The result should facilitate refined structural analysis and the development of new specific aldose reductase inhibitors for the treatment of diabetic complications.
It is proposed that the decrease in GLUT4 levels is a protective mechanism, sparing skeletal muscle from gaining glucose and experiencing diabetic complications, albeit at the expense of becoming insulin resistant.(ABSTRACT TRUNCATED AT 400 WORDS)
Since aldose reductase is the first and ratelimiting enzyme of the polyol pathway, it is predicted that restriction fragment length polymorphisms at the aldose reductase gene locus may influence catalytic activity and determine individual susceptibility to the diabetic complications.
In conclusion, the variation of CETP locus modulates the risk for diabetic complications in patients with NIDDM and the effect seems to be different between men and women.
One of the alleles (Z-2) was found to be associated with early onset of retinopathy in patients with non-insulin-dependent diabetes (P = 0.007), suggesting that aldose reductase or a gene in the close vicinity may be involved in the pathogenesis of this diabetic complication.
Our data using mutant Cu,Zn-SOD related to familial amyotrophic lateral sclerosis (FALS) suggest that glycation itself and ROI produced from the glycated proteins are involved in many diseases, including diabetic complications.
To assess the prevalence of diabetes complications and the severity of diabetes in kindreds with NIDDM linked to the MODY3 locus (chromosome 12q) and to compare these parameters with data obtained in glucokinase (GCK)-deficient and other-MODY (unlinked to any of the three known loci) families, as well as with data from families with a late age of onset of NIDDM.
These results suggest that NO may be an endogenous regulator of aldose reductase, and consequently the polyol pathway of glucose metabolism; which has been implicated in the pathogenesis of secondary diabetic complications.
In order to examine the prevalence of chronic diabetic complications in MODY3, we examined 57 carriers with HNF-1alpha mutations for the presence of micro- and macrovascular complications.
The identified protein is designated as RSOR because it is renal-specific with properties of an oxido-reductase, and like ALR2 it may be relevant in the renal complications of diabetes mellitus.
However, the HbA1c level of the light-to-moderate drinkers without diabetic complications in the inactive ALDH2 group was significantly higher and the incidence of 24 hr urinary C-peptide was higher than the respective level of the light-to-moderate drinkers without diabetic complications in the active ALDH2 group.
The identified protein is designated as RSOR because it is renal-specific with properties of an oxido-reductase, and like ALR2 it may be relevant in the renal complications of diabetes mellitus.
For this purpose we include 75 Caucasian diabetic patients (34 consecutive type I and 41 consecutive type II) without late diabetic complications.Lp(a) and PAI-1 were assessed by ELISA.
Our study suggests that the alterations of TGF-beta1 levels could be associated with the activity of autoimmune process leading to pancreatic B cells destruction and may have a role in the pathogenesis of diabetic complications, but further studies in humans are needed.
The data of this study reveal that enhanced catalase/SOD and catalase /PON ratios that are correlated with HbA1c levels are observed in diabetic patients; thus, these ratios may be used as markers of poor glycemic control and as risk factors in the development of diabetic complications.
Thus, AGE up-regulates the profibrotic and proangiogenic protein CTGF (IGFBP-rP2), a finding that may have significance in the development of diabetic complications.
Transcription factor maturity-onset diabetes of the young, caused by mutations in the hepatocyte nuclear factor genes HNF-1alpha, HNF-4alpha and HNF-1beta, and in insulin promoter factor-1 results in a progressive beta-cell defect with increasing treatment requirements and diabetic complications.
Aims of the study were: (i) to determine the prevalence of mutations C282Y and H63D in the HFE gene causing hereditary hemochromatosis in patients with type 2 diabetes mellitus and non-diabetics, (ii) to investigate the relationship among HFE genotypes, serum ferritin and glucose intolerance and (iii) to assess possible association of HFE mutations with the susceptibility to develop late diabetic complications in the Czech population.