Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Hong Kong, the prevalence of diabetes is estimated to be 2% in the young population. In the diabetic population, 30% of patients have diagnosis before the age of 40 years. Besides, 30% of young diabetic patients have varying degrees of albuminuria. Mutations in the gene encoding the hepatocyte nuclear factor (HNF)-1beta are associated with a subtype of maturity-onset diabetes of the young (MODY 5) characterized by urogenital abnormalities. We examined 74 unrelated Chinese subjects with young-onset diabetes complicated by nephropathy for variants in this gene. The HNF-1beta gene was screened by direct sequencing and the functional properties of wild-type and mutant proteins were analyzed by transactivation analysis.A novel variant in exon 3 (E260D) was found in one patient. Extended family analysis revealed four other siblings carrying this variant. One subject had diabetes and another had impaired glucose tolerance. Another sibling had microalbuminuria but normal glucose tolerance. Transfection studies showed insignificant differences in transactivation ability between wild-type and mutated HNF-1beta. A silent polymorphism Q378Q was identified in another unrelated subject. These results suggest genetic variants in HNF-1beta are not a common cause of young-onset diabetes or diabetic nephropathy in Chinese, but may modify disease manifestation and progression. Other potential candidate genes should be looked for to account for the high prevalence of young-onset diabetes and nephropathy in this population.
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PMID:Genetic variants of hepatocyte nuclear factor-1beta in Chinese young-onset diabetic patients with nephropathy. 1458 83

Microalbuminuria is a marker for diabetic nephropathy. It also signifies cardiovascular disease, as well as nephropathy, in type 2 diabetes (DM2). Microalbuminuria may precede DM2, occurring with the insulin resistance syndrome and its components, including obesity and hypertension. Other indicators of cardiovascular risk, such as markers of inflammation, are associated with microalbuminuria in populations of patients with and without diabetes. With the rising prevalence of DM2 in minority youth, especially in Native Americans, a marker for future disease risk would allow earlier prevention strategies to be tested. Before microalbuminuria can be used in a prevention strategy, more needs to be known about the mechanism(s) of the association between elevated excretion, its relationship to glucose intolerance, and its relative contribution to cardiovascular and renal disease. These questions are especially applicable as we begin to observe the long-term complications of diabetes in youth.
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PMID:Microalbuminuria as a marker of cardiovascular and renal risk in type 2 diabetes mellitus: a temporal perspective. 1476 31

Peroxisome proliferator-activated receptors (PPAR) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Three PPAR isoforms, designated PPARalpha, -beta/delta, and -gamma, have been identified and attracted enormous attention as a result of the key role that these receptors play in regulating adipogenesis, lipid metabolism, insulin sensitivity, inflammation, and BP. Growing evidence points to a causative relationship between PPAR activity and the metabolic syndrome, including insulin resistance, glucose intolerance or type 2 diabetes, obesity, dyslipidemia, hypertension, atherosclerosis, and albuminuria. Importantly, both PPAR-alpha activators, such as the fibric acid class of hypolipidemic drugs, and PPAR-gamma agonists, including antidiabetic thiazolidinediones, have been proved to be effective for improving diverse aspects of the metabolic syndrome. All three PPAR isoforms seem to play important roles in the development of diabetic nephropathy in type 2 diabetes. Accumulating data suggesting that PPAR may serve as potential therapeutic targets for treating the metabolic syndrome and its related renal complications have begun to emerge. This article reviews the literature pertaining to the action, ligand selectivity, and physiologic role of PPAR. Particular emphasis is placed on their pathogenic roles in the metabolic syndrome and the therapeutic utility of PPAR modulators in the treatment of diabetic nephropathy.
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PMID:Peroxisome proliferator-activated receptor family and its relationship to renal complications of the metabolic syndrome. 1550 33

Pioglitazone (PIO) has preventive effects on impaired glucose tolerance (IGT) and urinary albumin excretion in diabetes. These effects in the early stage of diabetic nephropathy have not been fully described. Endothelial constitutive nitric oxide synthase (ecNOS) might be one of the mechanisms of glomerular hyperfiltration. The objective of the present study was to evaluate the effect of PIO, including the role of ecNOS on the early stage of diabetic nephropathy in KK/Ta mice. KK/Ta mice were given PIO (10 mg/kg/d) started at 12 or 16 weeks of age for 8 or 4 weeks, respectively. They were divided into 3 groups as follows: early treatment (n = 8), late treatment (n = 8), and control group (n = 12). The urinary albumin/creatinine ratio (ACR), fasting and casual blood glucose levels, ratio of glomerular and Bowman's capsule volume (GB ratio), and systemic blood pressure were measured as phenotypic characterizations. The ecNOS and iNOS protein expression in glomeruli were evaluated by immunofluorescence. PIO, especially early treatment, improved the ACR and the GB ratio, and ecNOS protein expression was decreased in the endothelium of glomerular vessels. The iNOS protein was not detectable. There were no significant changes in the levels of fasting and casual blood glucose and systemic blood pressure among all groups. We conclude that the effect of PIO on microalbuminuria might not be due to changing systemic blood pressure and blood glucose levels. It appears that the decrease of urinary albumin excretion might be related to improvement of glomerular enlargement, including hyperfiltration, since the levels of ecNOS protein were reduced by PIO in the glomerular vessels.
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PMID:Effect of pioglitazone on the early stage of type 2 diabetic nephropathy in KK/Ta mice. 1553 4

