Hyperglycemia modulates angiotensinogen gene expression

Gabriely, Ilan; Yang, Xiao Man; Cases, Jane A.; Xi, Hui; Rossetti, Luciano; Barzilai, Nir

doi:10.1152/ajpregu.2001.281.3.r795

Cited by 56 publications

(45 citation statements)

References 36 publications

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“…While glucose augments AGT level, insulin promotes a decrease in its expression. These effects were found in the insulin-resistant state of obese rats (23). Our results indicate that Mas-KO mice exhibit an insulin-resistant state as evidenced by the decrease in insulin sensitivity and glucose tolerance, hyperinsulinemia, and, more importantly, by a decrease in insulin-induced glucose uptake in adipose tissue.…”

Section: Discussionsupporting

confidence: 59%

Mas Deficiency in FVB/N Mice Produces Marked Changes in Lipid and Glycemic Metabolism

Santos

Fernandes²,

Mario³

et al. 2008

Diabetes

227

184

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OBJECTIVE-Metabolic syndrome is characterized by the variable coexistence of obesity, hyperinsulinemia, insulin resistance, dyslipidemia, and hypertension. It is well known that angiotensin (Ang) II is importantly involved in the metabolic syndrome. However, the role of the vasodilator Ang-(1-7)/Mas axis is not known. The aim of this study was to evaluate the effect of genetic deletion of the G protein-coupled receptor, Mas, in the lipidic and glycemic metabolism in FVB/N mice. RESULTS-Despite normal body weight, Mas-knockout (Mas-KO) mice presented dyslipidemia, increased levels of insulin and leptin, and an ϳ50% increase in abdominal fat mass. In addition, Mas gene-deleted mice presented glucose intolerance and reduced insulin sensitivity as well as a decrease in insulin-stimulated glucose uptake by adipocytes and decreased GLUT4 in adipose tissue. Mas Ϫ/Ϫ presented increased muscle triglycerides, while liver triglyceride levels were normal. Expression of TGF-␤ and AGT genes was higher in Mas-KO animals in comparison with controls. RESEARCH DESIGN AND METHODS-Plasma CONCLUSIONS-These results show that

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Section: Discussionsupporting

confidence: 59%

Mas Deficiency in FVB/N Mice Produces Marked Changes in Lipid and Glycemic Metabolism

Santos

Fernandes²,

Mario³

et al. 2008

Diabetes

227

184

View full text Add to dashboard Cite

show abstract

“…21 The homozygous TT state was associated with approximately 20% increase in plasma AGT and elevated plasma AGT levels have been demonstrated in insulin-resistant states. 22 Consequently subjects with the AGT T allele might need higher doses of ACE inhibitors to achieve a similar effect on the incidence of diabetes compared to AGT MM homozygous subjects. However, we were not able to show this in our study.…”

Section: Discussionmentioning

confidence: 99%

Genetic variation in the renin-angiotensin system modifies the beneficial effects of ACE inhibitors on the risk of diabetes mellitus among hypertensives

et al. 2008

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The aim of this study was to assess whether the association between angiotensin-converting enzyme (ACE) inhibitor use and the incidence of treated diabetes mellitus is modified by genetic polymorphisms in the renin-angiotensin system (RAS).In a nested case-control study, treated hypertensive patients were genotyped for ACE (insertion (I)/deletion (D)), angiotensinogen (AGT; M235T) and angiotensin II type 1 receptor (AGTR1; A1166C). Cases of newly treated diabetes were identified based on pharmacy records and controls were not yet drug treated for diabetes (case:control ratio 1:10). Self-administered questionnaires and physical examinations were used to assess risk factors for diabetes mellitus. Logistic regression was used to calculate the relative risk of diabetes associated with ACE inhibitor use relative to other antihypertensive treatment, stratified by the RAS genotypes. Among 205 cases and 2050 controls, homozygous 1166A carriers of the AGTR1 gene had a significantly decreased incidence of diabetes associated with current use of ACE inhibitors (odds ratio, OR: 0.47; 95% CI: 0.26-0.84), whereas this incidence was increased among 1166C allele carriers (OR: 1.32; 95% CI: 0.81-2.14). The interaction OR was 3.21 (95% CI: 1.53-6.75). ACE I allele carriers had a significantly reduced incidence of diabetes associated with ACE inhibitors use (OR: 0.63; 95% CI: 0.41-0.98), whereas DD homozygotes had no reduced risk (OR: 0.95; 95% CI: 0.46-1.96). The risk of diabetes associated with ACE inhibitor use was not significantly modified by the AGT-M235T polymorphism. Treatment with ACE inhibitors in hypertensive subjects significantly reduces the occurrence of diabetes in homozygous 1166A carriers of the AGTR1 gene and carriers of the ACE I allele, but not in 1166C allele carriers of the AGTR1 gene and in homozygous ACE D allele carriers.

