MECHANISMS IN ENDOCRINOLOGY: Metabolic and inflammatory pathways on the pathogenesis of type 2 diabetes

Abstract

Obesity is the main risk factor for type 2 diabetes (T2D). Studies performed over the last 20 years have identified inflammation as the most important link between these two diseases. During the development of obesity, there is activation of subclinical inflammatory activity in tissues involved in metabolism and energy homeostasis. Intracellular serine/threonine kinases activated in response to inflammatory factors can catalyse the inhibitory phosphorylation of key proteins of the insulin-signalling pathway, leading to insulin resistance. Moreover, during the progression of obesity and insulin resistance, the pancreatic islets are also affected by inflammation, contributing to b-cell failure and leading to the onset of T2D. In this review, we will present the main mechanisms involved in the activation of obesity-associated metabolic inflammation and discuss potential therapeutic opportunities that can be developed to treat obesity-associated metabolic diseases.

Elevations of metabolic risk factors 20 years or more before diagnosis of type 2 diabetes: Experience from the AMORIS study

“…Chronic insulin resistance continuously pressures β cells to produce insulin. This may lead to endoplasmic reticulum stress and low‐grade inflammation, with resultant negative effects on β cells. Given a diabetes‐prone genetic background, such effects could underlie a successive demise of β cells.…”

Exogenous Hydrogen Sulfide Ameliorates Diabetes-Associated Cognitive Decline by Regulating the Mitochondria-Mediated Apoptotic Pathway and IL-23/IL-17 Expression in db/db Mice

“…When T2DM, hyperinsulinemia and insulin-resistance occur, chronic inflammation increases and affects disease development and related complications [41]. IL-17, a proinflammatory cytokine, plays a prominent role in neuroinflammation.…”

Very Low-Calorie Diets in Type 2 Diabetes Mellitus: Effects on Inflammation, Clinical and Metabolic Parameters

“…Indeed, studies have shown that obese individuals present an increase in adipose tissue macrophages and other immune cell infiltration [1]. These cells are key drivers of inflammation via overproduction of inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-6, which are strongly associated with the progression of the obese phenotype and metabolic traits of type 2 DM [36,37]. In addition, the abnormal infiltration of immune cells in adipose tissue has deleterious long-term consequences on the biology of this tissue, as adipocytes are major targets of the pro-inflammatory effects of cytokines released by immune cells [38].…”