Molecular characterization of insulin-like peptides in the yellow fever mosquito, Aedes aegypti: Expression, cellular localization, and phylogeny

Riehle, Michael A.; Fan, Yongliang; Cao, Chun; Brown, Mark R.

doi:10.1016/j.peptides.2006.07.016

Cited by 109 publications

(167 citation statements)

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“…Each A. aegypti ILP exhibits intron/exon organization similar to other insulin superfamily members (15). Each A. aegypti ILP propeptide with the possible exception of ILP6 also contains sites flanking the C chain, suggesting insulin/relaxin-like processing (15), whereas cysteine spacing patterns suggested conservation in disulfide bridge formation with mammalian ILPs (Fig. 1).…”

Section: Resultsmentioning

confidence: 93%

“…IGFs form the same disulfide bridges but remain single peptides at maturity because their C chain is not cleaved, whereas relaxins are processed like insulin but exhibit differences in primary structure that include the presence of basic lysine and/or arginine residues flanking the first cysteine of the B chain (5,19). Each A. aegypti ILP exhibits intron/exon organization similar to other insulin superfamily members (15). Each A. aegypti ILP propeptide with the possible exception of ILP6 also contains sites flanking the C chain, suggesting insulin/relaxin-like processing (15), whereas cysteine spacing patterns suggested conservation in disulfide bridge formation with mammalian ILPs (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Prior studies indicated that mosquito brain extracts and bovine insulin each stimulate ecdysteroid production by the ovaries (14). A. aegypti also encodes eight predicted ILP family members of which three (ILP1, ILP3 and ILP8) are specifically expressed in brains of adult females (15). Combined with the finding that ovaries express IR [mosquito IR (MIR)] and AKT (16)(17)(18) homologs, these results suggest an endogenous ILP of brain origin stimulates egg maturation by activating the insulin signaling pathway in the ovaries.…”

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confidence: 99%

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An insulin-like peptide regulates egg maturation and metabolism in the mosquito Aedes aegypti

Brown¹,

Clark²,

Gulia³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Ingestion of vertebrate blood is essential for egg maturation and transmission of disease-causing parasites by female mosquitoes. Prior studies with the yellow fever mosquito, Aedes aegypti, indicated blood feeding stimulates egg production by triggering the release of hormones from medial neurosecretory cells in the mosquito brain. The ability of bovine insulin to stimulate a similar response further suggested this trigger is an endogenous insulin-like peptide (ILP). A. aegypti encodes eight predicted ILPs. Here, we report that synthetic ILP3 dose-dependently stimulated yolk uptake by oocytes and ecdysteroid production by the ovaries at lower concentrations than bovine insulin. ILP3 also exhibited metabolic activity by elevating carbohydrate and lipid storage. Binding studies using ovary membranes indicated that ILP3 had an IC 50 value of 5.9 nM that was poorly competed by bovine insulin. Autoradiography and immunoblotting studies suggested that ILP3 binds the mosquito insulin receptor (MIR), whereas loss-of-function experiments showed that ILP3 activity requires MIR expression. Overall, our results identify ILP3 as a critical regulator of egg production by A. aegypti.

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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An insulin-like peptide regulates egg maturation and metabolism in the mosquito Aedes aegypti

Brown¹,

Clark²,

Gulia³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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217

281

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“…Individual Dilps are found in different tissues and not all appear to be neurosecretory (Brogiolo et al, 2001). In the African malaria mosquito, Anopheles gambiae, there are five putative insulin-like peptides (Riehle et al, 2002) and in the yellow fever mosquito, Aedes aegypti, there are eight putative insulin-like peptides at least three of which are produced in the brain (Riehle et al, 2006).…”

Section: Insulin-like Proteins In Insectsmentioning

confidence: 99%

Nutritional sensitivity of fifth instar prothoracic glands in the tobacco hornworm, Manduca sexta

