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The antagonist of CXCR1 and CXCR2 protects db /db mice from metabolic diseases through modulating inflammation.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2019 Dec 01; Vol. 317 (6), pp. E1205-E1217. Date of Electronic Publication: 2019 Oct 01. - Publication Year :
- 2019
-
Abstract
- Interleukin-8 (IL-8, also named CXCL8) binds to its receptors (CXCR1 and CXCR2) with subsequent recruitment of neutrophils and enhancement of their infiltration into inflamed sites, which exaggerates inflammation in many diseases. Recent studies have proposed that metabolic disorders can be attenuated by counteracting certain inflammatory signal pathways. In this study, we examined whether intervention with G31P, an antagonist of CXCL8, could attenuate tissue inflammation and development of metabolic disorders in db/db mice. The db/m and db/db mice were subcutaneously injected with G31P or equivalent normal saline once a day for 6 wk. The physical and metabolic parameters, glucose tolerance, insulin sensitivity, hepatic lipid accumulation, and inflammation markers were measured. G31P improved hepatic insulin sensitivity by modulating expression of genes related to gluconeogenesis and phosphorylated Akt levels. The expressions of several genes encoding proteins involved in de novo lipogenesis were decreased in G31P-treated db/db mice. Meanwhile, immune cell infiltration and cytokine release were attenuated in db/db mice with G31P treatment. G31P also improved the ratio of proinflammatory M1 and anti-inflammatory M2 macrophages. Furthermore, G31P ameliorates metabolic disturbances via inhibition of CXCR1 and CXCR2 pathways in db/db mice. These data suggest that the selective inhibition of CXC chemokines may have therapeutic effects on symptoms associated with obesity and diabetes.
- Subjects :
- Animals
Cytokines drug effects
Cytokines metabolism
Diabetes Mellitus, Type 2 genetics
Disease Models, Animal
Fatty Acids, Nonesterified metabolism
Gluconeogenesis drug effects
Gluconeogenesis genetics
Insulin metabolism
Interleukin-6 metabolism
Interleukin-8 genetics
Interleukin-8 metabolism
Liver metabolism
Liver pathology
Macrophages drug effects
Mice
Phosphorylation
Proto-Oncogene Proteins c-akt drug effects
Proto-Oncogene Proteins c-akt metabolism
Receptors, Interleukin-8A genetics
Receptors, Interleukin-8A metabolism
Receptors, Interleukin-8B genetics
Receptors, Interleukin-8B metabolism
Tumor Necrosis Factor-alpha drug effects
Tumor Necrosis Factor-alpha metabolism
Diabetes Mellitus, Type 2 metabolism
Insulin Resistance
Interleukin-8 antagonists & inhibitors
Lipid Metabolism drug effects
Liver drug effects
Peptide Fragments pharmacology
Receptors, Interleukin-8A antagonists & inhibitors
Receptors, Interleukin-8B antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1555
- Volume :
- 317
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 31573846
- Full Text :
- https://doi.org/10.1152/ajpendo.00117.2019