New-onset diabetes after renal transplantation (PTDM), a common consequence of immunosuppression, is associated with reduced patient survival. However, we know little about the impact of less marked changes in glucose homeostasis. To investigate this problem, we used data on average random blood glucose values during the first, second, and third months posttransplantation, derived from a cohort of 1186 patients who received their first cadaveric or living-donor transplant between 1984 and 2002. We analyzed both patient and death-censored graft survivals, subgrouping recipients into those with end-stage renal failure due to diabetic nephropathy versus those with PTDM versus patients without diabetes. We confirmed that PTDM patients display reduced survival following transplantation, but a long-term survival similar to that of patients with diabetic nephropathy and end-stage renal disease. However, among patients without diabetes, random blood glucose was also a strong determinant of outcome, even when in the low normal range. In contrast, neither the presence of diabetes nor random glucose levels showed a significant impact on graft survival. PTDM is recognized to be an important, potentially modifiable, risk factor for cardiovascular disease in transplant recipients. Our data suggest that there is a gradation of increased risk associated with impaired glycemic control that affects patients who do not have diabetes. These data support the need for improved understanding of glycemic control in transplant recipients and for more detailed screening for impaired glucose tolerance in this population.
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PMID:Random blood glucose measurements and survival in nondiabetic renal transplant recipients. 1568 82

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand--activated transcription factors. Three PPAR isoforms , designated PPARalpha, -beta/delta, and -gamma, have been identified and attracted enormous attention due to the key role these receptors play in regulating adipogenesis, lipid metabolism, insulin sensitivity, inflammation and blood pressure. Growing evidence points to a causative relationship between PPAR activity and the metabolic syndrome, including insulin resistance, glucose intolerance or type II diabetes, obesity, dyslipidemia, hypertension, atherosclerosis, and albuminuria. Importantly, both PPARalpha activators such as fibric acid class of hypolipidemic drugs and PPARgamma agonists including antidiabetic thiazolidinediones (TZDs) have been proved to be effective for improving metabolic syndrome. All three PPAR isoforms appear to play important roles in the development of type II diabetes and diabetic nephropathy. Accumulating data has begun to emerge suggesting PPARs may serve as potential therapeutic targets for treating the metabolic syndrome and its related complications. Here we review the literature pertaining to the action, ligand selectivity and physiological role of PPARs. Particular emphasis is placed on their pathogenic roles in the metabolic syndrome and the therapeutic utility of PPAR modulators in the treatment of type II diabetes.
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PMID:[PPAR family and its relationship to metabolic syndrome]. 1588 36

Extracts from Rhei Rhizoma extracts (RR) have been reported to attenuate metabolic disorders such as diabetic nephropathy, hypercholesterolemia and platelet aggregation. With this study we investigated the anti-diabetic action of 70% ethanol RR extract in streptozotocin-induced diabetic mice, and determined the action mechanism of active compounds of RR in vitro. In the diabetic mice, serum glucose levels at fasting and post-prandial states and glucose area under the curve at modified oral glucose tolerance tests were lowered without altering serum insulin levels, indicating that RR contained potential anti-diabetic agents. The fractions fractionated from RR extracts by XAD-4 column revealed that 60%, 80% and 100% methanol fractions enhanced insulin sensitivity and inhibited alpha-glucoamylase activity. The major compounds of these fractions were sennosides, rhein and rhaponticin. Rhaponticin and rhein enhanced insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Rhaponticin increased adipocytes with a differentiating effect similar to pioglitazone, but rhein and sennoside B decreased triglyceride accumulation. Sennoside A and B inhibited alpha-glucoamylase activity as much as acarbose. In conclusion, a crude extract of RR improves glucose intolerance by enhancing insulin-stimulated glucose uptake and decreasing carbohydrate digestion via inhibiting alpha-glucoamylase activity. Rhein and rhaponticin are potential candidates for hypoglycemic agents.
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PMID:Insulin sensitizing and alpha-glucoamylase inhibitory action of sennosides, rheins and rhaponticin in Rhei Rhizoma. 1618 18

