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

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Taneera, JalalUniversity of Sharjah (author)

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

Article/chapterEnglish2019

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Elsevier BV,2019

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LIBRIS-ID:oai:lup.lub.lu.se:89ffa343-cca7-40b5-a760-a936561130ab
https://lup.lub.lu.se/record/89ffa343-cca7-40b5-a760-a936561130abURI
https://doi.org/10.1016/j.gene.2019.144028DOI

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Language:English
Summary in:English

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BACKGROUND: Type 2 diabetes (T2D) is a complex polygenic disease with unclear mechanism. In an attempt to identify novel genes involved in β-cell function, we harness a bioinformatics method called Loss-of-function tool (LoFtool) gene score. METHODS: RNA-sequencing data from human islets were used to cross-reference genes within the 1st quartile of most intolerant LoFtool score with the 100th most expressed genes in human islets. Out of these genes, GNAS and EEF1A1 genes were selected for further investigation in diabetic islets, metabolic tissues along with their correlation with diabetic phenotypes. The influence of GNAS and EEF1A1 on insulin secretion and β-cell function were validated in INS-1 cells. RESULTS: A comparatively higher expression level of GNAS and EEF1A1 was observed in human islets than fat, liver and muscle tissues. Furthermore, diabetic islets displayed a reduced expression of GNAS, but not of EEF1A, compared to non-diabetic islets. The expression of GNAS was positively correlated with insulin secretory index, GLP1R, GIPR and inversely correlated with HbA1c. Diabetic human islets displayed a reduced cAMP generation and insulin secretory capacity in response to glucose. Moreover, siRNA silencing of GNAS in INS-1 cells reduced insulin secretion, insulin content, and cAMP production. In addition, the expression of Insulin, PDX1, and MAFA was significantly down-regulated in GNAS-silenced cells. However, cell viability and apoptosis rate were unaffected. CONCLUSION: LoFtool is a powerful tool to identify genes associated with pancreatic islets dysfunction. GNAS is a crucial gene for the β-cell insulin secretory capacity.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
GNAS
Human pancreatic islets
INS-1 cells
Insulin secretion
RNA sequencing
siRNA silencing

Added entries (persons, corporate bodies, meetings, titles ...)

Dhaiban, SarahUniversity of Sharjah (author)
Mohammed, Abdul KhaderUniversity of Sharjah (author)
Mukhopadhyay, DebasmitaUniversity of Sharjah (author)
Aljaibeji, HayatUniversity of Sharjah (author)
Sulaiman, NabilUniversity of Sharjah (author)
Fadista, JoaoLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Danish Serum Institute, Copenhagen(Swepub:lu)med-jft (author)
Salehi, AlbertLund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups(Swepub:lu)farm-sal (author)
University of SharjahTranslationell muskelforskning (creator_code:org_t)

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In:Gene: Elsevier BV7151879-00380378-1119

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By the author/editor: Taneera, Jalal; Dhaiban, Sarah; Mohammed, Abdul ...; Mukhopadhyay, De ...; Aljaibeji, Hayat; Sulaiman, Nabil; show more...; Fadista, Joao; Salehi, Albert; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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