Regulation of beta cell replication

Lee, Ying C.; Nielsen, Jens Høiriis

doi:10.1016/j.mce.2008.08.033

Cited by 49 publications

(37 citation statements)

References 124 publications

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“…The replication of β-cells is controlled by a network of cell-cycle regulators [26][27][28]. VIMP deficiency in MIN6 cells induces G1 cell cycle arrest, which is related to imbalance of cell-cycle regulators.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of VCP-Interacting Membrane Selenoprotein (VIMP) Leads to G1 Cell Cycle Arrest and Cell Death in MIN6 Insulinoma Cells

Men

Sun

Ren

2018

Cell Physiol Biochem

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Background/Aims: VCP-interacting membrane selenoprotein (VIMP), an ER resident selenoprotein, is highly expressed in β-cells, however, the role of VIMP in β-cells has not been characterized. In this study, we studied the relationship between VIMP deficiency and β-cell survival in MIN6 insulinoma cells. Methods: To determine the role of VIMP in β-cells, lentiviral VIMP shRNAs were used to knock down (KD) expression of VIMP in MIN6 cells. Cell death was quantified by propidium iodide (PI) staining followed by flow cytometric analyses using a FACS Caliber and FlowJo software. Cell apoptosis and proliferation were determined by TUNEL assay and Ki67 staining, respectively. Cell cycle was analyzed after PI staining. Results: The results show that 1) VIMP suppression induces β-cell apoptosis, which is associated with a decrease in Bcl-xL, and the β-cell apoptosis induced by VIMP suppression can be inhibited by overexpression of Bcl-xL; 2) VIMP knockdown (KD) decreases cell proliferation and G1 cell cycle arrest by accumulating p27 and decreasing E2F1; 3) VIMP KD suppresses unfolded protein response (UPR) activation by regulating the IRE1α and PERK pathways; 4) VIMP KD increases insulin secretion. Conclusion: These results suggest that VIMP may function as a novel regulator to modulate β-cell survival, proliferation, cell cycle, UPR and insulin secretion in MIN6 cells.

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Section: Discussionmentioning

confidence: 99%

Deficiency of VCP-Interacting Membrane Selenoprotein (VIMP) Leads to G1 Cell Cycle Arrest and Cell Death in MIN6 Insulinoma Cells

Men

Sun

Ren

2018

Cell Physiol Biochem

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“…Adult rat islets are less responsive to mitogenic stimuli than neonatal rat islets. This is partly due to high production levels of factors associated with beta cell differentiation and inhibition of proliferation such as MAFA and P27 [8,10]. Thus, the lack of GAS6 effects in adult rat beta cells could be due to the abundance of such factors.…”

Section: Discussionmentioning

confidence: 99%

“…At the time around birth a dramatic increase in beta cell mass occurs [7,8]. The expansion arises from the proliferation of existing beta cells and by neogenesis from progenitor cells and declines after birth [9,10].…”

Section: Introductionmentioning

confidence: 99%

Growth arrest specific protein (GAS) 6: a role in the regulation of proliferation and functional capacity of the perinatal rat beta cell

et al. 2013

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Aims/hypothesis Maternal low-protein (LP) diet during gestation results in a reduced beta cell mass in the offspring at birth and this may hamper the ability to adapt to high-energy food and sedentary lifestyle later in life. To investigate the biology behind the LP-offspring phenotype, this study aimed to identify differentially expressed genes in the pancreas and their potential role in the fetal programming. Methods Wistar rats were given either an LP diet or normalchow (NC) diet during gestation and differentially expressed genes in the offspring around the time of birth were identified using RNA microarray and quantitative PCR. The role of a differentially expressed gene, growth arrest specific protein 6 (GAS6), was evaluated in vitro using neonatal rat islets.Results The mRNA level of Gas6, known to be mitogenic in other tissues, was reduced in LP offspring. The mRNA content of Mafa was increased in LP offspring suggesting an early maturation of beta cells. When applied in vitro, GAS6 increased proliferation of neonatal pancreatic beta cells, while reducing glucose-stimulated insulin secretion without changing the total insulin content of the islets. In addition, GAS6 decreased the mRNA content of Mafa. Conclusions/interpretation We propose a role for GAS6 in the regulation of pancreatic beta cells in the critical period around the time of birth. Our results support the hypothesis that the reduced beta cell mass seen in LP offspring is caused by a change in the intra-uterine environment that favours premature maturation of the beta cells.Keywords Fetal programming . Growth arrest specific protein 6 (GAS6) . Pancreatic beta cells

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“…It is believed that the mammalian pancreas maintains the required number of b-cells primarily through proliferation of existing b-cells. 10,[50][51][52][53] This supposition has been strongly supported by work from Dor et al 9 using a lineage tracing mouse model to demonstrate that the majority of b-cells are derived from previously differentiated b-cells. In addition, the authors went on to show that in response to pancreatic damage by partial pancreatectomy, the regeneration of b-cell mass occurs largely by the replication of pre-existing b-cells.…”

Section: Ngn3 In Pancreas Regeneration: Ductal Neogenesis and Transdimentioning

confidence: 90%

Neurogenin3: A master regulator of pancreatic islet differentiation and regeneration

Rukstalis¹,

Habener²

2009

Islets

117

118

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Regulation of beta cell replication

Cited by 49 publications

References 124 publications

Deficiency of VCP-Interacting Membrane Selenoprotein (VIMP) Leads to G1 Cell Cycle Arrest and Cell Death in MIN6 Insulinoma Cells

Deficiency of VCP-Interacting Membrane Selenoprotein (VIMP) Leads to G1 Cell Cycle Arrest and Cell Death in MIN6 Insulinoma Cells

Growth arrest specific protein (GAS) 6: a role in the regulation of proliferation and functional capacity of the perinatal rat beta cell

Neurogenin3: A master regulator of pancreatic islet differentiation and regeneration

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