Diverse functions of insulin-like 3 peptide

Esteban‐Lopez, Maria; Agoulnik, Alexander I.

doi:10.1530/joe-20-0168

Cited by 26 publications

(20 citation statements)

References 78 publications

(141 reference statements)

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“…Insulin-like peptide 3 (INSL3) is a member of the insulin/relaxin superfamily and classically described as a Leydig and ovarian theca cell-derived protein and critical regulator of male and female reproductive physiology [99]. However, INSL3 is also shown to regulate normal bone and skeletal muscle physiology, including appropriate bone mineralization [100], as well as promotion of skeletal muscle protein synthesis through the Akt/mTOR/S6 pathway [101].…”

Section: Insl3mentioning

confidence: 99%

Neural Mechanisms of Cancer Cachexia

Olson

Diba

Korzun

et al. 2021

Cancers

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Nearly half of cancer patients suffer from cachexia, a metabolic syndrome characterized by progressive atrophy of fat and lean body mass. This state of excess catabolism decreases quality of life, ability to tolerate treatment and eventual survival, yet no effective therapies exist. Although the central nervous system (CNS) orchestrates several manifestations of cachexia, the precise mechanisms of neural dysfunction during cachexia are still being unveiled. Herein, we summarize the cellular and molecular mechanisms of CNS dysfunction during cancer cachexia with a focus on inflammatory, autonomic and neuroendocrine processes and end with a discussion of recently identified CNS mediators of cachexia, including GDF15, LCN2 and INSL3.

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Section: Insl3mentioning

confidence: 99%

Neural Mechanisms of Cancer Cachexia

Olson

Diba

Korzun

et al. 2021

Cancers

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“…This scheme raises the question as to how the functions of these two receptors activated by IGF might differ. IGF and the Drosophila irps stimulate growth, the echinoderm GSS stimulates oocyte maturation and ovulation ( Mita et al, 2009 ), relaxin and INSL3 affet various developmental and reproductive processes ( Ivell et al, 2020 ; Esteban-Lopez & Agoulnik, 2020 ), gonadulin is expressed by the gonads as well as the imaginal discs in flies ( Garelli et al, 2012 ; Liao & Nässel, 2020 ; Veenstra, 2020b ; Veenstra et al, 2021 ), and dilp7 is expressed in a sex specific manner ( Miguel-Aliaga, Thor & Gould, 2008 ; Yang et al, 2008 ; Castellanos, Tang & Allan, 2013 ). These hormones stimulate growth, development and reproduction, processes that are intimately linked; without growth and development reproduction is impossible and growth without reproduction is useless in sexually reproducing species.…”

Section: Discussionmentioning

confidence: 99%

Ambulacrarian insulin-related peptides and their putative receptors suggest how insulin and similar peptides may have evolved from insulin-like growth factor

Veenstra

2021

PeerJ

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Background Some insulin/IGF-related peptides (irps) stimulate a receptor tyrosine kinase (RTK) that transfers the extracellular hormonal signal into an intracellular response. Other irps, such as relaxin, do not use an RTK, but a G-protein coupled receptor (GPCR). This is unusual since evolutionarily related hormones typically either use the same or paralogous receptors. In arthropods three different irps, i.e. arthropod IGF, gonadulin and Drosophila insulin-like peptide 7 (dilp7), likely evolved from a gene triplication, as in several species genes encoding these three peptides are located next to one another on the same chromosomal fragment. These arthropod irps have homologs in vertebrates, suggesting that the initial gene triplication was perhaps already present in the last common ancestor of deuterostomes and protostomes. It would be interesting to know whether this is indeed so and how insulin might be related to this trio of irps. Methodology Genes encoding irps as well as their putative receptors were identified in genomes and transcriptomes from echinoderms and hemichordates. Results A similar triplet of genes coding for irps also occurs in some ambulacrarians. Two of these are orthologs of arthropod IGF and dilp7 and the third is likely a gonadulin ortholog. In echinoderms, two novel irps emerged, gonad stimulating substance (GSS) and multinsulin, likely from gene duplications of the IGF and dilp7-like genes respectively. The structures of GSS diverged considerably from IGF, which would suggest they use different receptors from IGF, but no novel irp receptors evolved. If IGF and GSS use different receptors, and the evolution of GSS from a gene duplication of IGF is not associated with the appearance of a novel receptor, while irps are known to use two different types of receptors, the ancestor of GSS and IGF might have acted on both types of receptors while one or both of its descendants act on only one. There are three ambulacrarian GPCRs that have amino acid sequences suggestive of being irp GPCRs, two of these are orthologs of the gonadulin and dilp7 receptors. This suggests that the third might be an IGF receptor, and that by deduction, GSS only acts on the RTK. The evolution of GSS from IGF may represent a pattern, where IGF gene duplications lead to novel genes coding for shorter peptides that activate an RTK. It is likely this is how insulin and the insect neuroendocrine irps evolved independently from IGF. Conclusion The local gene triplication described from arthropods that yielded three genes encoding irps was already present in the last common ancestor of protostomes and deuterostomes. It seems plausible that irps, such as those produced by neuroendocrine cells in the brain of insects and echinoderm GSS evolved independently from IGF and, thus, are not true orthologs, but the result of convergent evolution.

