Type 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition

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.

GLP2: an underestimated signal for improving glycaemic control and insulin sensitivity

“…Endotoxemia and low-grade inflammation have been associated with insulin resistance (Hotamisligil 2006, Cani et al 2007, and activation of inflammatory pathways has emerged as an imperative link between T2D and obesity (Hameed et al 2015). It is well accepted that GLP2 is involved in modulation of intestinal permeability (Moran et al 2012).…”

Clinical and metabolic factors associated with chronic low-grade inflammation in type 2 diabetic patients

“…low-grade inflammation; как синонимы используются также термины «микровоспале-ние», «субклиническое воспаление») рассматривается как один из важных механизмов в развитии сахарного диабета 2 типа (СД2) и его сосудистых осложнений [1]. При ожирении в жировой ткани, печени, мышцах уве-личивается количество макрофагов и других клеток им-мунной системы.…”

In Silico Design, Synthesis and In Vitro Evaluation of Quinazolinone Derivatives as Dipeptidyl Peptidase-4 (DPP-IV) Inhibitors

“…Diabetes Mellitus (DM) is defined as a group of metabolic disorders, characterized by high blood glucose levels, significant enough to increase the incidence of microangiopathy (retinopathy, nephropathy and neuropathy) 1,2 . DM is a chronic metabolic disorder that represents a serious public health concern.…”