The duration of diabetes mellitus and presence of hyperglycemia appear to be important in the development of diabetic nephropathy. Here, we present three patients with edema, heavy proteinuria, chronic renal failure, in whom no past or present symptomatic glucose intolerance or diabetic retinopathy were found. The kidney biopsy of these patients showed diffuse glomerular basement membrane thickening and nodular glomerulosclerosis, which resembled diabetic nephropathy. The renal function of these patients deteriorated rapidly and renal replacement therapy started later in the average of 11 months since the first visiting. These cases were diagnosed as diabetic nodular glomerulosclerosis, although there was no obvious evidence for diabetes. The absence of overt diabetes and diabetic retinopathy at presentation of nodular glomerulosclerosis in these cases does not refute the hypothesis that metabolic consequence of hyperglycemia is a prerequisite for the pathogenesis of diabetic microangiopathy, but some factors other than hyperglycemia may be responsible for renal damage in our patients. The modifiable risk factors in such a condition are postulated and discussed.
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PMID:Nodular glomerulosclerosis mimicking diabetic nephropathy without overt diabetes mellitus. 1624 Sep 2

Eicosapentaenoic acid (EPA) has been reported to have beneficial effects on the progression of various renal diseases including diabetic nephropathy; however, the precise mechanisms are not completely understood. We examined the effects of EPA on the early stage of type 2 diabetic nephropathy in KKA(y)/Ta mice and the possible role of inflammation, oxidative stress, and growth factor in this process. KKA(y)/Ta mice were divided into 2 groups. The treatment group was injected with EPA ethyl ester at 1 g/kg per day intraperitoneally from 12 to 20 weeks of age and the control group was injected with saline. Renal morphologic examinations were performed after 8 weeks of treatment. Glomerular macrophage infiltration and expression of monocyte chemoattractant protein 1, malondialdehyde (MDA), nitrotyrosine, transforming growth factor beta1 (TGF-beta1), and type I collagen were evaluated. Eicosapentaenoic acid decreased the levels of urinary albumin, serum triglyceride and MDA, and improved glucose intolerance in KKA(y)/Ta mice. Morphometric analysis showed that accumulation of extracellular matrix and the tubulointerstitial fibrosis area were significantly decreased after treatment. Immunohistochemistry revealed that glomerular macrophage infiltration and the expression of MDA and nitrotyrosine in KKA(y)/Ta mice were increased and were inhibited by EPA treatment. Protein and gene expression levels of monocyte chemoattractant protein 1, TGF-beta1, and type I collagen, which were evaluated by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction, were down-regulated in the EPA treatment group. In conclusion, EPA improves type 2 diabetic nephropathy in KKA(y)/Ta mice. This beneficial effect might be mediated by attenuation of metabolic abnormalities and inhibition of renal inflammation, oxidative stress, and TGF-beta expression.
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PMID:Effects of eicosapentaenoic acid on the early stage of type 2 diabetic nephropathy in KKA(y)/Ta mice: involvement of anti-inflammation and antioxidative stress. 1714 29

Pancreatic bi-hormones insulin and glucagon are the Yin and Yang in the regulation of glucose metabolism and homoeostasis. Insulin is synthesized primarily by pancreatic beta-cells and is released in response to an increase in blood glucose levels (hyperglycaemia). By contrast, glucagon is synthesized by pancreatic alpha-cells and is released in response to a decrease in blood glucose (hypoglycaemia). The principal role of glucagon is to counter the actions of insulin on blood glucose homoeostasis, but it also has diverse non-hyperglycaemic actions. Although Type 1 diabetes is caused by insulin deficiency (insulin-dependent) and can be corrected by insulin replacement, Type 2 diabetes is a multifactorial disease and its treatment is not dependent on insulin therapy alone. Type 2 diabetes in humans is characterized by increased insulin resistance, increased fasting blood glucose, impaired glucose tolerance and the development of glomerular hyperfiltration and microalbuminuria, ultimately leading to diabetic nephropathy and end-stage renal disease. Clinical studies have suggested that an inappropriate increase in hyperglycaemic glucagon (hyperglucagonaemia) over hypoglycaemic insulin (not insulin deficiency until advanced stages) plays an important role in the pathogenesis of Type 2 diabetes. However, for decades, research efforts and resources have been devoted overwhelmingly to studying the role of insulin and insulin-replacement therapy. By contrast, the implication of glucagon and its receptor signalling in the development of Type 2 diabetic metabolic syndromes and end-organ injury has received little attention. The aim of this review is to examine the evidence as to whether glucagon and its receptor signalling play any role(s) in the pathogenesis of Type 2 diabetic renal injury, and to explore whether targeting glucagon receptor signalling remains only a theoretical antidiabetic strategy in Type 2 diabetes or may realize its promise in the future.
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PMID:Targeting glucagon receptor signalling in treating metabolic syndrome and renal injury in Type 2 diabetes: theory versus promise. 1762 14


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