Glucose and Insulin Treatment of Insulinoma Cells Results in Transcriptional Regulation of a Common Set of Genes

Ohsugi, Mitsuru; Cras-Méneur, Corentin; Zhou, Yongxia; Warren, Wesley C.; Bernal-Mizrachi, Ernesto; Permutt, M. A.

doi:10.2337/diabetes.53.6.1496

Cited by 47 publications

(45 citation statements)

References 48 publications

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“…Rem2 expression is induced by glucose treatment in MIN6 cells, a pancreatic β-islet cell line [23], a change that suppresses insulin secretion. Similarly, Gem/Kir expression is induced in the same cell line under elevated glucose, or following insulin and KCl treatment [28]. Rem2 is upregulated in developing neurons and siRNA-mediated Rem2 silencing profoundly inhibits the development of glutamatergic and GABAergic synapses [30].…”

Section: Transcriptional Regulationmentioning

confidence: 99%

“…Among the most unique features of RGK proteins is their ability to be transcriptionally regulated [3,5,6,11,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] (Table 2). Indeed, Gem/Kir was discovered as a gene upregulated in human T cells after stimulation with mitogens [5] or in BCR-Abl-transformed B cells [11].…”

Section: Transcriptional Regulationmentioning

confidence: 99%

“…Indeed, Gem/Kir was discovered as a gene upregulated in human T cells after stimulation with mitogens [5] or in BCR-Abl-transformed B cells [11]. Subsequent studies have found Gem to be induced following cytokine stimulation [36], in response to muscarinic receptor agonists [26], by glucose in pancreatic β-cell lines [28], during acute inflammation [37], and in the brains of tau-deficient mice (see below) [29]. Finally, Gem/ Kir expression has been correlated, via ribozyme-mediated knockdown, to cell invasiveness [38], a key feature of metastatic cancer.…”

Section: Transcriptional Regulationmentioning

confidence: 99%

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The RGK family of GTP-binding proteins: Regulators of voltage-dependent calcium channels and cytoskeleton remodeling

Correll¹,

Pang²,

Niedowicz³

et al. 2008

Cellular Signalling

100

136

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RGK proteins constitute a novel subfamily of small Ras-related proteins that function as potent inhibitors of voltage-dependent (VDCC) Ca 2+ channels and regulators of actin cytoskeletal dynamics. Within the larger Ras superfamily, RGK proteins have distinct regulatory and structural characteristics, including nonconservative amino acid substitutions within regions known to participate in nucleotide binding and hydrolysis and a C-terminal extension that contains conserved regulatory sites which control both subcellular localization and function. RGK GTPases interact with the VDCC β-subunit (Ca V β) and inhibit Rho/Rho kinase signaling to regulate VDCC activity and the cytoskeleton respectively. Binding of both calmodulin and 14-3-3 to RGK proteins, and regulation by phosphorylation controls cellular trafficking and the downstream signaling of RGK proteins, suggesting that a complex interplay between interacting protein factors and trafficking contribute to their regulation.

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Section: Transcriptional Regulationmentioning

confidence: 99%

Section: Transcriptional Regulationmentioning

confidence: 99%

Section: Transcriptional Regulationmentioning

confidence: 99%

See 1 more Smart Citation

The RGK family of GTP-binding proteins: Regulators of voltage-dependent calcium channels and cytoskeleton remodeling

Correll¹,

Pang²,

Niedowicz³

et al. 2008

Cellular Signalling

100

136

View full text Add to dashboard Cite

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“…By employing gene expression profiling with endocrine pancreas cDNAs microarrays, we noted that glucose and insulin regulated the transcription of a common set of genes in MIN6 cells within 45 min (Fig. 5A) (61). When glucose-regulated genes in IRKD⌬80 cells were analyzed, 112 of 125 genes previously activated in MIN6-Con cells were no longer activated by glucose.…”

Section: Con(e)mentioning

confidence: 99%

Reduced Expression of the Insulin Receptor in Mouse Insulinoma (MIN6) Cells Reveals Multiple Roles of Insulin Signaling in Gene Expression, Proliferation, Insulin Content, and Secretion

