Inflammation and insulin resistance: New targets encourage new thinking

Johnson, Andrew M.; Hou, Shaocong; Li, Pingping

doi:10.1002/bies.201700036

Cited by 20 publications

(6 citation statements)

References 80 publications

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“…Phosphorylation of IRS-1 at Ser307, a potential mechanism underlying insulin resistance, attenuates insulin signaling pathways (19). It has been shown that targeting antiinflammatory cytokines might restore insulin sensitivity (27,28). Furthermore, diabetic drugs with anti-inflammatory properties protect against cardiovascular complications in patients with type 2 diabetes (29).…”

Section: Discussionmentioning

confidence: 99%

A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation

2021

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Systemic inflammation is related to hyperglycemia in diabetes mellitus (DM). C-C chemokine motif ligand (CCL) 4 is upregulated in type 1 & type 2 DM patients. This study aimed to investigate if CCL4 could be a potential target to improve blood sugar control in different experimental DM models. Streptozotocin-induced diabetic mice, Leprdb/JNarl diabetic mice, and C57BL/6 mice fed a high fat diet were used as the type 1 DM, type 2 DM, and metabolic syndrome model individually. Mice were randomly assigned to receive an anti-CCL4 neutralizing monoclonal antibody. The pancreatic β-cells were treated with streptozotocin for in vitro experiments. In streptozotocin-induced diabetic mice, inhibition of CCL4 controlled blood sugar, increased serum insulin levels, increased islet cell proliferation and decreased pancreatic interleukin (IL)-6 expression. In the type 2 diabetes and metabolic syndrome models, CCL4 inhibition retarded the progression of hyperglycemia, reduced serum tumor necrosis factor (TNF)-α and IL-6 levels, and improved insulin resistance via reducing the phosphorylation of insulin receptor substrate-1 in skeletal muscle and liver tissues. CCL4 inhibition directly protected pancreatic β-cells from streptozotocin stimulation. Furthermore, CCL4-induced IL-6 and TNF-α expressions could be abolished by siRNA of CCR2/CCR5. In summary, direct inhibition of CCL4 protected pancreatic islet cells, improved insulin resistance and retarded the progression of hyperglycemia in different experimental models, suggesting the critical role of CCL4-related inflammation in the progression of DM. Future experiments may investigate if CCL4 could be a potential target for blood sugar control in clinical DM.

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Section: Discussionmentioning

confidence: 99%

A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation

2021

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“…There was a significant decrease in M1 macrophage gene expression by BBR, which was significantly increased by LTB4 [ 39 ]. The possible mechanism of BBR could be related to its effect on the LTB4–BLT1 axis, known as a target for treating metabolic diseases [ 40 ]. As a consequence of this interaction, BBR mediated the down-regulation of p-NF-κB expression in macrophages caused by LTB4 [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

A Mechanistic Review on How Berberine Use Combats Diabetes and Related Complications: Molecular, Cellular, and Metabolic Effects

Askari,

Khosravi,

Baradaran Rahimi

et al. 2023

Pharmaceuticals

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Berberine (BBR) is an isoquinoline alkaloid that can be extracted from herbs such as Coptis, Phellodendron, and Berberis. BBR has been widely used as a folk medicine to treat various disorders. It is a multi-target drug with multiple mechanisms. Studies have shown that it has antioxidant and anti-inflammatory properties and can also adjust intestinal microbial flora. This review focused on the promising antidiabetic effects of BBR in several cellular, animal, and clinical studies. Based on previous research, BBR significantly reduced levels of fasting blood glucose, hemoglobin A1C, inflammatory cytokines, and oxidative stress markers. Furthermore, BBR stimulated insulin secretion and improved insulin resistance through different pathways, including up-regulation of protein expression of proliferator-activated receptor (PPAR)-γ, glucose transporter (GLUT) 4, PI3K/AKT, and AMP-activated protein kinase (AMPK) activation. Interestingly, it was demonstrated that BBR has protective effects against diabetes complications, such as diabetic-induced hepatic damage, cardiovascular disorders, nephropathy, and neuropathy. Furthermore, multiple clinical trial studies have emphasized the ameliorative effects of BBR in type 2 diabetic patients.

