Meal-dependent Regulation of Circulating Glycated Insulin in Type 2 Diabetic Subjects

McKillop, Aine; Lindsay, JR; Au, S.; Mahood, KI; O’Harte, Finbarr; Flatt, Peter R.; Pm, Bell

doi:10.1055/s-2006-925125

Cited by 6 publications

(3 citation statements)

References 17 publications

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“…Furthermore, there is clear evidence that glycation and AGEs lead to mitochondrial dysfunction [15,16] and impaired immune responses [17,18,19]. Glycation of growth factors such as platelet-derived growth factor (PDGF) [20] and insulin [21,22,23], as well as receptors such as nerve growth factor (NGF)-receptor [24], were reported to affect signaling functions.…”

Section: Introductionmentioning

confidence: 99%

Wnt Glycation Inhibits Canonical Signaling

Mittag

Schmidt

et al. 2019

Cells

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Glycation occurs as a non-enzymatic reaction between amino and thiol groups of proteins, lipids, and nucleotides with reducing sugars or α-dicarbonyl metabolites. The chemical reaction underlying is the Maillard reaction leading to the formation of a heterogeneous group of compounds named advanced glycation end products (AGEs). Deleterious effects have been observed to accompany glycation such as alterations of protein structure and function resulting in crosslinking and accumulation of insoluble protein aggregates. A substantial body of evidence associates glycation with aging. Wnt signaling plays a fundamental role in stem cell biology as well as in regeneration and repair mechanisms. Emerging evidence implicates that changes in Wnt/β-catenin pathway activity contribute to the aging process. Here, we investigated the effect of glycation of Wnt3a on its signaling activity. Methods: Glycation was induced by treatment of Wnt3a-conditioned medium (CM) with glyoxal (GO). Effects on Wnt3a signaling activity were analyzed by Topflash/Fopflash reporter gene assay, co-immunoprecipitation, and quantitative RT-PCR. Results: Our data show that GO-treatment results in glycation of Wnt3a. Glycated Wnt3a suppresses β-catenin transcriptional activity in reporter gene assays, reduced binding of β-catenin to T-cell factor 4 (TCF-4) and extenuated transcription of Wnt/β-catenin target genes. Conclusions: GO-induced glycation impairs Wnt3a signaling function.

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Section: Introductionmentioning

confidence: 99%

Wnt Glycation Inhibits Canonical Signaling

Mittag

Schmidt

et al. 2019

Cells

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“…Following the transport of glucose into the pancreatic beta cell via Glut-2 glucose transporters, insulin is rapidly glycated during the stages of cellular insulin biosynthesis and storage. These glycated proteins have been identified in the pancreatic beta cell in animal and cellular models of diabetes [40][41][42][43] and recent human studies have confirmed the pancreatic beta cell as a highly favourable environment for glycation [44][45][46][47]. Increasing evidence supports a role for glycated insulin in the insulin resistant state of type 2 diabetes [48,49].…”

Section: Evaluation Of Glycaemic Status In Diabetesmentioning

confidence: 95%

Recent Developments in the Search for Biomarkers for the Diagnosis and Monitoring of Diabetes

McKillop¹,

Flatt

2008

EMI

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In the fields of genomic, proteomic and metabolomic technologies many advances have been made in the past few years for the early diagnosis and monitoring of diseases such as diabetes mellitus. As diabetes is afflicting affluent and developing societies throughout the world and is fuelled by aging demographics and the recent increase of obesity and related insulin resistance, there is a clear need to discover effective agents for diagnosing the disease and controlling glycaemic status. Biological markers such as peptides, proteins, metabolites, nucleic acids and polymorphisms have been proposed as novel exciting biomarkers. Patents have been filed demonstrating altered levels of proteins such as pancreatic polypeptide in beta cell failure and fibronectin and futuin-A in insulin resistance. Much interest has focused on the potential of glycosylated proteins such as glycated insulin, glycosylated amylin, C-terminally truncated form of the receptor for advanced glycation end-products, and glycated LDL antibodies. The emergence of genomic analysis is now complemented by systems biology and computational methods that can unravel large amounts of heterogeneous genetic and genomic information to produce meaningful results. Many patents have been filed that claim to estimate the susceptibility or predisposition of metabolic disease such as diabetes. New genomic technologies such as transcriptional profiling and proteomics have been shown to be significant in identifying and validating biomarkers, and systems biology has shown great promise in unravelling the complexities of genomic, proteomic and metabolomic technologies.

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“…Although the mechanisms of AGE-induced pancreatic β -cell dysfunction have to be further clarified, evidence indicates that AGEs interfere with several steps of the insulin-mediated regulation of glucose: AGEs inhibit the production of ATP needed for insulin secretion and decrease the expression of proteins involved in exocytosis of the insulin granules. Moreover, it has been demonstrated that glycation of insulin occurs during diabetes, and that glycated insulin represents a significant proportion of total circulating insulin in type 2 diabetes [82, 83]. Animal studies using isolated muscle and adipose tissue suggest that insulin glycation is associated with a significant compromise of its biological activity.…”

Section: Ages Activate Injury Pathways In Diabetic Pathophysiologymentioning

confidence: 99%

An Emerging Role of Glucagon-Like Peptide-1 in Preventing Advanced-Glycation-End-Product-Mediated Damages in Diabetes

Puddu

Mach

Nencioni

et al. 2013

Mediators of Inflammation

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Glucagon-like peptide-1 (GLP-1) is a gut hormone produced in the intestinal epithelial endocrine L cells by differential processing of the proglucagon gene. Released in response to the nutrient ingestion, GLP-1 plays an important role in maintaining glucose homeostasis. GLP-1 has been shown to regulate blood glucose levels by stimulating glucose-dependent insulin secretion and inhibiting glucagon secretion, gastric emptying, and food intake. These antidiabetic activities highlight GLP-1 as a potential therapeutic molecule in the clinical management of type 2 diabetes, (a disease characterized by progressive decline of beta-cell function and mass, increased insulin resistance, and final hyperglycemia). Since chronic hyperglycemia contributed to the acceleration of the formation of Advanced Glycation End-Products (AGEs, a heterogeneous group of compounds derived from the nonenzymatic reaction of reducing sugars with free amino groups of proteins implicated in vascular diabetic complications), the administration of GLP-1 might directly counteract diabetes pathophysiological processes (such as pancreatic β-cell dysfunction). This paper outlines evidence on the protective role of GLP-1 in preventing the deleterious effects mediated by AGEs in type 2 diabetes.

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Meal-dependent Regulation of Circulating Glycated Insulin in Type 2 Diabetic Subjects

Cited by 6 publications

References 17 publications

Wnt Glycation Inhibits Canonical Signaling

Wnt Glycation Inhibits Canonical Signaling

Recent Developments in the Search for Biomarkers for the Diagnosis and Monitoring of Diabetes

An Emerging Role of Glucagon-Like Peptide-1 in Preventing Advanced-Glycation-End-Product-Mediated Damages in Diabetes

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