Type 2 diabetes – An autoinflammatory disease driven by metabolic stress

Abstract

Type 2 diabetes has traditionally been viewed as a metabolic disorder characterised by chronic high glucose levels, insulin resistance, and declining insulin secretion from the pancreas. Modern lifestyle, with abundant nutrient supply and reduced physical activity, has resulted in dramatic increases in the rates of obesity-associated disease conditions, including diabetes. The associated excess of nutrients induces a state of systemic low-grade chronic inflammation that results from production and secretion of inflammatory mediators from the expanded pool of activated adipocytes. Here, we review the mechanisms by which obesity induces adipose tissue dysregulation, detailing the roles of adipose tissue secreted factors and their action upon other cells and tissues central to glucose homeostasis and type 2 diabetes. Furthermore, given the emerging importance of adipokines, cytokines and chemokines in disease progression, we suggest that type 2 diabetes should now be viewed as an autoinflammatory disease, albeit one that is driven by metabolic dysregulation.

Altered mitochondrial metabolism in the insulin‐resistant heart

“…The latter contributes to a local pro‐inflammatory environment of adjacent cardiomyocytes with a substantial increase in macrophage infiltration . The development of inflammation in T2DM has been extensively reviewed, and here we focus on the key concepts of how a low‐grade systemic inflammation in T2DM affects mitochondrial metabolism.…”

Secreted frizzled‐related protein 4 and its implication in obesity and type‐2 diabetes

“…Increased blood glucose levels after food intake trigger pancreatic β‐cells in islets of Langerhans to secrete insulin, which stimulates glucose uptake by skeletal muscles and adipose tissues . Chronic low‐grade inflammation of islets in response to metabolic stress leads toward T2D . Abnormal increased levels of proinflammatory cytokines including Creactive protein (CRP), interleukin 6 (IL‐6), and IL‐1β are also observed in T2D patients that might activate innate immune response resulting in inflammatory mechanisms in pancreatic islets .…”

“…Abnormal increased levels of proinflammatory cytokines including Creactive protein (CRP), interleukin 6 (IL‐6), and IL‐1β are also observed in T2D patients that might activate innate immune response resulting in inflammatory mechanisms in pancreatic islets . Furthermore, different proinflammatory mediators including IL‐6, Tumornecrosis factor‐α (TNF‐α), IL‐1β, and IL‐1 dependent cytokines are released in islets of pancreas in response to hyperglycemia …”

“…White adipose tissues (WATs) of humans secrete about 300 adipokines and most of them exhibit alterations in expression during obesity and causes low‐grade chronic inflammation and altered insulin sensitivity . The Wnt proteins are involved in cellular functions and differentiation in various tissues including WATs.…”

Wingless-type MMTV integration site family member 5a: a novel biomarker regulated in type 2 diabetes mellitus and diabetic kidney disease

“…Multiple factors have been proposed to cause pathological changes in diabetes mellitus and its renal complications. Previous studies have shown that low-grade chronic inflammation and activation of the renin-angiotensin system (RAS) all accelerate the development of diabetes and its renal complications [4,5]. However, it is disappointing that the exact pathogenesis leading to T2DM and DKD remain not fully elucidated.…”