Insight into Insulin Secretion from Transcriptome and Genetic Analysis of Insulin-Producing Cells of Drosophila

<p>In <em>Pseudomonas aeruginosa</em>, the orphan two-component sensor SagS contributes to both, the transition to biofilm formation and to biofilm cells gaining their heightened tolerance to antimicrobials. However, little is known about the identity of the signals or conditions sensed by SagS to induce the switch to the sessile, drug tolerant mode of growth. Using a modified Biolog phenotype assay to screen for compounds that modulate attachment in a SagS-dependent manner, we identified glucose-6-phosphate to enhance attachment in a manner dependent on the glucose-6-phosphate concentration and SagS. The stimulatory effect was not limited to the attachment as glucose-6-phosphate likewise enhanced biofilm formation. We show that exposure to glucose-6-phosphate results in decreased swarming motility but increased cellular c-di-GMP levels in biofilms. Genetic analysis indicated that the diguanylate cyclase NicD is an activator of biofilm formation and is not only required for enhanced biofilm formation in response to glucose-6-phosphate but also interacts with SagS. Our findings indicate glucose-6-phosphate to likely mimic a signal or conditions sensed by SagS to activate its motile-sessile switch function. Additionally, our findings provide new insight into the interfaces between the ligand-mediated TCS signaling pathway and c-di-GMP levels.</p>

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Adequate connexin-mediated coupling is required for proper insulin production.

The Journal of Cell Biology ◽

10.1083/jcb.131.6.1561 ◽

1995 ◽

Vol 131 (6) ◽

pp. 1561-1572 ◽

Cited By ~ 90

Author(s):

C Vozzi ◽

S Ullrich ◽

A Charollais ◽

J Philippe ◽

L Orci ◽

...

Keyword(s):

Insulin Secretion ◽

Gap Junctions ◽

Beta Cells ◽

Stable Transfection ◽

Insulin Production ◽

Wild Type ◽

Transfected Cells ◽

Insulin Producing Cells ◽

And Storage ◽

Rat Insulinoma

To assess whether connexin (Cx) expression contributes to insulin secretion, we have investigated normal and tumoral insulin-producing cells for connexins, gap junctions, and coupling. We have found that the glucose-sensitive cells of pancreatic islets and of a rat insulinoma are functionally coupled by gap junctions made of Cx43. In contrast, cells of several lines secreting insulin abnormally do not express Cx43, gap junctions, and coupling. After correction of these defects by stable transfection of Cx43 cDNA, cells expressing modest levels of Cx43 and coupling, as observed in native beta-cells, showed an expression of the insulin gene and an insulin content that were markedly elevated, compared with those observed in both wild-type (uncoupled) cells and in transfected cells overexpressing Cx43. These findings indicate that adequate levels of Cx-mediated coupling are required for proper insulin production and storage.

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New insight into the taxonomic resolution of the genus Bythotrephes Leydig (Crustacea: Cladocera) based on molecular data from Central Europe

Scientific Reports ◽

10.1038/s41598-021-02648-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maciej Karpowicz ◽

Magdalena Świsłocka ◽

Joanna Moroz ◽

Łukasz Sługocki

Keyword(s):

