Glucose-Insulin-Potassium Alleviates Intestinal Mucosal Barrier Injuries Involving Decreased Expression of Uncoupling Protein 2 and NLR Family-Pyrin Domain-Containing 3 Inflammasome in Polymicrobial Sepsis

Zhang, Junliang; Chen, Yi‐Ting; Chen, Guangdao; Wang, Tao; Zhang, Juxin; Zeng, Quan

doi:10.1155/2017/4702067

Cited by 4 publications

(3 citation statements)

References 39 publications

(46 reference statements)

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“…UCP2 and UCP3 do not play a role in basal proton leak, but various stimuli can induce their activity, including sepsis. An increase in proton leak and mitochondrial uncoupling proteins have been reported during sepsis in several tissues, in both animal models [85,[196][197][198][199][200] and patients [85,199], however literature specific to the heart is sparse.…”

Section: Proton Leak and Uncouplingmentioning

confidence: 99%

The role of mitochondria in sepsis-induced cardiomyopathy

Stanzani

Duchen

Singer

2019

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

120

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Section: Proton Leak and Uncouplingmentioning

confidence: 99%

The role of mitochondria in sepsis-induced cardiomyopathy

Stanzani

Duchen

Singer

2019

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

120

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“…The intestinal tissue and lung tissue samples were xed with 2.5% pentanediol solution, dehydrated with ethanol, cleared in xylene and embedded in para n.Para n tissue sections were cut at 5-8mm, mounted on slides, stained with HE, and observed for intestinal mucosa and lung tissue damage under light microscopy.We use the CHUI [10] scale to evaluates the intestinal mucosal injury.Mitochondrial autophagic activity was observed under electron microscopy.…”

Section: Histopathological Analysismentioning

confidence: 99%

Effect of Ghrelin on mitophagy in intestinal epithelial cells through the AMPK/FUNDC1 pathway

Tan¹,

Dai²,

Ye³

et al. 2023

Preprint

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Background The incidence and fatality rate of intestinal I/R injury are increasing year by year, which is a problem that the medical community has been concerned about and needs to be solved urgently. The aim of this study is to explore the effect of the gastrointestinal hormone Ghrelin on the AMPK/FUNDC1 mitophagy pathway under intestinal ischemia and reperfusion, and to clarify the mechanism of the protective effect of Ghrelin on intestinal epithelial cells. Method Adult male SD rats were randomized into four groups: sham surgery (Sham), I/R, I/R + Ghrelin, and I/R + Ghrelin + FUNDC1 antagonist group.A model of intestinal ischemia-reperfusion injury was established by clamped the superior mesenteric artery.Rat intestinal epithelium and lung tissues were taken to observe the histopathological morphology and autophagy activity.To measure the IL-6 test for inflammatory factor levels in intestinal epithelial cells, lung lobes, and peripheral blood by ELISA.The expression levels of autophagy proteins including AMPK, pAMPK, FUNDC1, and LC3 in all the rat intestinal epithelial tissues were determined by Western blot.Intracellular ROS levels were measured by a reactive oxygen species fluorescent probe. Using JC-1 probe to detect mitochondrial membrane potential levels.And the expression was determined by quantitative mtDNA by PCR. Result HE staining showed that there was no significant intestinal mucosal damage in Sham group,while intestinal mucosal damage was evident in I/R group.Similarly,the villus structure in the I/R + group was nearly normal but the structural in the I/R + Ghrelin + FUNDC1 antagonist group was like that in I/R group. Compared with the Sham group, IL-6, ROS, and mtDNA levels were significantly increased while the levels of mitochondrial membrane potential and AMPK, FUNDC1, and LC3 protein expression were decreased in group I/R rats (all P <0.05). Compared with the I/R group, the oxidative stress was reduced in the I/R + Ghrelin group, with improved mitochondrial energy metabolism and increased mitophagy protein expression (all P <0.05).However, the I/R+Ghrelin+FUNDC1 inhibitor group reversed the protective effect of the I/R+Ghrelin group, and the results of each test index were close to the I/R group (all P <0.05). Conclusion: Ghrelin can protect against intestinal ischemia and reperfusion injury and distant organs, which may be regulated by the mitophagy pathway of FUNDC1 by AMPK protein.

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“…The mice were randomly allocated into one of four groups (n=7 per group) as follows: PBS control group, LPS exposure group, glucose-potassium (GK) solution plus LPS group (GK/LPS), and glucose-insulin-potassium (GIK) solution plus LPS group (GIK/LPS). To evaluate the insulin effect but avoid hypoglycemia and hypokalemia in vivo, we used the GIK solution, which is consisted of glucose (400 mg/kg), insulin (50 mg/ kg), and potassium chloride (64 mEq/kg) (23), to observe the effect of insulin in vivo. The GK solution, the same components as those of GIK except insulin, was used as vehicle control.…”

Section: Animal Modelmentioning

confidence: 99%

Insulin Reduces Inflammation by Regulating the Activation of the NLRP3 Inflammasome

et al. 2021

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The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is the platform for IL-1β maturation, aimed at mediating a rapid immune response against danger signals which must be tightly regulated. Insulin is well known as the critical hormone in the maintenance of glucose in physiologic response. Previous studies have proved insulin has the anti-inflammatory effect but the molecular mechanism of immunomodulation provided by insulin is not clear so far. Here we investigated whether insulin reduces inflammation by regulating the NLRP3 inflammasome. In the present study, we used LPS and ATP to induce the intracellular formation of the NLRP3 inflammasome. Insulin inhibited the secretion of IL-1β by preventing the assembly of the ASC in THP-1 cells and human CD14+ monocyte-derived macrophages. The phosphorylation status of Syk, p38 mitogen−activated protein kinase (MAPK) and ASC were altered by insulin. These effects were attenuated in THP-1 cells transfected with small interfering RNA targeting insulin receptors. In vivo, administration of glucose–insulin–potassium reduced serum IL-1β level, intestinal ASC speck formation, local macrophage infiltration and alleviated intestinal injury in mice exposed to LPS. Insulin may play an immunomodulatory role in anti-inflammation by regulating the NLRP3 inflammasome.

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Glucose-Insulin-Potassium Alleviates Intestinal Mucosal Barrier Injuries Involving Decreased Expression of Uncoupling Protein 2 and NLR Family-Pyrin Domain-Containing 3 Inflammasome in Polymicrobial Sepsis

Cited by 4 publications

References 39 publications

The role of mitochondria in sepsis-induced cardiomyopathy

The role of mitochondria in sepsis-induced cardiomyopathy

Effect of Ghrelin on mitophagy in intestinal epithelial cells through the AMPK/FUNDC1 pathway

Insulin Reduces Inflammation by Regulating the Activation of the NLRP3 Inflammasome

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