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World J Diabetes. May 15, 2015; 6(4): 598-612
Published online May 15, 2015. doi: 10.4239/wjd.v6.i4.598
Type 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition
Iqra Hameed, Shariq R Masoodi, Shahnaz A Mir, Mudasar Nabi, Khalid Ghazanfar, Bashir A Ganai
Iqra Hameed, Mudasar Nabi, Khalid Ghazanfar, Department of Biochemistry, University of Kashmir, Srinagar 190006, India
Shariq R Masoodi, Shahnaz A Mir, Department of Endocrinology, Sher-I-Kashmir Institute of medical Sciences, Srinagar 190006, India
Shariq R Masoodi, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, United States
Bashir A Ganai, Centre for Research and Development, University of Kashmir, Hazratbal, Srinagar 190006, India
Author contributions: Hameed I drafted the manuscript; Masoodi SR and Ganai BA conceived and designed the manuscript; Mir SA, Nabi M and Ghazanfar K acquired data, formatted figures/table and revised the manuscript.
Supported by Department of Science and Technology, Government of India to Iqra Hameed, No. Wos-A LS 509/2012.
Conflict-of-interest: All the authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Bashir A Ganai, Professor, Director, Centre for Research and Development, University of Kashmir, Hazratbal Rd, Hazratbal, Srinagar 190006, India. bbcganai@gmail.com
Telephone: +91-979-7247851 Fax: +91-194-2415357
Received: August 29, 2014
Peer-review started: August 30, 2014
First decision: September 30, 2014
Revised: October 14, 2014
Accepted: December 29, 2014
Article in press: December 31, 2014
Published online: May 15, 2015
Abstract

Diabetes mellitus is increasing at an alarming rate and has become a global challenge. Insulin resistance in target tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features of type 2 diabetes (T2D). Chronic low-grade inflammation in T2D has given an impetus to the field of immuno-metabolism linking inflammation to insulin resistance and β-cell dysfunction. Many factors advocate a causal link between metabolic stress and inflammation. Numerous cellular factors trigger inflammatory signalling cascades, and as a result T2D is at the moment considered an inflammatory disorder triggered by disordered metabolism. Cellular mechanisms like activation of Toll-like receptors, Endoplasmic Reticulum stress, and inflammasome activation are related to the nutrient excess linking pathogenesis and progression of T2D with inflammation. This paper aims to systematically review the metabolic profile and role of various inflammatory pathways in T2D by capturing relevant evidence from various sources. The perspectives include suggestions for the development of therapies involving the shift from metabolic stress to homeostasis that would favour insulin sensitivity and survival of pancreatic β-cells in T2D.

Keywords: Diabetes mellitus, Inflammation, Insulin resistance, β-cell dysfunction, Adipose tissue

Core tip: Immuno-metabolism, the confluence of metabolism and immune system has emerged as a chief breakthrough especially in the field of diabetes mellitus; a metabolic disorder of great magnitude. Activation of immune system by metabolic stress has opened new insights in the pathogenesis and progression of type 2 diabetes (T2D). The link between metabolic overload and activation of the immune system form the core tip of this review. Metabolic stress can cause pathologic activation of the immune system, thus metabolic disorders like T2D manifest and progress as an inflammatory disorder with severe consequences thereof.