Activating Transcription Factor 6 Polymorphisms and Haplotypes Are Associated with Impaired Glucose Homeostasis and Type 2 Diabetes in Dutch Caucasians

Meex, Steven J.R.; Greevenbroek, Marleen M.J. van; Ayoubi, Torik; Vlietinck, Robert; Vliet-Ostaptchouk, Jana V. van; Mh, Hofker; Vermeulen, Vicky M. M.-J.; Schalkwijk, Casper G.; Feskens, Edith J. M.; Boer, Jolanda M. A.; Stehouwer, Coen D. A.; Kallen, Carla; Bruin, T.W.A. de

doi:10.1210/jc.2006-2280

Cited by 48 publications

(28 citation statements)

References 16 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Single-nucleotide polymorphisms exist in a functionally important region of the ATF6α gene that is associated with type 2 diabetes in a population of Pima Indians (Thameem et al 2006), Dutch Caucasians (Meex et al 2007), and Chinese (Gonzalez-Rodriguez et al 2014). Moreover, high-fat diet (HFD)-fed Atf6α −/− mice displayed glucose intolerance, blunted insulin secretion, and reduced pancreatic insulin content due to β-cell failure (Usui et al 2012).…”

Section: Atf6αmentioning

confidence: 99%

Physiological/pathological ramifications of transcription factors in the unfolded protein response

2017

View full text Add to dashboard Cite

Numerous environmental, physiological, and pathological insults disrupt protein-folding homeostasis in the endoplasmic reticulum (ER), referred to as ER stress. Eukaryotic cells evolved a set of intracellular signaling pathways, collectively termed the unfolded protein response (UPR), to maintain a productive ER protein-folding environment through reprogramming gene transcription and mRNA translation. The UPR is largely dependent on transcription factors (TFs) that modulate expression of genes involved in many physiological and pathological conditions, including development, metabolism, inflammation, neurodegenerative diseases, and cancer. Here we summarize the current knowledge about these mechanisms, their impact on physiological/pathological processes, and potential therapeutic applications.

show abstract

Section: Atf6αmentioning

confidence: 99%

Physiological/pathological ramifications of transcription factors in the unfolded protein response

2017

View full text Add to dashboard Cite

show abstract

“…Genetic evidence that a defective UPR may be an important predisposing factor for the development type 2 diabetes in humans is somewhat limited, although genome-wide association studies have implicated polymorphisms within the ATF6 gene with type 2 diabetes in both Pima Indians and Dutch Caucasians (70,71). Moreover, polymorphisms within the Wolfram syndrome 1 (WFS1) gene, a negative regulator of ER stress (72), have also been associated with increased risk of type 2 diabetes (73).…”

Section: Diabetesdiabetesjournalsorg Herbert and Laybuttmentioning

confidence: 99%

A Reevaluation of the Role of the Unfolded Protein Response in Islet Dysfunction: Maladaptation or a Failure to Adapt?

Herbert

Laybutt

2016

Diabetes

View full text Add to dashboard Cite

Endoplasmic reticulum (ER) stress caused by perturbations in ER homeostasis activates an adaptive response termed the unfolded protein response (UPR) whose function is to resolve ER stress. If unsuccessful, the UPR initiates a proapoptotic program to eliminate the malfunctioning cells from the organism. It is the activation of this proapoptotic UPR in pancreatic β-cells that has been implicated in the onset of type 2 diabetes and thus, in this context, is considered a maladaptive response. However, there is growing evidence that β-cell death in type 2 diabetes may not be caused by a maladaptive UPR but by the inhibition of the adaptive UPR. In this review, we discuss the evidence for a role of the UPR in β-cell dysfunction and death in the development of type 2 diabetes and ask the following question: Is β-cell dysfunction the result of a maladaptive UPR or a failure of the UPR to adequately adapt? The answer to this question is critically important in defining potential therapeutic strategies for the treatment and prevention of type 2 diabetes. In addition, we discuss the potential role of the adaptive UPR in staving off type 2 diabetes by enhancing β-cell mass and function in response to insulin resistance.

show abstract

“…89 Thus, this raises the possibility that the interaction between WFS1 and ATF6 not only functions as a method to regulate the UPR, but also insulin biosynthesis: by restricting ATF6 activation, WFS1 prevents ATF6-mediated suppression of insulin gene expression.…”

Section: Type 1 and Type 2 Diabetes And The Er Stress Connectionmentioning

confidence: 99%

Stress hypERactivation in the β-cell

Fonseca

Urano²,

Burcin

et al. 2010

Islets

View full text Add to dashboard Cite

Activating Transcription Factor 6 Polymorphisms and Haplotypes Are Associated with Impaired Glucose Homeostasis and Type 2 Diabetes in Dutch Caucasians

Abstract: Our results strengthen the evidence that one or more variants in ATF6 are associated with disturbed glucose homeostasis and DM2.

Cited by 48 publications

References 16 publications

Physiological/pathological ramifications of transcription factors in the unfolded protein response

Physiological/pathological ramifications of transcription factors in the unfolded protein response

A Reevaluation of the Role of the Unfolded Protein Response in Islet Dysfunction: Maladaptation or a Failure to Adapt?

Stress hypERactivation in the β-cell

Contact Info

Product

Resources

About