GATA6 Controls Insulin Biosynthesis and Secretion in Adult β-Cells

Villamayor, Laura; Rodríguez-Seguel, Elisa; Araujo, Raquel; Carrasco, Manuel; Bru-Tarí, Eva; Mellado-Gil, José Manuel; Gauthier, Benoit R.; Martinelli, Paola; Quesada, Iván; Soria, Bernat; Martı́n, Franz; Cano, David A.; Rojas, Anabel

doi:10.2337/db17-0364

Cited by 29 publications

(32 citation statements)

References 42 publications

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“…Importantly, the expression of key transcriptional regulators of adult ß cell function such as Pdx1 , MafA , and Nkx6.1 was also diminished. Similar to what it is observed during pancreas embryonic development, GATA6 directly regulates the expression of Pdx1 in adult ß cells . Thus, the effects of GATA6 loss on adult ß cell function might be indirect.…”

Section: Role Of Gata Factors In Mouse Pancreas Formationsupporting

confidence: 62%

“…A recent study in Gata6 ‐deficient mice has demonstrated an important role for GATA6 in ß cell development and function. In this study, Gata6 was inactivated during early pancreas development using the mouse Pdx1‐Cre line . No pancreatic endocrine defects were observed in young Gata6 ‐deficient mice.…”

Section: Role Of Gata Factors In Mouse Pancreas Formationmentioning

confidence: 93%

“…However, as they age (6 months old), they develop glucose intolerance, a phenotype indicative of defects in ß cell function. Indeed, loss of GATA6 activity causes a vast array of abnormalities in adult ß cells including impairment of insulin biosynthesis and secretion, defects in mitochondrial ultrastructure, and disorganization of the endoplasmic reticulum (Figure ). These latter results are in agreement with an earlier study showing that GATA factors are required for endoplasmic reticulum integrity in mouse ß cells .…”

Section: Role Of Gata Factors In Mouse Pancreas Formationmentioning

confidence: 99%

“…Studies performed in isolated human islets also point to an important role for GATA6 in the response to endoplasmic reticulum stress . Loss of GATA6 has a broad impact on ß cell gene expression . Transcriptome analysis of Gata6 ‐deficient islets shows decreased expression of genes critical for different aspects of ß cell function including glucose sensing ( Slc2a2 , encoding for GLUT2 transporter), insulin biosynthesis ( Ins1 , Ins2 , and Pcsk1 ), and insulin secretion ( Abcc8 , Cacna1c , and SNAP‐25).…”

Section: Role Of Gata Factors In Mouse Pancreas Formationmentioning

confidence: 99%

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GATA factors in pancreas development and disease

2019

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There is an urgent need for the development of novel therapeutics options for diabetic patients given the high prevalence of diabetes worldwide and that, currently, there is no cure for this disease. The transplantation of pancreatic islets that contain insulin-producing cells is a promising therapeutic alternative, particularly for type 1 diabetes. However, the shortage of organ donors constitutes a major limitation for this approach; thus, developing alternative sources of insulin-producing cells is of critical importance. In the last decade, our knowledge of the molecular mechanisms controlling embryonic pancreas development has significantly advanced.More importantly, this knowledge has provided the basis for the in vitro generation of insulin-producing cells from stem cells. Recent studies have revealed that GATA transcription factors are involved in various stages of pancreas formation and in the adult ß cell function. Here, we review the fundamental role of GATA transcription factors in pancreas morphogenesis and their association with congenital diseases associated with pancreas.

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Section: Role Of Gata Factors In Mouse Pancreas Formationsupporting

confidence: 62%

Section: Role Of Gata Factors In Mouse Pancreas Formationmentioning

confidence: 93%

Section: Role Of Gata Factors In Mouse Pancreas Formationmentioning

confidence: 99%

Section: Role Of Gata Factors In Mouse Pancreas Formationmentioning

confidence: 99%

See 2 more Smart Citations

GATA factors in pancreas development and disease

2019

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“…The ability to explain additional clinical abnormalities that are associated with the underlying genetic cause is one of the major benefits of precision medicine. One such example is cardiac defects in patients with GATA6 mutations and remission of transient diabetes in patients with 6q24 methylation abnormalities [54]. …”

Section: Monogenic Diabetes: the Field Where Precision Diabetes Has Amentioning

confidence: 99%

Precision Diabetes Is Slowly Becoming a Reality

Mohan

Radha

2019

Med Princ Pract

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The concept of precision medicine is becoming increasingly popular. The use of big data, genomics and other “omics” like metabolomics, proteomics and transcriptomics could make the dream of personalised medicine become a reality in the near future. As far as polygenic forms of diabetes like type 2 and type 1 diabetes are concerned, interesting leads are emerging, but precision diabetes is still in its infancy. However, with regard to monogenic forms of diabetes like maturity-onset diabetes of the young and neonatal diabetes mellitus, rapid strides have been made and precision diabetes has already become part of the clinical tools used at advanced diabetes centres. In patients with some monogenic form of diabetes, if the appropriate gene defects are identified, insulin injections can be stopped and be replaced by oral sulphonylurea drugs. In the coming years, rapid advances can be expected in the field of precision diabetes, thereby making the control of diabetes more effective and hopefully leading to prevention of its complications and improvement of the quality of life of people afflicted with diabetes.

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Monogenic Diabetes with GATA6 Mutations: Characterization of a Novel Family and a Comprehensive Analysis of the GATA6 Clinical and Genetics Traits

et al. 2023

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Monogenic diabetes caused by GATA6 mutations were almost described as neonatal diabetes, and the phenotypic spectrum has expanded since then. Our study underscores the broad phenotypic spectrum by reporting a de novo GATA6 mutation in a family. Furthermore, we reviewed related literature to summarize the clinical and genetic characteristics of monogenic diabetes with GATA6 mutations (n = 39) in order to improve clinicians’ understanding of the disease. We conclude that the GATA6 missense mutation (c. 749G > T, p. Gly250Val) is not reported presently, characterized by adult-onset diabetes with pancreatic dysplasia and located in transcriptional activation region. Carries with GATA6 mutations (n = 55) have a variable spectrum of diabetes, ranging from neonatal (72.7%), childhood-onset (20%) to adults-onset (7.5%). 83.5% of patients with abnormal pancreatic development. Heart and hepatobillary defects are the most common abnormalities of extrapancreatic features. Most mutations with GATA6 are loss of function (LOF, 71.8%) and located in functional region. Functional studies mostly support loss-of-function as the pathophysiological mechanism. In conclusion, there are various types of diabetes with GATA6 mutations, which can also occur in adult diabetes. Phenotypic defects with GATA6 mutations are most frequently malformations of pancreas and heart. This highlights the importance of comprehensive clinical evaluation of identified carriers to evaluate their full phenotypic spectrum.

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GATA6 Controls Insulin Biosynthesis and Secretion in Adult β-Cells

Cited by 29 publications

References 42 publications

GATA factors in pancreas development and disease

GATA factors in pancreas development and disease

Precision Diabetes Is Slowly Becoming a Reality

Monogenic Diabetes with GATA6 Mutations: Characterization of a Novel Family and a Comprehensive Analysis of the GATA6 Clinical and Genetics Traits

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