Analysis of MGEA5 on 10q24.1–q24.3 encoding the β-O-linked N-acetylglucosaminidase as a candidate gene for type 2 diabetes mellitus in Pima Indians

Farook, Vidya S.; Bogardus, Clifton; Procházka, Michal

doi:10.1016/s1096-7192(02)00127-0

Cited by 31 publications

(18 citation statements)

References 25 publications

(31 reference statements)

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“…Farook et al (43) previously examined the MGEA5 gene as a candidate gene in the Pima Indians and reported no evidence to support its involvement in susceptibility to diabetes or insulin resistance. Based on SNP discovery efforts conducted on 30 subjects, that study identified only two variants in the gene regions that were screened.…”

Section: Discussionmentioning

confidence: 99%

A Single Nucleotide Polymorphism in MGEA5 Encoding O-GlcNAc–selective N-Acetyl-β-d Glucosaminidase Is Associated With Type 2 Diabetes in Mexican Americans

et al. 2005

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Section: Discussionmentioning

confidence: 99%

A Single Nucleotide Polymorphism in MGEA5 Encoding O-GlcNAc–selective N-Acetyl-β-d Glucosaminidase Is Associated With Type 2 Diabetes in Mexican Americans

et al. 2005

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“…Supporting a role for O-GlcNAc in the development of type II diabetes, mutations and alternative splice variants of O-GlcNAcase are associated with the onset of type II diabetes (40,92). Goto-Kakizaki rats express a 90-kDa isoform, ⌬250 -345, of O-GlcNAcase that appears to lack O-GlcNAcase activity (37).…”

Section: O-glcnacase Catalyzes the Removal Of O-glcnac (Ec 32152 mentioning

confidence: 99%

The roles ofO-linked β-N-acetylglucosamine in cardiovascular physiology and disease

Zachara

2012

American Journal of Physiology-Heart and Circulatory Physiology

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More than 1,000 proteins of the nucleus, cytoplasm, and mitochondria are dynamically modified by O-linked β- N-acetylglucosamine ( O-GlcNAc), an essential post-translational modification of metazoans. O-GlcNAc, which modifies Ser/Thr residues, is thought to regulate protein function in a manner analogous to protein phosphorylation and, on a subset of proteins, appears to have a reciprocal relationship with phosphorylation. Like phosphorylation, O-GlcNAc levels change dynamically in response to numerous signals including hyperglycemia and cellular injury. Recent data suggests that O-GlcNAc appears to be a key regulator of the cellular stress response, the augmentation of which is protective in models of acute vascular injury, trauma hemorrhage, and ischemia-reperfusion injury. In contrast to these studies, O-GlcNAc has also been implicated in the development of hypertension and type II diabetes, leading to vascular and cardiac dysfunction. Here we summarize the current understanding of the roles of O-GlcNAc in the heart and vasculature.

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“…Importantly, the genetic variation in the O-GlcNAase (Oga, also known as Mgea5) gene contributes to increased risk for type 2 diabetes [8]. However, in some populations, Oga is not significantly associated with type 2 diabetes [9].…”

Section: Introductionmentioning

confidence: 99%

Obesity resistance and increased energy expenditure by white adipose tissue browning in Oga +/- mice

et al. 2015

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Aims/hypothesis O-GlcNAcylation plays a role as a metabolic sensor regulating cellular signalling, transcription and metabolism. Transcription factors and signalling pathways related to metabolism are modulated by N-acetyl-glucosamine (OGlcNAc) modification. Aberrant regulation of OGlcNAcylation is closely linked to insulin resistance, type 2 diabetes and obesity. Current evidence shows that increased O-GlcNAcylation negatively regulates insulin signalling, which is associated with insulin resistance and type 2 diabetes. Here, we aimed to evaluate the effects of Oga (also known as Mgea5) haploinsufficiency, which causes hyper-OGlcNAcylation, on metabolism. Methods We examined whether Oga +/-mice developed insulin resistance. Metabolic variables were determined including body weight, glucose and insulin tolerance, metabolic rate and thermogenesis. Results Oga deficiency does not affect insulin signalling even at hyper-O-GlcNAc levels. Oga +/-mice are lean with reduced fat mass and improved glucose tolerance. Furthermore, Oga +/-mice resist high-fat diet-induced obesity with ameliorated hepatic steatosis and improved glucose metabolism. Oga haploinsufficiency potentiates energy expenditure through the enhancement of brown adipocyte differentiation from the stromal vascular fraction of subcutaneous white adipose tissue (WAT). Conclusions/interpretation Our observations suggest that O-GlcNAcase (OGA) is essential for energy metabolism via regulation of the thermogenic WAT program.

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Analysis of MGEA5 on 10q24.1–q24.3 encoding the β-O-linked N-acetylglucosaminidase as a candidate gene for type 2 diabetes mellitus in Pima Indians

Cited by 31 publications

References 25 publications

A Single Nucleotide Polymorphism in MGEA5 Encoding O-GlcNAc–selective N-Acetyl-β-d Glucosaminidase Is Associated With Type 2 Diabetes in Mexican Americans

A Single Nucleotide Polymorphism in MGEA5 Encoding O-GlcNAc–selective N-Acetyl-β-d Glucosaminidase Is Associated With Type 2 Diabetes in Mexican Americans

The roles ofO-linked β-N-acetylglucosamine in cardiovascular physiology and disease

Obesity resistance and increased energy expenditure by white adipose tissue browning in Oga +/- mice

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