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“…This scheme raises the question as to how the functions of these two receptors activated by IGF might differ. IGF and the drosophila irps stimulate growth, the echinoderm GSS stimulates oocyte maturation and ovulation (Mita et al, 2009), relaxin and INSL3 affet various developmental and reproductive processes (Ivell et al, 2020; Esteban-Lopez & Agoulnik, 2020), gonadulin is expressed by the gonads as well as the imaginal in flies (Garelli et al, 2012; Liao & Nässel, 2020; Veenstra, 2020b; Veenstra et al, 2021) and dilp7 is expressed in a sex specific manner (Miguel-Aliaga, Thor & Gould, 2008; Yang et al, 2008; Castellanos, Tang & Allan, 2013). These hormones stimulate growth, development and reproduction, processes that are intimately linked; without growth and development reproduction is impossible and growth without reproduction is useless in sexually reproducing species.…”

Section: Discussionmentioning

confidence: 99%

Ambulacrarian insulin-related peptides and their putative receptors suggest how insulin and similar peptides may have evolved from Insulin-like Growth Factor

Veenstra

2021

Preprint

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Background: Insulin is evolutionarily related to the insulin-like growth factors (IGFs) and like the latter stimulates a receptor tyrosine kinase (RTK) that transfers the extracellular hormonal signal into an intracellular response. Other hormones related to insulin, such as relaxin, do not use an RTK, but a G-protein coupled receptor (GPCR). This is unusual since evolutionarily related hormones typically either use the same or paralogous receptors. In arthropods three different IGF-related peptides likely evolved from a gene triplication, as in several species genes coding these three peptides are located next to one another on the same chromosomal fragment. Of these three hormones one, an IGF-like hormone, acts through an RTK, while the other two use a GPCR. This suggests that the ancestral IGF-like peptide may have used both types of receptors. These arthropod insulin-like peptides have homologs in vertebrates, which suggests that the initial gene triplication was perhaps already present in the last common ancestor of deuterostomes and protostomes. It would be interesting to know whether this is indeed so and to establish how insulin and other insulin-like peptides might be related to this trio of IGF-related hormones. Methodology: Genes coding insulin and related peptides as well as their putative receptors were identified in genomes and transcriptomes from echinoderms and hemichordates. Results: A similar triplet of genes coding insulin-like peptides is also found in some hemichordates and echinoderms. Two of the three ambulacrarian peptides are orthologs of arthropod IGF and Drosophila insulin-like peptide 7 (dilp7), while the third one looks like an ortholog of the arthropod peptide gonadulin. In echinoderms two novel insulin-like peptides emerged, gonad stimulating substance (GSS) and multinsulin, likely from gene duplications of the IGF and dilp7-like genes respectively. However, no novel receptors for insulin-like peptides evolved. If IGF were to act through both a GPCR and an RTK it would suggest that GSS acts on only one of the two receptors, possibly the RTK. The evolution of GSS from IGF may represent a pattern, where IGF gene duplications lead to novel genes coding shorter peptides that have lost their ability to activate a GPCR. It is likely this is how insulin and the insect neuroendocrine insulin-like peptides evolved independently from IGF. Conclusion: The local gene triplication previously described from arthropods that yielded three genes coding IGF-related peptides was already present in the last common ancestor of protostomes and deuterostomes. It seems plausible that insulin and other insulin-like peptides, such as those produced by neuroendocrine cells in the brain of insects and echinoderm GSS evolved independently from IGF and thus are not true orthologs, but the result of convergent evolution.

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Diverse functions of insulin-like 3 peptide

Cited by 26 publications

References 78 publications

Neural Mechanisms of Cancer Cachexia

Neural Mechanisms of Cancer Cachexia

Ambulacrarian insulin-related peptides and their putative receptors suggest how insulin and similar peptides may have evolved from insulin-like growth factor

Ambulacrarian insulin-related peptides and their putative receptors suggest how insulin and similar peptides may have evolved from Insulin-like Growth Factor

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