ins-18;ins-7

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Genetic mutants with ins-18, ins-7 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
25
Diet
NGM
Lifespan (days)
13.54
Lifespan change (compared to wild type)
15.04%
Phenotype
We measured the adult lifespan of ins-18(tm339) animals under an ins-7(tm1907) background, which provides a lifespan-extending condition. ins-7 is one of the insulin-like genes and its RNAi knockdown has been reported to induce an extended adult lifespan. As expected, the mean lifespan of ins-7(tm1907) animals was extended by 4.8 days. In contrast, the mean lifespan of ins-18;ins-7 double mutant animals was 2.7 days shorter than that for ins-7 animals.
Lifespan comparisons
Double mutant ins-18(tm339);ins-7(tm1907) has a lifespan of 13.54 days, while single mutant ins-18(tm339) has a lifespan of 11.77 days, single mutant ins-7(tm1907) has a lifespan of 16.66 days and wild type has a lifespan of 11.77 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Matsunaga Y et al., 2012, Physiological function, expression pattern, and transcriptional regulation of a Caenorhabditis elegans insulin-like peptide, INS-18. Biochem Biophys Res Commun. 423(3):478-83 22683638 Click here to select all mutants from this PubMed ID in the graph
Abstract
In Caenorhabditis elegans, insulin/insulin-like growth factor (IGF)-1 signaling (IIS) is an important pathway that controls larval diapause and adult lifespan. The IIS pathway is modulated by many insulin-like peptides (ILPs) through the DAF-2 receptor, the sole insulin/IGF-1 receptor-like protein in C. elegans. We previously identified the ILP, INS-18, and predicted its tertiary structure to be similar to the crystal structures of human insulin and IGF-1. In this study, the physiological function of INS-18 was first examined by gene disruption and overexpression, and we identified INS-18 as a DAF-2 antagonist required for larval diapause and longevity. Analysis of the INS-18 expression pattern using a reporter gene showed it to be expressed in nerve cells, including hermaphrodite-specific neurons (HSNs) at the adult stage. Other ILP expressions have not been previously observed in HSNs, and we believe that INS-18 expression in these cells may contribute to longevity by regulating reproduction. Loss of the DAF-16 transcription factor located downstream of the IIS pathway completely blocked ins-18 expression. We propose a positive feedback model for the regulation of ins-18 expression in which an antagonist binding to the DAF-2 receptor increases ins-18 gene expression, thus leading to increased INS-18 protein levels and increased DAF-2 receptor binding. Thus, this study provides a new insight into the hormonal regulation of insulin, an important and widespread process in the animal kingdom.

Search genes: ins-18 ins-7

Entrez ID
Symbol
GenAge
Wormbase ID

172600
ins-18
View on GenAge (ins-18)
WBGene00002101

INSulin related

Locus: CELE_T28B8.2

Wormbase description: ins-18 encodes one of 40 C. elegans insulin/IGF-like peptides; INS-18, along with INS-1, are the only two C. elegans insulins that contain a C peptide, characteristic of mammalian insulins, connecting the B and A chains; overexpression of ins-18 induces dauer arrest at 26 degrees C and enhances the dauer arrest seen in a daf-2 mutant at 20 degrees C, suggesting that INS-18 functions to antagonize DAF-2 receptor signaling; in addition, daf-7; ins-18 doubly mutant animals show dauer maintenance defects, suggesting that INS-18 activity is required to properly maintain the dauer developmental state; ins-18::gfp reporters are expressed in neurons and the intestine.

Entrez ID
Symbol
GenAge
Wormbase ID

191688
ins-7
View on GenAge (ins-7)
WBGene00002090

INSulin related;Probable insulin-like peptide beta-type 4

Locus: CELE_ZK1251.2

Wormbase description: ins-7 encodes an insulin/IGF-1-like peptide; INS-7 is one of 40 insulin-like peptides in C. elegans; INS-7 likely functions as an agonist for the DAF-2 insulin/IGF-1 receptor, as loss of ins-7 activity via RNAi results in: 1) a significantly increased lifespan that is not further extended in long-lived daf-2 mutant animals, and 2) an increased frequency of dauer formation in animals containing an incompletely penetrant daf-2 mutation; an ins-7 promoter fusion is expressed in amphid sensory neurons, labial neurons, the nerve ring, and ventral cord and tail neurons; ins-7 expression is positively regulated by DAF-2-mediated insulin signaling, suggesting that a positive feedback loop involving INS-7 may amplify DAF-2 pathway activity.

Orthologs of ins-18;ins-7 in SynergyAge

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Orthologs of ins-18 in SynergyAge

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Orthologs of ins-7 in SynergyAge

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Species	Gene