Inflammatory mechanisms of diabetic complications

Abstract

Activation of inflammatory processes may contribute to the development of type 2 diabetes mellitus. In addition, inflammation appears to be a major mechanism responsible for vascular damage leading to the clinically well-recognized complications of diabetes. Inflammatory cytokine and chemokine mediators released from visceral fat contribute to atherosclerotic plaque formation and increased risk for myocardial infarction and stroke. Activation of growth factors and adhesion molecules may promote the movement of inflammatory cells into the renal microvasculature, predisposing to the development of diabetic nephropathy. Emerging evidence also indicates that markers of inflammation are associated with the more severe forms of diabetic retinopathy. Future approaches to the treatment of diabetic complications may involve regulation of inflammatory processes, specifically targeting factors that contribute to vascular damage.

Peptide-based inhibition of IκB kinase/nuclear factor-κB pathway protects against diabetes-associated nephropathy and atherosclerosis in a mouse model of type 1 diabetes

“…Moreover, hyperglycaemia upregulates inflammatory gene expression and hastens the recruitment of leucocytes [16,17,21], which further contribute to diabetic renal injury, either by direct interaction with mesangial and tubular cells or by releasing pro-inflammatory and pro-fibrotic mediators [4,5]. Our work demonstrates that NBD peptide administration in diabetic mice improves renal function variables (creatinine and albumin-to-creatinine ratio) and glomerular lesions (leucocyte infiltration, hypertrophy, mesangial expansion and glomerulosclerosis).…”

“…Hyperglycaemia, hyperlipidaemia and chronic inflammation are involved in the clinically well-recognised complications of diabetes. In fact, released inflammatory cytokines and chemokines contribute to atherosclerotic plaque formation, while growth factors and adhesion molecules promote inflammatory cell recruitment into the renal microvasculature, predisposing patients to diabetic nephropathy development [4,5].…”

Anti-Inflammatory Role of MicroRNA-146a in the Pathogenesis of Diabetic Nephropathy

“…10,46,47 Macrophages are among the major inflammatory/ immune cells that infiltrate into the kidneys under diabetic conditions and create a proinflammatory environment. 21 This in turn affects almost all renal cells, contributing to ECM accumulation, fibrosis, cellular dysfunction, and eventually proteinuria.…”

Mechanisms by which diabetes increases cardiovascular disease

“…Different molecular mechanisms associated with hyperglycemia have been identified including 1. increased glucose flux through the polyol pathway [5], 2. formation of advanced glycation end products (AGE) [5], (3) activation of protein kinase C (PKC) [5,6], 4. increased glucose flux through the hexosamine pathway [5], and activation of the 12/15-lipoxygenase (12/15-LO) pathway [7,8]. All these mechanisms finally lead to increased superoxide formation [5] (Figure 1).…”

“…Intracellular hyperglycemia induces PKC activity via increased levels of diacylglycerol (DAG) resulting mainly from DAG de novo synthesis [5,6]. Indirect PKC activation may be due to RAGE engagement or polyol pathway activation [5,6] or activation of 12/15-LO [7,8]. Various effects of PKC activation have been described which may promote atherogenesis.…”