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“…In addition to classical pro-inflammatory cytokines, Gal-3 is also considered a key factor leading to insulin resistance. Gal-3 expression is up-regulated in CD11c + macrophages isolated from the adipose tissue of insulin resistant obese mice, but not after these mice had been changed to a normal chow diet and become insulin sensitive [11]. The cytokines secreted by the inflamed immune cells may contribute to the improvement of glycolipid metabolism after the depletion of CD11c + cells by the piperine treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Pro-inflammatory cytokine galectin-3 (Gal-3) plays a vital disease-exacerbating role in autoimmune/inflammatory diseases including obesity-associated diabetes [11]. Gal-3, an approximate 31-kDa protein with a specific carbohydrate recognition domain and a conserved N-terminal domain, functions as an inflammatory mediator [12], which is mainly secreted by M 1 -like macrophages in visceral adipose tissues and can directly enhance macrophage chemotaxis.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effect of piperine ameliorates insulin resistance in monosodium glutamate–treated obese mice

Yuan

Zhou

et al. 2020

Preprint

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Background : Metabolic inflammation has been considered as an essential event in obesity-induced diabetes and insulin resistance. In obesity, an increasing number of macrophages recruited into visceral adipose tissues undergo significant M 1 -like polarization, secreting variable amounts of pro-inflammatory cytokines and causing insulin resistance. Piperine has been proven to have excellent anti-inflammatory activity and has therapeutic effects on a variety of inflammatory diseases. Therefore, we investigated the effect of piperine on adipose tissue inflammation and insulin resistance in obese mice. Methods: In this study, the monosodium glutamate (MSG) obese mice model was used. The 6-month-old MSG mice were divided into three groups, which were treated with piperine (40 mg/kg/day), metformin (150 mg/kg/day) and vehicle for successive 10 weeks, respectively. Meanwhile, the 6-month-old normal mice without MSG treatment were selected as normal controls. Results: When the obesity model was successfully established, obesity degree, insulin resistance, fasting blood glucose(FBG) and serum lipid profiles were significantly increased. Our results showed that the 10-week administration of piperine (40 mg/kg/d) not only significantly decreased the elevated FBG, serum TC and TG levels, but also enhanced infusion rate in hyperglycemic clamp experiment and improved the oral glucose intolerance as well as abnormal insulin tolerance in adult MSG obese mice. Additionally, piperine significantly decreased the total and differential white blood cell (WBC) count and the serum level of lipopolysaccharide (LPS), pro-inflammatory cytokines such as galectin-3 (Gal-3), interleukin-1β (IL-1β). Furthermore, piperine clearly down-regulated the mRNA levels of pro-inflammatory cytokines and the protein levels of M 1 -like polarization marker CD11c and Gal-3 in adipose tissues. In addition, the in vitro study showed that piperine inhibited LPS- stimulated polarization of RAW 264.7 cells toward the M 1 phenotype. Conclusions: In summary, these findings demonstrated that piperine could significantly inhibit body weight gain, reduce fat accumulation, rectify glycolipid metabolism disorders, improve severe insulin resistance and ameliorates systemic metabolic inflammation in MSG obesity mice. Our study indicates that piperine, as a potential natural alkaloid, can be used in the treatment of obesity-associated diabetes by delaying the progression of obesity-induced insulin resistance.

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Inflammation and insulin resistance: New targets encourage new thinking

Cited by 20 publications

References 80 publications

A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation

A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation

A Mechanistic Review on How Berberine Use Combats Diabetes and Related Complications: Molecular, Cellular, and Metabolic Effects

Anti-inflammatory effect of piperine ameliorates insulin resistance in monosodium glutamate–treated obese mice

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