Genetic Analysis ◽

Central Europe ◽

Taxonomic Status ◽

Molecular Data ◽

Coi Gene ◽

Taxonomic Resolution ◽

Monotypic Genus ◽

Mtdna Coi ◽

Xix Century ◽

Insight Into

AbstractThe taxonomic status of the genus Bythotrephes Leydig (Crustacea: Cladocera) has been debated since the second half of the XIX century. The most widespread view of recent decades has been that Bythotrephes is a monotypic genus, which was support by preliminary molecular data. However, the recent detailed morphological revision of this genus clearly distinguishes at least seven species. Therefore, we performed a multi-lake survey in Central Europe to give new insight into the taxonomic status of Bythotrephes by combining genetic analysis with traditional morphology-based taxonomy. Based on the morphology we identified two species in Central Europe, B. brevimanus and B. lilljeborgi, as well as hybrid forms. For the genetic analysis, we used newly obtained 113 sequences of mtDNA COI gene of the 535-bp length Bythotrephes from Central Europe and sequences downloaded from GenBank. There were no significant differences between all analyzed sequences, which supports the hypothesis that Bythotrephes is a monotypic genus, with only one highly polymorphic species. On the other hand, the results of our work could point out that the COI gene is insufficient to evaluate the taxonomic status of Bythotrephes. Nonetheless, we have identified 29 new haplotypes of mtDNA COI, and one which was the same as the haplotype found in North America and Finland. Furthermore, this haplotype was the source variant from which most other haplotypes were derived.

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The Drosophila HNF4 nuclear receptor promotes glucose-stimulated insulin secretion and mitochondrial function in adults

eLife ◽

10.7554/elife.11183 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 38

Author(s):

William E Barry ◽

Carl S Thummel

Keyword(s):

Insulin Secretion ◽

Nuclear Receptor ◽

Transition To Adulthood ◽

Glucose Homeostasis ◽

Mitochondrial Function ◽

Fat Body ◽

Insulin Producing Cells ◽

Glucose Stimulated Insulin Secretion ◽

Developmental Reprogramming ◽

Developmental Switch

Although mutations in HNF4A were identified as the cause of Maturity Onset Diabetes of the Young 1 (MODY1) two decades ago, the mechanisms by which this nuclear receptor regulates glucose homeostasis remain unclear. Here we report that loss of Drosophila HNF4 recapitulates hallmark symptoms of MODY1, including adult-onset hyperglycemia, glucose intolerance and impaired glucose-stimulated insulin secretion (GSIS). These defects are linked to a role for dHNF4 in promoting mitochondrial function as well as the expression of Hex-C, a homolog of the MODY2 gene Glucokinase. dHNF4 is required in the fat body and insulin-producing cells to maintain glucose homeostasis by supporting a developmental switch toward oxidative phosphorylation and GSIS at the transition to adulthood. These findings establish an animal model for MODY1 and define a developmental reprogramming of metabolism to support the energetic needs of the mature animal.

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Mythimna separata herbivory primes maize resistance in systemic leaves

Journal of Experimental Botany ◽

10.1093/jxb/erab083 ◽

2021 ◽

Author(s):

Saif ul Malook ◽

Yuxing Xu ◽

Jinfeng Qi ◽

Jing Li ◽

Lei Wang ◽

...

Keyword(s):

Genetic Analysis ◽

Jasmonic Acid ◽

Insect Feeding ◽

Mythimna Separata ◽

Simulated Herbivory ◽

Down Regulation ◽

Number Of Genes ◽

Metabolite Quantification ◽

Maize Resistance ◽

Insight Into

Abstract Biotic and abiotic cues can trigger priming in plants, which enables plants to respond to subsequent challenge with stronger and/or faster responses. It is well known that herbivory activates defense-related responses in systemic leaves. However, little is known about whether insect feeding activates priming in systemic leaves. To determine whether and how herbivory induces priming in maize systemic leaves, a combination of insect bioassays, phytohormone and defense metabolite quantification, and genetic and transcriptome analyses were performed. Actual and simulated Mythimna separata herbivory in maize local leaves primed the systemic leaves for enhanced accumulation of jasmonic acid and benzoxazinoids and increased resistance to M. separata. Activation of priming in maize systemic leaves depends on both the duration of simulated herbivory and perception of M. separata oral secretions in the local leaves, and genetic analysis indicated that jasmonic acid and benzoxazinoids mediate the primed defenses in systemic leaves. Consistently, in response to simulated herbivory, the primed systemic leaves exhibited a large number of genes that were uniquely regulated or showed further up- or down-regulation compared with the non-primed systemic leaves. This study provides new insight into the regulation and ecological function of priming in maize.

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Complete Genetic Analysis of Plasmids Carried by Two Nonclonal bla NDM-5 - and mcr-1 -Bearing Escherichia coli Strains: Insight into Plasmid Transmission among Foodborne Bacteria

Microbiology Spectrum ◽

10.1128/spectrum.00217-21 ◽

2021 ◽

Author(s):

Xiaobo Liu ◽

Ruichao Li ◽

Ning Dong ◽

Lianwei Ye ◽

Edward Wai-Chi Chan ◽

...

