Short term exposure of beta cells to low concentrations of interleukin-1β improves insulin secretion through focal adhesion and actin remodeling and regulation of gene expression.

ABSTRACT We have investigated the ability of dexamethasone to regulate interleukin-1β (IL-1β)-induced gene expression, histone acetyltransferase (HAT) and histone deacetylase (HDAC) activity. Low concentrations of dexamethasone (10−10 M) repress IL-1β-stimulated granulocyte-macrophage colony-stimulating factor (GM-CSF) expression and fail to stimulate secretory leukocyte proteinase inhibitor expression. Dexamethasone (10−7 M) and IL-1β (1 ng/ml) both stimulated HAT activity but showed a different pattern of histone H4 acetylation. Dexamethasone targeted lysines K5 and K16, whereas IL-1β targeted K8 and K12. Low concentrations of dexamethasone (10−10 M), which do not transactivate, repressed IL-1β-stimulated K8 and K12 acetylation. Using chromatin immunoprecipitation assays, we show that dexamethasone inhibits IL-1β-enhanced acetylated K8-associated GM-CSF promoter enrichment in a concentration-dependent manner. Neither IL-1β nor dexamethasone elicited any GM-CSF promoter association at acetylated K5 residues. Furthermore, we show that GR acts both as a direct inhibitor of CREB binding protein (CBP)-associated HAT activity and also by recruiting HDAC2 to the p65-CBP HAT complex. This action does not involve de novo synthesis of HDAC protein or altered expression of CBP or p300/CBP-associated factor. This mechanism for glucocorticoid repression is novel and establishes that inhibition of histone acetylation is an additional level of control of inflammatory gene expression. This further suggests that pharmacological manipulation of of specific histone acetylation status is a potentially useful approach for the treatment of inflammatory diseases.

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Interference of Mycoplasma Infection in a Gene Expression Study: It Was the Environment and Not the Gene

Applied and Environmental Microbiology ◽

10.1128/aem.01265-10 ◽

2010 ◽

Vol 76 (23) ◽

pp. 7867-7869 ◽

Cited By ~ 2

Author(s):

Gregor Hoermann ◽

Joachim Spergser ◽

Elisa Einwallner ◽

Athanasios Makristathis ◽

Andrea Perne ◽

...

Keyword(s):

Gene Expression ◽

Gene Product ◽

Maximum Level ◽

Gene Activity ◽

Gene Expression Study ◽

Mycoplasma Infection ◽

Expression Study ◽

Short Term ◽

Short Term Exposure ◽

Inducible Gene

ABSTRACT We show that short-term exposure to doxycycline, as used in tetracycline-inducible gene expression models, protects cells from stress-induced death in cultures infected with Mycoplasma arginini. Coinciding with the expected maximum level of gene activity, antimicrobial effects of tetracyclines might be mistaken for antiapoptotic properties of the expressed gene product.

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Islet Gene View - a tool to facilitate islet research

10.1101/435743 ◽

2018 ◽

Cited By ~ 2

Author(s):

Olof Asplund ◽

Petter Storm ◽

Vikash Chandra ◽

Emilia Ottosson-Laakso ◽

Gad Hatem ◽

...

Keyword(s):

Gene Expression ◽

Type 2 Diabetes ◽

Insulin Secretion ◽

Pancreatic Islets ◽

Genetic Variants ◽

Scientific Community ◽

Regulation Of Gene Expression ◽

Web Resource ◽

Islet Hormones

AbstractChanges in the hormone-producing pancreatic islets are central culprits in type 2 diabetes (T2D) pathogenesis. Characterization of gene expression in islets how it is altered in T2D are therefore vital in understanding islet function and T2D pathogenesis. We leveraged RNA-sequencing and genome-wide genotyping in islets from 188 donors to create the Islet Gene View (IGW) platform to make this information easily accessible to the scientific community. The IGW combines expression data for a given gene with phenotypical data such as T2D status, BMI, HbA1c, insulin secretion, purity of islets, etc.), regulation of gene expression by genetic variants e.g., expression quantitative trait loci (eQTLs) and relationship with expression of islet hormones. In IGW, 285 differentially expressed genes (DEGs) were identified in T2D donors islets compared to controls. Forty percent of the DEGs showed cell-type enrichment and a large proportion of them were significantly co-expressed with islet hormone-encoding genes like glucagon (GCG, 56%), amylin (IAPP, 52%), insulin (INS, 44%) and somatostatin (SST, 24%). Inhibition of two DEGs, UNC5D and SERPINE2 impaired glucose-stimulated insulin secretion and impacted cell survival in a human beta-cell model.Significance StatementWe present Islet Gene View (IGW), a web resource facilitating information on gene expression in human pancreatic islets from organ donors easily accessible to the scientific community. In IGW, we explored RNA expression from 188 donor-islets and examined their relationship with islet phenotypes including insulin secretion and expression of genes encoding islet hormones. GWAS have shown 403 genetic variants associated with risk of type 2 diabetes (T2D) risk, however, the target genes and function of these variants in islets are largely unknown. By linking T2D risk variants to expression in islets from T2D and non-diabetic donors as well as islet phenotypes, use of IGW provided new insight into mechanisms by which variants in these loci may increase risk of T2D.

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Time and dose dependencies for priming effect of glucose on insulin secretion

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1981.240.1.e24 ◽

1981 ◽

Vol 240 (1) ◽

pp. E24-E31 ◽

Cited By ~ 6

Author(s):

V. Grill

Keyword(s):

Protein Synthesis ◽

Insulin Secretion ◽

Priming Effect ◽

Rest Period ◽

Short Term ◽

Priming Effects ◽

Perfused Rat Pancreas ◽

Rat Pancreas ◽

Short Term Exposure ◽

Effect Of Glucose

Short-term exposure to glucose increases insulin secretion during subsequent stimulation. This priming effect of glucose was further investigated in the perfused rat pancreas. A 5-min pulse of 27.7 mM glucose enhanced the response to a second pulse of the sugar after a 5- or 30-min period of 3.9 mM glucose. With a 10-min pulse of 27.7 mM glucose, the priming effect tended to persist also after a 60-min but not after a 90-min rest period. The priming effects of glucose were also evaluated from enhancement of stimulation 15 min later with 3-isobutyl-l-methylxanthine (IBMX). A 10-min pulse of 8.3 and 27.7, but not 5.6 mM glucose enhanced IBMX-induced insulin secretion. Cycloheximide did not abolish the priming effect of glucose on IBMX-induced insulin secretion. Conclusions are 1) priming is rapidly induced; 2) it persists longer than the time of induction; 3) threshold concentrations of glucose that induce priming are similar to those that initiate insulin secretions; and 4) mechanisms causing priming may not involve protein synthesis.

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