Glucose and Blood Pressure-Dependent Pathways–The Progression of Diabetic Kidney Disease (original) (raw)
Related papers
Diabetic Kidney Disease: Pathophysiology and Therapeutic Targets
Journal of Diabetes Research, 2015
Diabetes is a worldwide epidemic that has led to a rise in diabetic kidney disease (DKD). Over the past two decades, there has been significant clarification of the various pathways implicated in the pathogenesis of DKD. Nonetheless, very little has changed in the way clinicians manage patients with this disorder. Indeed, treatment is primarily centered on controlling hyperglycemia and hypertension and inhibiting the renin-angiotensin system. The purpose of this review is to describe the current understanding of how the hemodynamic, metabolic, inflammatory, and alternative pathways are all entangled in pathogenesis of DKD and detail the various therapeutic targets that may one day play a role in quelling this epidemic.
Molecular signaling pathways of diabetic kidney disease; new concepts
2017
Diabetic kidney disease is a main cause of end-stage renal disease (ESRD), therefore, it is important to understand the molecular mechanism underlying diabetic kidney disease. Todays, various factors such as hemodynamic changes, molecular signaling and metabolic pathways have been shown to be involved in its pathogenesis. Excessive glucose influx stimulates cellular signaling pathways, containing advanced glycation end-products (AGEs), oxidative stress conditions, Rho-kinase, the diacylglycerol (DAG)-protein kinase C (PKC) pathway, polyol pathway and hexosamine pathway. In hyperglycemic condition, these factors cooperate with other aggravating factors. Then activated inflammatory processes lead to the development of glomerulosclerosis. The aim is to describe understanding of the signaling pathways in diabetic kidney disease. Core tip Excessive glucose influx stimulates cellular signaling pathways, including advanced glycation end-products (AGEs), oxidative stress conditions, Rho-kin...
Diabetic kidney disease is a main cause of end-stage renal disease (ESRD), therefore, it is important to understand the molecular mechanism underlying diabetic kidney disease. Todays, various factors such as hemodynamic changes, molecular signaling and metabolic pathways have been shown to be involved in its pathogenesis. Excessive glucose influx stimulates cellular signaling pathways, containing advanced glycation end-products (AGEs), oxidative stress conditions, Rho-kinase, the diacylglycerol (DAG)-protein kinase C (PKC) pathway, polyol pathway and hexosamine pathway. In hyperglycemic condition, these factors cooperate with other aggravating factors. Then activated inflammatory processes lead to the development of glomerulosclerosis. The aim is to describe understanding of the signaling pathways in diabetic kidney disease.
Review on pathophysiology and treatment of diabetic kidney disease
Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2010
Diabetes is the leading cause of chronic kidney disease, which in the Thailand is the most common cause of end stage renal disease (ESRD) requiring dialysis. Patients with diabetic kidney disease (DKD) are at a higher risk of mortality, mostly from cardiovascular complications, than other patients with diabetes. The development of DKD is determined by environmental and genetic factors. This review focuses on the latest published data dealing with mechanisms and treatment of DKD. DKD has several distinct phases of development of the disease and hyperglycemia-induced metabolic and hemodynamic pathways are recognized to be mediators of kidney disease. Multiple biochemical pathways have been postulated that explain how hyperglycemia causes tissue damage: nonenzymatic glycosylation that generates advanced glycosylation end products, activation of protein kinase C, and acceleration of the polyol pathway. Oxidative stress also seems to be a theme common pathway. These derangements, along w...
2018
Diabetic nephropathy (DN) is a major micro-vascular complication in diabetes mellitus (DM). One third of type 1 DM and 1/6 of type 2 DM develop DN account for more than 30% of total end stage renal disorders (ESRD), the main cause of renal replacement therapy. It is characterized by mesangial expansion, glomerulosclerosis and increased intracellular matrix accumulation. Injury of podocytes and reduced cellular density are considered to be root of the disease. Molecular mechanisms that leads diabetic patients toward nephropathy is hyperglycemia induced production of reactive oxygen species (ROS), advanced glycation end products (AGEs), activation of polyol pathway, increased expression of TGF-β, angiotensin II and aldosterone induced oxidative injury. DN can be prevented by controlling the glycemic levels, blood pressure, body weight and consumption of low protein diets along with high potassium supplementation. Therapeutic strategies including intensive glycemic control, blockage of...
Renal Disease in Diabetes Mellitus: Recent Studies and Potential Therapies
Journal of Diabetes & Metabolism, 2013
Diabetic kidney disease is the predominant cause of end stage kidney disease in North America, estimated to be 152 per million population in 2010. New guidelines published by KDIGO on Chronic Kidney Disease classification are discussed. In light of recent clinical trials, better insight has been gained on how improve management of diabetic patients to prevent renal disease and its progression, especially with regards to metabolic and blood pressure control. Unfortunately, studies of newer therapies such as endothelin 1 antagonists and bardoxolone methyl have been disappointing, but several other possible therapeutic agents are under investigation and may provide hope for patients with diabetes mellitus in the future.
