Proinsulin C-peptide abrogates type-1 diabetes-induced increase of renal endothelial nitric oxide synthase in rats

2008 ◽  
Vol 24 (4) ◽  
pp. 331-338 ◽  
Author(s):  
Akihiro Kamikawa ◽  
Tatsuya Ishii ◽  
Kohei Shimada ◽  
Kennedy Makondo ◽  
Osamu Inanami ◽  
...  
2016 ◽  
Vol 14 (1) ◽  
pp. 33-39 ◽  
Author(s):  
William G Mayhan ◽  
Denise M Arrick

Our goal was to test the hypothesis that administration of tetrahydrobiopterin (BH4) would improve impaired endothelial nitric oxide synthase–dependent dilation of cerebral arterioles during type 1 diabetes. In addition, we examined the influence of BH4 on levels of superoxide in brain tissue. In vivo diameter of cerebral arterioles in nondiabetic and diabetic rats was measured in response to endothelial nitric oxide synthase–dependent agonists (acetylcholine and adenosine 5′-diphosphate) and an endothelial nitric oxide synthase–independent agonist (nitroglycerine) before and during application of BH4 (1.0 µM). We also measured levels of superoxide from cortex tissue in nondiabetic and diabetic rats under basal states and during BH4. Acetylcholine and adenosine 5′-diphosphate dilated cerebral arterioles in nondiabetic rats, but this vasodilation was significantly impaired in diabetic rats. In contrast, nitroglycerine produced similar vasodilation in nondiabetic and diabetic rats. Application of BH4 did not enhance vasodilation in nondiabetic rats but improved impaired cerebral vasodilation in diabetic rats. Basal superoxide levels were increased in cortex tissue from diabetic rats, and BH4 reduced these levels to that found in nondiabetic rats. Thus, BH4 is an important mediator of endothelial nitric oxide synthase–dependent responses of cerebral arterioles in diabetes and may have therapeutic potential for the treatment of cerebral vascular disease.


2008 ◽  
Vol 69 (4-5) ◽  
pp. 279-283 ◽  
Author(s):  
Emmanouil Galanakis ◽  
Diamantis Kofteridis ◽  
Kalliopi Stratigi ◽  
Eleni Petraki ◽  
Vassilios Vazgiourakis ◽  
...  

2009 ◽  
Vol 4 (4) ◽  
pp. 521-527 ◽  
Author(s):  
Constantina Heltianu ◽  
Simona-Adriana Manea ◽  
Cristian Guja ◽  
Alexandra Robciuc ◽  
Constantin Ionescu-Tirgoviste

AbstractMicrovascular complications associated with type 1 diabetes mellitus (T1DM) are caused in part by endothelial dysfunction. We aimed to determine the association between polymorphisms in endothelial nitric oxide synthase (eNOS) gene (894G>T, 4ab) and T1DM-associated microvascular disorders, and the roles of nitrite/nitrate products (NOx) and low molecular weight-AGEs (LMW-AGEs) levels in this relationship. We carried out a case-control study (328 subjects) and determined genotypes by PCR. The rare-type TT of eNOS 894G>T was significantly overrepresented in patients without microvascular disorders as compared with control (OR=3.64; 95% C.I.=1.02–12.73; P=0.039). The prevalence of neuropathy was high among 894GG homozygotes (OR=0.5; 95% C.I.=0.29–0.86; P=0.012) who had high levels of triglycerides, elevated systolic BP, increased NOx, and LMW-AGEs. Decreased NOx levels were associated with 894TT genotype (beta=−0.65; P=0.043) in diabetic patients prone to microvascular complications. Multiple regression analysis indicated a negative correlation between eNOS 894G>T and diabetic neuropathy (P=0.025). The distribution of eNOS 4aa genotype was high (P=0.042) in patients with T1DM; however, it does not represent a risk factor for neuropathy. The overrepresentation of eNOS 894TT genotype in diabetic patients is associated with low risk for neuropathy. Decreased NOx and LMW-AGEs levels and lower lipid profile are the main features of patients carrying the eNOS 894T allele. These data suggest that the eNOS 894TT genotype may play a protective role by preventing microvascular disorders.


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