GNAS gene is an important regulator of insulin secretory capacity in pancreatic β-cells

Taneera, Jalal; Dhaiban, Sarah; Mohammed, Abdul Khader; Mukhopadhyay, Debasmita; Aljaibeji, Hayat; Sulaiman, Nabil; Fadista, João; Salehi, Albert

doi:10.1016/j.gene.2019.144028

Cited by 25 publications

(30 citation statements)

References 56 publications

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“…GNAS has been shown to be a highly expressed gene in pancreatic β cells . An association between GNAS expression and changes in pancreatic β cell function has also been demonstrated .…”

Section: Discussionmentioning

confidence: 97%

“…13 GNAS has been shown to be a highly expressed gene in pancreatic β cells. 6,14 An association between GNAS expression and changes in pancreatic β cell function has also been demonstrated. 15 However, Taneera et al showed that reduced and not increased GNAS expression in pancreatic β cells resulted in a decrease in the G sα subunit and reduced intracellular cAMP production.…”

Section: Discussionmentioning

confidence: 97%

“…showed that reduced and not increased GNAS expression in pancreatic β cells resulted in a decrease in the G sα subunit and reduced intracellular cAMP production. This led to the impairment of insulin exocytosis and secretion, with reduced insulin secretory capacity in response to glucose, and increased susceptibility to T2DM …”

Section: Discussionmentioning

confidence: 99%

“…This led to the impairment of insulin exocytosis and secretion, with reduced insulin secretory capacity in response to glucose, and increased susceptibility to T2DM. 14 Studies of patients with MAS have also shown abnormalities in pancreatic β cell architecture. 15,16 Furthermore, activating GNAS mutations in codon 201 have been reported in pancreatic tumors, specifically in intraductal papillary mucinous neoplasms (IPMNs).…”

Section: Discussionmentioning

confidence: 99%

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McCune–Albright syndrome and type 1 diabetes mellitus: a novel presentation

Chatty

Khattab

Marshall

2020

Annals of the New York Academy of Sciences

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McCune–Albright syndrome (MAS) is caused by postzygotic somatic activating mutations of GNAS and is classically characterized by the clinical triad of peripheral precocious puberty, café‐au‐lait pigmentation, and polyostotic fibrous dysplasia. It can also present with other hyperfunctioning endocrinopathies, including growth hormone excess, hyperprolactinemia, hypercortisolemia, hyperthyroidism, and renal phosphate wasting due to excess fibroblast growth factor 23. We review the clinical, biochemical, radiological, and genetic findings in a 7‐year‐old girl diagnosed with MAS at age 4 and then with autoimmune type 1 diabetes mellitus at age 7. While MAS is associated with hyperglycemia secondary to growth hormone excess and hypercortisolemia, an association with diabetes mellitus has not been demonstrated. We review the unique presentation of a patient with these two rare conditions.

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“…GNAS has been shown to be a highly expressed gene in pancreatic β cells . An association between GNAS expression and changes in pancreatic β cell function has also been demonstrated .…”

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

McCune–Albright syndrome and type 1 diabetes mellitus: a novel presentation

Chatty

Khattab

Marshall

2020

Annals of the New York Academy of Sciences

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“…5B). Within SC-beta 1 population, the upregulated genes of APH treated cells included GNAS, an important gene for beta cell insulin secretory capacity and function 39 ; ERO1LB, a beta cell enriched gene that is involved in insulin processing 40 ; ONECUT2, a transcription factor and increased with age in beta cells 41 ; and TTR, which has a positive role in glucose stimulated insulin release 42 . TPI1, a gene acting in glycolysis, was decreased in APH-treated cells ( Fig.…”

Section: Transcriptome Analysis Shows An Increase In Endocrine Cells mentioning

confidence: 99%

Establishing cell-intrinsic limitations in cell cycle progression controls graft growth and promotes differentiation of pancreatic endocrine cells

Sui

Egli

Xin

et al. 2020

Preprint

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Limitations in cell proliferation are a key barrier to reprogramming differentiated cells to pluripotent stem cells, and conversely, acquiring these limitations may be important to establish the differentiated state. The pancreas, and beta cells in particular have a low proliferative potential, which limits regeneration, but how these limitations are established is largely unknown.Understanding proliferation potential is important for the safty of cell replacement therapy with 2 cell products made from pluripotent stem cell which have unlimited proliferative potential. Here we test a novel hypothesis, that these limitations are established through limitations in S-phase progression. We used a stem cell-based system to expose differentiating stem cells to small molecules that interfere with cell cycle progression either by inducing G1 arrest, impairing Sphase entry, or S-phase completion. Upon release from these molecules, we determined growth potential, differentiation and function of insulin-producing endocrine cells both in vitro and after grafting in vivo. We found that the combination of G1 arrest with a compromised ability to complete DNA replication promoted the differentiation of pancreatic progenitor cells towards insulin-producing cells, improved the stability of the differentiated state, and protected mice from diabetes without the formation of cystic growths. Therefore, a compromised ability to enter S-phase and replicate the genome is a functionally important property of pancreatic endocrine differentiation, and can be exploited to generate insulin-producing organoids with predictable growth potential after transplantation.

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Beta‐Cell Tipe1 Orchestrates Insulin Secretion and Cell Proliferation by Promoting Gαs/cAMP Signaling via USP5

Ding,

Sun,

Liang

et al. 2024

Advanced Science

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Inadequate β‐cell mass and insulin secretion are essential for the development of type 2 diabetes (T2D). TNF‐α‐induced protein 8‐like 1 (Tipe1) plays a crucial role in multiple diseases, however, a specific role in T2D pathogenesis remains largely unexplored. Herein, Tipe1 as a key regulator in T2D, contributing to the maintenance of β cell homeostasis is identified. The results show that the β‐cell‐specific knockout of Tipe1 (termed Ins2‐Tipe1BKO) aggravated diabetic phenotypes in db/db mice or in mice with high‐fat diet‐induced diabetes. Notably, Tipe1 improves β cell mass and function, a process that depends on Gαs, the α subunit of the G‐stimulating protein. Mechanistically, Tipe1 inhibited the K48‐linked ubiquitination degradation of Gαs by recruiting the deubiquitinase USP5. Consequently, Gαs or cAMP agonists almost completely restored the dysfunction of β cells observed in Ins2‐Tipe1BKO mice. The findings characterize Tipe1 as a regulator of β cell function through the Gαs/cAMP pathway, suggesting that Tipe1 may emerge as a novel target for T2D intervention.

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GNAS gene is an important regulator of insulin secretory capacity in pancreatic β-cells

Cited by 25 publications

References 56 publications

McCune–Albright syndrome and type 1 diabetes mellitus: a novel presentation

McCune–Albright syndrome and type 1 diabetes mellitus: a novel presentation

Establishing cell-intrinsic limitations in cell cycle progression controls graft growth and promotes differentiation of pancreatic endocrine cells

Beta‐Cell Tipe1 Orchestrates Insulin Secretion and Cell Proliferation by Promoting Gαs/cAMP Signaling via USP5

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