title: Inhibition of Src homology 2 domain containing protein tyrosine phosphatase as the possible mechanism of metformin-assisted amelioration of obesity induced insulin resistance in high fat diet fed C57BL/6J mice.
abstract: SHP-1 (Src homology 2 domain containing protein tyrosine phosphatase) is a known negative regulator of insulin signaling and inflammation. To date, the molecular mechanism of metformin in modulating SHP-1 expression has remained elusive. In the present study, we have investigated the role of SHP-1 in relation to anti-hyperglycemic and anti-inflammatory actions of metformin in an obese phenotype mouse model. We observed that metformin treatment significantly reduced SHP-1 activity in obese mice, leading to improved insulin sensitivity. Additionally, metformin down regulated inflammatory markers like TLR2, TLR4, CD80, CD86, NF-κB, STAT1 and suppressed adipose tissue inflammation by efficiently polarizing adipose tissue macrophages toward anti-inflammatory state by way of indirect inhibition of SHP-1 mRNA and protein expressions. Our study suggests that metformin exerts its insulin sensitizing effects via inhibition of SHP-1 activity and expression.
authors.affiliation: Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Yadhu
authors.initials: Y
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry, Islamia College of Science and Commerce, Srinagar, Jammu & Kashmir 190002, India.
authors.forename: Samina
authors.initials: S
authors.lastname: Bashir
authors.affiliation: International Biomedicine and Genome Center, Balcova, Izmir 35340, Turkey.
authors.lastname: Ansarullah
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Mohemmed
authors.initials: M
authors.lastname: Faraz Khan
authors.affiliation: Department of Botany, Aligarh Muslim University, Aligarh, Uttar Pradesh 202002, India.
authors.forename: Altaf
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India. Electronic address: fkhan@jamiahamdard.ac.in.
authors.forename: Farah
authors.initials: F
authors.lastname: Khan
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D008687:Metformin; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse
keywords: Adipose tissue; Inflammation; Macrophages; Metformin; Obesity induced insulin resistance; SHP-1