International Journal of Experimental Pathology, 2012
Diabetes mellitus and hypertension often occur simultaneously. About 58% of subjects had hypertension at the time that they were diagnosed as having diabetes mellitus (Chen et al. 2011). In addition, 87.2% of African-American subjects with obesity and high-blood pressure exhibited insulin-resistance (Campbell et al. 2004). There is a general agreement that coexistence of diabetes and hypertension is associated with a higher cardiovascular risk and mortality in humans (Endemann et al. 2004; Colivicchi et al. 2008) and animal models (Hendriks et al. 1993; Ballo et al. 2010). Diabetes, either in human or animals, is associated with a number of changes in the cardiovascular system. Animal models of diabetes are associated with the impairment of endothelium-dependent relaxation (Matsumoto et al. 2007), unchanged endothelium-independent relaxation (Cameron & Cotter 1992), and increased (Taylor et al. 1994) or decreased (Hassan et al. 2011) contraction response to phen-ylephrine (PE). Moreover, human type 2 diabetes is associated with decreased basal and stimulated release of nitric oxide (NO) (Woodman et al. 2006). In addition, both human type 1 (Indran et al. 2004) and type 2 (Singhania et al. 2008) diabetes mellitus are associated with increased oxidative stress. Experimental models of hypertension are associated with cardiovascular changes. They are associated with impaired endothelium-dependent relaxation (Wheal & Randall 2009), impaired (Ajay et al. 2007) or intact (Pacher et al. 2002) endothelium-independent relaxation, and enhanced contraction response to PE (Ajay et al. 2007). Also, the models are associated with increased oxidative stress (Bauersachs et al. 1998) and have been linked to both decreased (Schä fer et al. 2004) and increased (Chang et al. 2002) NO availability and release. Despite a high rate of occurrence of both diabetes and hypertension in humans, the cardiovascular effects of the
Kidney International, 2002
group had an index of 0.06 Ϯ 0.01, the diabetic group was Cyclooxygenase-2 inhibitor blocks expression of mediators of 2.7 Ϯ 0.04 and the treated group was 0.6 Ϯ 0.03 (P Ͻ 0.0001 renal injury in a model of diabetes and hypertension. compared to the diabetic group). Background. We previously reported that renal cortical Conclusions. These results suggest that in an experimental cyclooxygenase (COX-2) expression increased following subtomodel of diabetes and hypertension, inhibition of COX-2 extal nephrectomy, and chronic treatment with a selective COX-2 inhibitor, SC58236, reduced proteinuria and retarded the depression decreases potential mediators of glomerular and tubuvelopment of glomerulosclerosis. The present studies were delointerstitial injury and also decreases biochemical, functional signed to examine the effects of COX-2 inhibition in a model and structural markers of renal injury. of diabetic nephropathy. Methods. Rats were divided into three groups: control, diabetic (streptozotocin-induced diabetic animals with superim-Previous studies have suggested that prostaglandins posed DOCA/salt hypertension; right nephrectomy and DOCA treatment), and treated (administration of the selective COX-2 may be involved in the development of diabetic nephropinhibitor, SC58236, to a subset of diabetic/DOCA/salt rats). athy. Increased urinary and glomerular prostaglandin Insulin was administered to maintain blood glucose in the 200 production has been reported in experimental models to 300 mg/dL range. of diabetes [1-5]. Prostaglandins have been implicated Results. Systolic blood pressure in the two diabetic groups as mediators of the alterations in renal hemodynamics was elevated within one week and remained elevated until sacrifice at six weeks (control, 108 Ϯ 2 mm Hg; diabetic, 158 Ϯ in early diabetes [3, 6, 7], and of increased mesangial 4 mm Hg; treated, 156 Ϯ 7 mm Hg). When measured at six 1 See Editorial by Zatz and Fujihara, p. 1091. macula densa cells and to a subset of medullary interstitial cells in the papilla [13]. In chronically salt depleted
Journal of Molecular and Genetic Medicine, 2014
Vascular complications in diabetes are an emergent health care problem. Accelerated endothelial dysfunction in pathological settings connoted by hyperlipidaemia and hyperglycaemia is a crucial step for the development and the progression of atherosclerosis. Previous data support the central role of Advanced Glycated End-products (AGEs) and oxidation or glycation of Low Dense Lipoproteins (LDLs) in the impaired vascular remodelling associated with diabetes. Hyperglycemia, via NADPH Oxidase (NOX) enzymatic activity, upholds the production of Reactive Oxygen Species (ROS), which in turn mediate tissue damage and long-lasting "metabolic memory". Nonetheless, in diabetic setting, ROS act as secondary messenger to strictly control stemness of visceral-derived adipose stem cells and to promote transcriptional and post-transcriptional events, also involving small non-coding microRNAs (miRs). In this article we provide an overview on the events elicited by acute and chronic hyperglycemia that account for vascular and kidney diseases. The deleterious effects of LDL and fatty acids on endothelial progenitor cells in condition connoted by hyperglycemia are also discussed. Moreover, as current therapeutic approaches failed to improve endothelial dysfunction/disease progression and consequently long-term outcomes in diabetics with vascular complications, particular attention has been devoted to describe efforts made to identify novel therapeutic options, for the management of one of the most relevant health care problems world wide. Finally, as targeting of epigenetic mechanisms is a future challenge, relevant data supporting their deep involvement in long-lasting "metabolic memory" have been also addressed.