Keyword(s):

Escherichia Coli ◽

Genetic Analysis ◽

Bacterial Pathogens ◽

Multidrug Resistant ◽

Content Type ◽

Foodborne Bacteria ◽

Clinical Pathogens ◽

Insight Into

Carbapenem and colistin are last-resort antibiotics used to treat serious clinical infections caused by multidrug-resistant (MDR) bacterial pathogens. Plasmids encoding resistance to carbapenems and colistin have been reported in clinical pathogens in recent years, and yet few studies reported cocarriage of mcr and bla NDM genes in Escherichia coli strains of food origin.

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Targeted Lipidomics Reveals Associations Between Serum Sphingolipids and Insulin Sensitivity Measured by the Hyperinsulinemic-euglycemic Clamp

10.21203/rs.3.rs-97467/v1 ◽

2020 ◽

Author(s):

Jingya Ye ◽

Xuan Ye ◽

Wanzi Jiang ◽

Chenyan Lu ◽

Xiaomei Geng ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Metabolic Diseases ◽

Roc Curves ◽

Diagnostic Value ◽

Ionization Mass ◽

Euglycemic Clamp ◽

Hyperinsulinemic Euglycemic Clamp ◽

Obesity And Diabetes ◽

Insight Into

Abstract BackgroundSPs are a group of ubiquitously produced lipids that are structurally involved in cell membranes and include SMs, ceramides, GM3s, etc. Sphingolipids and their substrates and constituents, FAs, are implicated in the pathogenesis of various metabolic diseases associated with obesity, diabetes, and atherosclerosis. Decreased insulin sensitivity or insulin secretion is a multifactorial condition related to obesity and diabetes. Therefore, it is likely that perturbations in serum SPs are associated with diseases. Identifying these associations may reveal useful predictors or give perceptive insight into disease processes. This study aimed to systematically investigate the associations between serum sphingolipids and insulin sensitivity as well as insulin secretion. This study also aimed to reveal potential predictors for insulin sensitivity or give perceptive insight into disease processes.MethodsWe conducted a lipidomics evaluation of molecularly distinct SPs in the serum of 86 consecutive Chinese adults with or without obesity and diabetes using electrospray ionization mass spectrometry coupled with liquid chromatography. The GIR30 was measured under steady conditions to assess insulin sensitivity by the gold standard hyperinsulinemic-euglycemic clamp, and FPIR was measured to evaluate insulin secretion by the IVGTT. We created the ROC curves to detect the serum SMs diagnostic value and establish the diagnosis of insulin sensitivity based on GIR30 derived from the glucose clamp, which is the standard method, and the cutoff point of GIR30 was set as 5.1 mg/(kg *min).ResultsDifferential correlation network analysis illustrated correlations amongst lipids, insulin sensitivity, insulin secretion and other clinical indexes. Total and subspecies of serum SMs and globotriaosylceramides (Gb3s) were positively related to GIR30, free FAs (FFA 16:1, FFA20:4), some long chain GM3 and complex ceramide GluCers showed strong negative correlations with GIR30. We also found that higher concentrations of serum free FAs (FFA 22:6, FFA 22:5, FFA 18:2, FFA 18:1) were associated with a higher risk of decreased insulin secretion. Notably, ROC curves showed that SM/Cer and SM d18:0/26:0 may be good serum lipid predictors of diagnostic indicators of insulin sensitivity close to conventional clinical indexes such as 1/HOMA-IR (all areas under the curve >0.80) based on GIR30 as standard diagnostic criteria. ConclusionsThese results provide novel associations between serum sphingolipid between insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. This suggests that the balance of SMs metabolism, rather than ceramide is correlated with the pathology of insulin resistance, obesity and T2DM. We further identify two specific SPs that may represent prognostic biomarkers for insulin sensitivity.

