytokines, we asked if DOR that is highly expressed in the kidney can modulate renal MAPKs and anti-inflammatory cytokines under hypoxia. We exposed cultured rat kidney epithelial cells (NRK-52E) to prolonged hypoxia (1% O 2) with applications of specific DOR agonist or/and antagonist to examine if DOR affects hypoxia-induced changes in MAPKs and anti-inflammatory cytokines. The results showed that endogenous DOR expression remained unchanged under hypoxia, while DOR activation with UFP-512 (a specific DOR agonist) reversed the hypoxia-induced up-regulation of ERK1/2 and p38 phosphorylation. DOR inhibition with naltrindole had no appreciable effect on the hypoxia-induced changes in ERK1/2 phosphorylation, but increased p38 phosphorylation. DOR inhibition with naltrindole attenuated the effects of DOR activation on the changes in ERK1/2 and p38 phosphorylation in hypoxia. Moreover, DOR activation/inhibition differentially affected the expression of transcriptional repressor B-cell lymphoma 6 (Bcl-6), anti-inflammatory cytokines tristetraprolin (TTP), and interleukin-10 (IL-10). Taken together, our novel data suggest that DOR activation differentially regulates ERK1/2, p38, Bcl-6, TTP, and IL-10 in the renal cells under hypoxia.

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Chronic intermittent hypoxia disturbs insulin secretion and causes pancreatic injury via the MAPK signaling pathway

Cited by 31 publications

References 24 publications

Decreased expression of hepatic cytochrome P450 1A2 (CYP1A2) in a chronic intermittent hypoxia mouse model

Decreased expression of hepatic cytochrome P450 1A2 (CYP1A2) in a chronic intermittent hypoxia mouse model

MKP-5 Relieves Lipotoxicity-Induced Islet β-Cell Dysfunction and Apoptosis via Regulation of Autophagy

The δ-Opioid Receptor Differentially Regulates MAPKs and Anti-inflammatory Cytokines in Rat Kidney Epithelial Cells Under Hypoxia

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