Variations in the mRNA expression level of UDP-GlcNAc epimerase/ManNAc kinase and neuraminidase 1 genes in organs of type 2 diabetic animals

Inim, M.; Ibrahim, Mohammed Auwal; Isah, Murtala Bindawa; Onyike, Elewechi

doi:10.1007/s10719-021-09979-7

Cited by 4 publications

(4 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This indicates that elevated pancreatic sialic acid level may not be due to the influx of exogenous sialoglycoconjugates. In our previous study ( 23 ), the GNE gene expression was elevated in the pancreas of diabetic animals with a concomitant elevation in total sialic acid content of the organ. Since it has been previously demonstrated that sialyltransferases are insensitive to the rate of flux through the sialic acid biosynthetic pathway ( 34 ), the data in the present study also support increased endogenous synthesis of sialic acid by the pancreas rather than recycling of exogenous sialic acid.…”

Section: Discussionmentioning

confidence: 69%

“…These enzymes may thus be linked to some of the pathophysiological features of diabetes mellitus. In our recent study, we also observed an increase in the mRNA expression of NEU1 gene in some organs of T2D rats while the gene expression of UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase ( GNE ) was elevated in the pancreas, but not other organs ( 23 ). These suggest that the increased sialic acid level in the organs (except for pancreas) of diabetic rats could not be due to increased endogenous synthesis of sialic acid but probably due to increased recycling of glycoconjugates.…”

Section: Introductionmentioning

confidence: 76%

“…Both T1D and T2D are associated with increased output of sialic acid in the serum and some organs in humans and experimental animals ( 5 – 7 , 11 ). Increased de novo biosynthesis measured as the mRNA expression level of the rate determining enzyme ( GNE ), might not account for the observed increase of sialic acid level in most organs of diabetic animals ( 23 ). In this study, we reported that the activities of sialidase and sialyltransferase are modulated in serum and selected organs of diabetic rats and could be involved in the recycling of sialic acid depending on the organ, stage and type of diabetes.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Possible involvement of sialidase and sialyltransferase activities in a stage-dependent recycling of sialic acid in some organs of type 1 and type 2 diabetic rats

Erhabor,

Obochi,

Isah

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

BackgroundType 1 (T1D) and type 2 (T2D) diabetes lead to an aberrant metabolism of sialoglycoconjugates and elevated free serum sialic acid (FSSA) level. The present study evaluated sialidase and sialyltranferase activities in serum and some organs relevant to diabetes at early and late stages of T1D and T2D.MethodsSialic acid level with sialidase and sialyltransferase activities were monitored in the serum, liver, pancreas, skeletal muscle and kidney of diabetic animals at early and late stages of the diseases.ResultsThe FSSA and activity of sialidase in the serum were significantly increased at late stage of both T1D and T2D while sialic acid level in the liver was significantly decreased in the early and late stages of T1D and T2D, respectively. Furthermore, the activity of sialidase was significantly elevated in most of the diabetes-relevant organs while the activity of sialyltransferase remained largely unchanged. A multiple regression analysis revealed the contribution of the liver to the FSSA while pancreas and kidney contributed to the activity of sialidase in the serum.ConclusionsWe concluded that the release of hepatic sialic acid in addition to pancreatic and renal sialidase might (in)directly contribute to the increased FSSA during both types of diabetes mellitus.

show abstract

Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Possible involvement of sialidase and sialyltransferase activities in a stage-dependent recycling of sialic acid in some organs of type 1 and type 2 diabetic rats

Erhabor,

Obochi,

Isah

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…In these same studies, pharmacologic upregulation of NEU1 expression and activity with ambroxol in mice led to desialylation of the IR, increased IR Tyr phosphorylation and Akt signaling, and improved glucose tolerance and insulin resistance in mice exposed to a HFD. NEU1 expression was increased in the spleen, liver, and kidneys of streptozotocin (STZ)-treated diabetic rats ( 361 ). Similarly, NEU1 protein levels were increased in cardiomyocytes in the STZ mouse model of diabetic cardiomyopathy, and NEU1 silencing protected against STZ-induced cardiomyopathy and myocardial fibrosis, inflammation, and apoptosis through an AMPK-SIRT3 pathway ( 131 ).…”