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Insect embryogenesis – what is ancestral and what is derived?

Development ◽

10.1242/dev.1994.supplement.193 ◽

1994 ◽

Vol 1994 (Supplement) ◽

pp. 193-199

Author(s):

Diethard Tautz ◽

Markus Friedrich ◽

Reinhard Schröder

Keyword(s):

Pattern Formation ◽

Genetic Analysis ◽

Early Development ◽

Molecular Mechanisms ◽

Early Embryogenesis ◽

Molecular Pathways ◽

Deep Insight ◽

Insect Embryogenesis ◽

Definitive Answer ◽

Insight Into

The systematic genetic analysis of Drosophila development has provided us with a deep insight into the molecular pathways of early embryogenesis. The question arises now whether these insights can serve as a more general paradigm of early development, or whether they apply only to advanced insect orders. Though it is too early to give a definitive answer to this question, we suggest that there is currently no firm reason to believe that the molecular mechanisms that were elucidated in Drosophila may not also apply to other forms of insect embryogenesis. Thus, many of the Drosophila genes involved in early pattern formation may have comparable functions in other insects and possibly throughout the arthropods.

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Dysregulated lncRNAs Regulate Human Umbilical Cord Mesenchymal Stem Cells Differentiation into Insulin-Producing Cells by Forming a Regulatory Network with mRNAs

10.21203/rs.3.rs-1073927/v1 ◽

2021 ◽

Author(s):

Tianqin Xie ◽

Qiming Huang ◽

Qiulang Huang ◽

Haixia Zeng ◽

Jianping Liu

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Insulin Secretion ◽

Signaling Pathway ◽

Beta Cells ◽

Umbilical Cord ◽

Pancreatic Beta Cells ◽

Differentially Expressed ◽

Human Umbilical Cord ◽

Insulin Producing Cells

Abstract ObjectiveIn recent years, cell therapy has become a new research direction in the treatment of diabetes. However, the underlying molecular mechanisms of mesenchymal stem cells (MSCs) participate in such treatment has not been clarified. MethodsIn this study, human umbilical cord mesenchymal stem cells (HUC-MSCs) isolated from newborns were progressively induced into insulin-producing cells (IPCs) using small molecules. HUC-MSCs (S0) and four induced stage (S1-S4) samples were prepared. We then performed transcriptome sequencing experiments to obtain the dynamic expression profiles of both mRNAs and long noncoding RNAs (lncRNAs). ResultsWe found that the number of differentially expressed lncRNAs and mRNAs showed a decreasing trend during differentiation. Gene Ontology (GO) analysis showed that the target genes of differentially expressed lncRNAs were associated with translation, cell adhesion, and cell connection. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the NF-KB signaling pathway, MAPK signaling pathway, HIPPO signaling pathway, PI3K-Akt signaling pathway, and p53 signaling pathway were enriched in these differentially expressed lncRNA-targeting genes. We also found that the coexpression of the lncRNA: CTBP1-AS2 with the PROX1, and the lncRNAs AC009014.3 and GS1-72M22.1 with the mRNA JARID2 was related to the development of pancreatic beta cells. Moreover, the coexpression of the lncRNAs :XLOC_ 050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14- AS1, RP11-148K1.12, and CTD2020K17.3 with p53, regulated insulin secretion by pancreatic beta cells.ConclusionThis research revealed that HUC-MSCs combined with small molecule compounds were successfully induced into IPCs. Differentially expressed lncRNAs may regulate the insulin secretion of pancreatic beta cells by regulating multiple signaling pathways. The lncRNAs: AC009014.3,Gs1-72m21.1 and CTBP1-AS2 may be involved in the development of pancreatic beta cells, and the lncRNAs: XLOC_050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14-AS1, RP11-148K1.12, and CTD2020K17.3 may be involved in regulating the insulin secretion of pancreatic beta cells, thus providing a lncRNA catalog for future research regarding the mechanism of the transdifferentiation of HUC-MSCs into IPCs. It also provides a new theoretical basis for the transplantation of insulin-producing cells into diabetic patients in the future.

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