Ohsugi

Cras-Méneur

Zhou

et al. 2005

Journal of Biological Chemistry

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The role of insulin signaling in pancreatic ␤ cells has become increasingly apparent. Stably transformed insulinoma cell lines (MIN6) were created with small interfering RNA resulting in the reduction of insulin receptor (IR) expression up to 80% (insulin receptor knockdown, IRKD⌬80). Functionally perturbed IR signaling was confirmed with the absence of insulin-stimulated insulin receptor substrate 1 tyrosine phosphorylation. Additionally, Akt phosphorylation was reduced and responded poorly to glucose stimulation. Gene expression profiling revealed that reduced IR expression was associated with alterations in expression of >1,500 genes with diverse functions. IRKD cells exhibited low rate of proliferation due to delay in transition from G 0 /G 1 to S phase, whereas susceptibility to apoptosis did not differ from that of control cells. Insulin content was reduced in proportion to the reduction of IR. IRKD cells maintained glucose responsiveness as measured by NAD(P)H generation, whereas Ca 2؉ responses and insulin secretion were enhanced. IRKD⌬80 and control cells were treated with glucose (25 mM) or insulin (100 nM) for 45 min, and gene expression profiles were assessed. Transcriptional activation of several hundred early response genes common to both glucose and insulin stimulation was observed in control cells. In IRKD⌬80 cells, insulin failed to activate any genes as anticipated. Importantly, glucose stimulation of gene expression in IRKD⌬80 cells showed that most genes previously activated by glucose were no longer activated, suggesting a major autocrine/paracrine effect of insulin on glucoseregulated gene expression. On the other hand, there were a number of glucose-regulated genes in the IRKD⌬80 cells that were not previously observed in control cells, suggesting a feedback regulation of insulin signaling on glucose-regulated gene expression. These results demonstrate important roles of the insulin receptor in islet ␤ cell gene expression and function and may serve to elucidate molecular defects in animal models with diminished ␤ cell insulin signaling.Pancreatic ␤ cells dynamically adapt to their environment (1, 2). Changes in plasma glucose concentration along with various hormones and growth factors have been shown to be major determinants of insulin secretion, biosynthesis, and islet mass (3, 4). The islet ␤ cell responds to these changes in its environment by altering its transcriptional responses, and these changes in gene expression ultimately result in altered mass and function. However, the signaling pathways activated by these environmental changes and the ensuing transcriptional events that mediate these biological responses are only beginning to be elucidated. Specifically, the relationships between the signaling pathways activated by glucose and those activated by growth factors such as insulin remain unclear.The roles of insulin as a growth factor in the modulation of ␤ cell mass and function have been implied by the results of recent experiments. Glucose stimulation of ␤ cells in culture ha...

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“…Beta cells contain two candidates that meet these criteria, insulin and γ-aminobutyric acid (GABA). Much is known about the systemic role of insulin signalling in growth, and recent evidence also suggests that insulin mediates local beta cell growth responses [4,7]. In addition, mounting evidence implicates GABA, predominantly viewed as a neurotransmitter, as an evolutionarily conserved regulator of survival and growth processes [8].…”

Section: Introductionmentioning

confidence: 99%

Regulation of pancreatic islet cell survival and replication by γ-aminobutyric acid

et al. 2007

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Aims/hypothesis Pancreatic islets have evolved remarkable, though poorly understood mechanisms to modify beta cell mass when nutrient intake fluctuates or cells are damaged. We hypothesised that appropriate and timely adjustments in cell number occur because beta cells release proliferative signals to surrounding cells when stimulated by nutrients and 'bleed' these growth factors upon injury. Materials and methods In rat pancreatic islets, we measured DNA content, insulin content, insulin secretion after treatment, immunoblots of apoptotic proteins and the uptake of nucleoside analogues to assess the ability of γ-aminobutyric acid (GABA), which is highly concentrated in beta cells, to act as a growth and survival factor. This focus is supported by work from others demonstrating that GABA increases cell proliferation in the developing nervous system, acts as a survival factor for differentiated neurons and, interestingly, protects plants under stress. Results Our results show that DNA, insulin content and insulin secretion are higher in freshly isolated islets treated with GABA or GABA B receptor agonists. Exposure to GABA upregulated the anti-apoptotic protein B-cell chronic lymphocytic leukaemia XL and limited activation of caspase 3 in islets. The cellular proliferation rate in GABA-treated islets was twice that of untreated controls. Conclusions/interpretation We conclude that GABA serves diverse purposes in the islet, meeting a number of functional criteria to act as an endogenous co-regulator of beta cell mass.

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Glucose and Insulin Treatment of Insulinoma Cells Results in Transcriptional Regulation of a Common Set of Genes

Cited by 47 publications

References 48 publications

The RGK family of GTP-binding proteins: Regulators of voltage-dependent calcium channels and cytoskeleton remodeling

The RGK family of GTP-binding proteins: Regulators of voltage-dependent calcium channels and cytoskeleton remodeling

Reduced Expression of the Insulin Receptor in Mouse Insulinoma (MIN6) Cells Reveals Multiple Roles of Insulin Signaling in Gene Expression, Proliferation, Insulin Content, and Secretion

Regulation of pancreatic islet cell survival and replication by γ-aminobutyric acid

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