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“…In insulin-responsive tissues, both high glucose and glucosamine have been reported to increase angiotensinogen gene expression (66), providing a link between O-GlcNAc and enhanced angiotensin II formation. This may contribute to the elevated angiotensin II levels observed in diabetes that have been associated with increased oxidative damage and enhanced cardiomyocyte apoptosis and necrosis (61).…”

Section: O-glcnacylation and Cardiomyocyte Dysfunctionmentioning

confidence: 99%

ProteinO-GlcNAcylation: a new signaling paradigm for the cardiovascular system

Laczy¹,

Hill²,

Wang³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

143

135

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The posttranslational modification of serine and threonine residues of nuclear and cytoplasmic proteins by the O-linked attachment of the monosaccharide ␤-N-acetylglucosamine (O-GlcNAc) is a highly dynamic and ubiquitous protein modification. Protein O-GlcNAcylation is rapidly emerging as a key regulator of critical biological processes including nuclear transport, translation and transcription, signal transduction, cytoskeletal reorganization, proteasomal degradation, and apoptosis. Increased levels of O-GlcNAc have been implicated as a pathogenic contributor to glucose toxicity and insulin resistance, which are both major hallmarks of diabetes mellitus and diabetes-related cardiovascular complications. Conversely, there is a growing body of data demonstrating that the acute activation of O-GlcNAc levels is an endogenous stress response designed to enhance cell survival. Reports on the effect of altered O-GlcNAc levels on the heart and cardiovascular system have been growing rapidly over the past few years and have implicated a role for O-GlcNAc in contributing to the adverse effects of diabetes on cardiovascular function as well as mediating the response to ischemic injury. Here, we summarize our present understanding of protein O-GlcNAcylation and its effect on the regulation of cardiovascular function. We examine the pathways regulating protein O-GlcNAcylation and discuss, in more detail, our understanding of the role of O-GlcNAc in both mediating the adverse effects of diabetes as well as its role in mediating cellular protective mechanisms in the cardiovascular system. In addition, we also explore the parallels between O-GlcNAc signaling and redox signaling, as an alternative paradigm for understanding the role of O-GlcNAcylation in regulating cell function. hexosamine biosynthesis; protein O-glycosylation; ␤-N-acetylglucosamine transferase; diabetes mellitus POSTTRANSLATIONAL MODIFICATION (PTM) of proteins is a common mechanism for the modulation of protein function, location, and turnover. Although protein phosphorylation is probably the most widely studied form of PTM, there are many other PTMs, including acylation, ubiquitylation, methylation, acetylation, thiolation, nitration, and glycosylation (107). The focus of this review is protein glycosylation, specifically, O-glycosylation of nuclear and cytoplasmic proteins. Classical protein glycosylation occurs in the endoplasmic reticulum and Golgi, leading to the formation of stable and complex elongated oligosaccharide structures via both N-linkage on asparagine and O-linkage on the hydroxy amino acids serine and threonine in addition to hydroxyproline, hydroxylysine, and tyrosine residues of proteins that become secreted or membrane component glycoproteins (189). In contrast, glycosylation of nuclear and cytoplasmic proteins is a rapid and dynamic modification of serine or threonine residues by the O-linked attachment of the monosaccharide ␤-N-acetylglucosamine (OGlcNAc) (97,195); this process is referred to as protein O-GlcNAcylation to contrast it wi...

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Hyperglycemia modulates angiotensinogen gene expression

Cited by 56 publications

References 36 publications

Mas Deficiency in FVB/N Mice Produces Marked Changes in Lipid and Glycemic Metabolism

Mas Deficiency in FVB/N Mice Produces Marked Changes in Lipid and Glycemic Metabolism

Genetic variation in the renin-angiotensin system modifies the beneficial effects of ACE inhibitors on the risk of diabetes mellitus among hypertensives

ProteinO-GlcNAcylation: a new signaling paradigm for the cardiovascular system

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