Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adenosine (Ado) system may participate in regulation of kidney function in diabetes mellitus (DM), therefore we explored its role and interrelation with NO in the control of renal circulation and excretion in normoglycemic (NG) and streptozotocin-diabetic (DM) rats. Effects of theophylline (Theo), a non-selective Ado receptor antagonist, were examined in anaesthetized NG or in streptozotocin induced diabetic (DM) rats, untreated or after blockade of NO synthesis with l-NAME. We measured arterial blood pressure (MABP), whole kidney blood flow and renal regional flows: cortical and outer- and inner-medullary (IMBF), determined as laser-Doppler fluxes. Renal excretion of water, total solutes and sodium and in situ renal tissue NO signal (selective electrodes) were also determined. Theo experiments disclosed minor baseline vasoconstrictor and vasodilator tone in the kidney of NG and DM rats, respectively. NO blockade increased baseline MABP and decreased renal haemodynamics, similarly in NG and DM rats, indicating comparable vasodilator influence of NO in the two groups. Unexpectedly, in all rats with intact NO synthesis, Ado receptor blockade increased kidney tissue NO. In NO-deficient NG and DM rats, Ado receptor blockade induced comparable renal vasodilatation, suggesting similar vasoconstrictor influence of the Ado system. However, DM rats showed an unexplained association of decreased MABP and IMBF and increased NO signal. Higher baseline renal excretion in DM rats indicated inhibition of renal tubular reabsorption due to the prevalence of natriuretic A2 over antinatriuretic A1 receptors. In conclusion, the experiments provided new insights in functional interrelation of adenosine and NO in normoglycaemia and streptozotocin-diabetes.
Nitric Oxide 2020 11 01
PMID:Interplay of the adenosine system and NO in control of renal haemodynamics and excretion: Comparison of normoglycaemic and streptozotocin diabetic rats. 3282 41

The Kinin B2 receptor (B2R) is classically involved in vasodilation and inflammatory responses. However, through the observation of hypoglycemic effects of Angiotensin-I-Converting Enzyme (ACE) inhibitors, this protein has been related to metabolic glucose modulation in physiological and pathophysiological contexts. Although several studies have evaluated this matter, the different methodologies and models employed, combined with the distinct target organs, results in a challenge to summarize and apply the knowledge in this field. Therefore, this review aims to compile human and animal data in order to provide a big picture about what is already known regarding B2R and glucose metabolism, as well to suggest pending investigation issues aiming at evaluating the role of B2R in relation to glucose metabolism in homeostatic situations and metabolic disturbances. The data indicate that B2R signaling is involved mainly in glucose uptake in skeletal muscle and adipose tissue, acting as a synergic player beside insulin. However, most data indicate that B2R induces increased glucose oxidation, instead of storage, via activation of a broad signaling cascade involving Nitric Oxide (NO) and cyclic-GMP dependent protein kinase (PKG). Additionally, we highlight that this modulation is impaired in metabolic disturbances such as diabetes and obesity, and we provide a hypothetic mechanism to explain this blockade in light of literature data provided for this review, as well as other authors.
 ...
PMID:Bradykinin B2 Receptor Signaling Increases Glucose Uptake and Oxidation: Evidence and Open Questions. 3284 70

Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and devastating disease characterized by vascular smooth muscle and endothelial cell proliferation leading to a narrowing of the vessels in the lung. The increased resistance in the lung and the higher pressures generated result in right heart failure. Nitric Oxide (NO) deficiency is considered a hallmark of IPAH and altered function of endothelial nitric oxide synthase (eNOS), decreases NO production. We recently demonstrated that glucose dysregulation results in augmented protein serine/threonine hydroxyl-linked N-Acetyl-glucosamine (O-GlcNAc) modification in IPAH. In diabetes, dysregulated glucose metabolism has been shown to regulate eNOS function through inhibition of Ser-1177 phosphorylation. However, the link between O-GlcNAc and eNOS function remains unknown. Here we show that increased protein O-GlcNAc occurs on eNOS in PAH and Ser-615 appears to be a novel site of O-GlcNAc modification resulting in reduced eNOS dimerization. Functional characterization of Ser-615 demonstrated the importance of this residue on the regulation of eNOS activity through control of Ser-1177 phosphorylation. Here we demonstrate a previously unidentified regulatory mechanism of eNOS whereby the O-GlcNAc modification of Ser-615 results in reduced eNOS activity and endothelial dysfunction under conditions of glucose dysregulation.
 ...
PMID:Specific O-GlcNAc modification at Ser-615 modulates eNOS function. 3286 26


<< Previous 1 2 3 4 5 6 7