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Biochem Biophys Res Commun. 2017 May 20;487(1):54-61. doi: 10.1016/j.bbrc.2017.04.012. Epub 2017 Apr 5.

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.

Author information

1
Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India.
2
Department of Biochemistry, Islamia College of Science and Commerce, Srinagar, Jammu & Kashmir 190002, India.
3
International Biomedicine and Genome Center, Balcova, Izmir 35340, Turkey.
4
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
5
Department of Botany, Aligarh Muslim University, Aligarh, Uttar Pradesh 202002, India.
6
Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India. Electronic address: fkhan@jamiahamdard.ac.in.

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.

KEYWORDS:

Adipose tissue; Inflammation; Macrophages; Metformin; Obesity induced insulin resistance; SHP-1

PMID:
28389241
DOI:
10.1016/j.bbrc.2017.04.012
[Indexed for MEDLINE]

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