Section: Neus and Mucs In Autoimmune Diseasesmentioning

confidence: 99%

Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond

2022

View full text Add to dashboard Cite

Mammalian neuraminidases (NEUs), also known as sialidases, are enzymes that cleave off the terminal neuraminic, or sialic, acid resides from the carbohydrate moieties of glycolipids and glycoproteins. A rapidly growing body of literature indicates that in addition to their metabolic functions, NEUs also regulate the activity of their glycoprotein targets. The simple post-translational modification of NEU protein targets—removal of the highly electronegative sialic acid—affects protein folding, alters protein interactions with their ligands, and exposes or covers proteolytic sites. Through such effects, NEUs regulate the downstream processes in which their glycoprotein targets participate. A major target of desialylation by NEUs are mucins (MUCs), and such post-translational modification contributes to regulation of disease processes. In this review, we focus on the regulatory roles of NEU-modified MUCs as coordinators of disease pathogenesis in fibrotic, inflammatory, infectious, and autoimmune diseases. Special attention is placed on the most abundant and best studied NEU1, and its recently discovered important target, mucin-1 (MUC1). The role of the NEU1 - MUC1 axis in disease pathogenesis is discussed, along with regulatory contributions from other MUCs and other pathophysiologically important NEU targets.

show abstract

The connections of sialic acids and diabetes mellitus: therapeutic or diagnostic value?

Ibrahim,

Isah,

Inim

et al. 2024

Glycobiology

View full text Add to dashboard Cite

Modulation of sialic acids is one of the important pathological consequences of both type 1 and type 2 diabetes mellitus with or without the micro- and macrovascular complications. However, the mechanistic, therapeutic and/or diagnostic implications of these observations are uncoordinated and possibly conflicting. This review critically analyses the scientific investigations connecting sialic acids with diabetes mellitus. Generally, variations in the levels and patterns of sialylation, fucosylation and galactosylation were predominant across various tissues and body systems of diabetic patients, but the immune system seemed to be most affected. These might be explored as a basis for differential diagnosis of various diabetic complications. Sialic acids are predominantly elevated in nearly all forms of diabetic conditions, particularly nephropathy and retinopathy, which suggests some diagnostic value but the mechanistic details were not unequivocal from the available data. The plausible mechanistic explanations for the elevated sialic acids are increased desialylation by sialidases, stimulation of hexosamine pathway and synthesis of acute phase proteins as well as oxidative stress. Additionally, sialic acids are also profoundly associated with glucose transport and insulin resistance in human-based studies while animal-based studies revealed that the increased desialylation of insulin receptors by sialidases, especially NEU1, might be the causal link. Interestingly, inhibition of the diabetes-associated NEU1 desialylation was beneficial in diabetes management and might be considered as a therapeutic target. It is hoped that the article will provide an informed basis for future research activities on the exploitation of sialic acids and glycobiology for therapeutic and/or diagnostic purposes against diabetes mellitus.

show abstract

Variations in the mRNA expression level of UDP-GlcNAc epimerase/ManNAc kinase and neuraminidase 1 genes in organs of type 2 diabetic animals

Cited by 4 publications

References 20 publications

Possible involvement of sialidase and sialyltransferase activities in a stage-dependent recycling of sialic acid in some organs of type 1 and type 2 diabetic rats

Possible involvement of sialidase and sialyltransferase activities in a stage-dependent recycling of sialic acid in some organs of type 1 and type 2 diabetic rats

Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond

The connections of sialic acids and diabetes mellitus: therapeutic or diagnostic value?

Contact Info

Product

Resources

About