Walsh

Smith

2011

Journal of Insect Physiology

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The tobacco hornworm, Manduca sexta, has been a useful model for studying insect endocrinology. In M. sexta the majority of growth occurs during the fifth (final) larval stage. This growth is concurrent with endocrine changes that lead to a metamorphic molt. Past research has focused on the interplay of three growth hormones: juvenile hormone (JH), prothoracicotropic hormone (PTTH) and ecdysone, in regulating metamorphosis. The prothoracic glands, source of ecdysteroid molting hormones in insects, play a crucial role in coordinating growth. Insulin/insulin-like growth factor (IGF) signaling has been shown to regulate growth and secretion of steroidogenic tissues in both vertebrates and invertebrates, but it had yet to be well-characterized in M. sexta.In this dissertation I examined the role of insulin-directed growth in prothoracic glands during both normal larval development and in response to nutrient deprivation. In particular, I predicted that in response to a reduction in nutrients, the prothoracic glands would stop growing and ecdysone secretion would be reduced. Changes were assessed in actin abundance and in two nutritionally sensitive transcripts, insulin receptor and 4EBP.Actin abundance in prothoracic glands increased in the first four days of this stage, demo nstrating significant growth. Actin decreased in glands from starved larvae, indicating a cessation of growth. Both insulin receptor and 4EBP transcript were present during normal larval development. As expected, both insulin receptor and 4EBP transcript increased in response to starvation. This research was the first demonstration of insulin signaling in prothoracic glands of fifth instar M. sexta larvae, and revealed nutritional sensitivity of the prothoracic glands. 5Finally, ecdysone assays were conducted to determine the impact of nutrition on glandular secretory capacity. Starved larvae were unable to secrete as much ecdysone as fed controls. Injections of insulin were unable to rescue the ability of the glands to secrete high levels of ecdysone. This demonstrated that although insulin signaling was correlated with normal growth of the glands, insulin is not sufficient to impact the ability of the glands to secrete ecdysone in the absence of nutrie nts. 6 This thesis is dedicated to my parents,Robert and Angela Walsh, whose love and support made this dissertation possible.

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“…In addition, while insulins are canonical activators of Receptor Tyrosine Kinase (RTK) activity, some ligands in C. elegans may act as antagonists of IIS [reviewed in (20)]. For mosquitoes, eight ILPs have been identified (21) and functional studies indicate roles for different ILPs in egg laying, diapause, immunity, and metabolism (22)(23)(24). The ILPS are thought to be secreted proteins (25,26), as are mammalian insulin and IGFs (2).…”

mentioning

confidence: 99%

Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities

Zhang

Liu

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

170

160

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Insulin/Insulin-like growth factor signaling regulates homeostasis and growth in mammals, and is implicated in diseases from diabetes to cancer. In Drosophila melanogaster, as in other invertebrates, multiple Insulin-Like Peptides (DILPs) are encoded by a family of related genes. To assess DILPs' physiological roles, we generated small deficiencies that uncover single or multiple dilps, generating genetic loss-of-function mutations. Deletion of dilps1-5 generated homozygotes that are small, severely growth-delayed, and poorly viable and fertile. These animals display reduced metabolic activity, decreased triglyceride levels and prematurely activate autophagy, indicative of ''starvation in the midst of plenty,'' a hallmark of Type I diabetes. Furthermore, circulating sugar levels are elevated in Df [dilp1-5] homozygotes during eating and fasting. In contrast, Df[dilp6] or Df[dilp7] animals showed no major metabolic defects. We discuss physiological differences between mammals and insects that may explain the unexpected survival of lean, 'diabetic' flies.diabetes ͉ DILP ͉ Drosophila insulin receptor ͉ insect physiology ͉ trehalose

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Molecular characterization of insulin-like peptides in the yellow fever mosquito, Aedes aegypti: Expression, cellular localization, and phylogeny

Cited by 109 publications

References 55 publications

An insulin-like peptide regulates egg maturation and metabolism in the mosquito Aedes aegypti

An insulin-like peptide regulates egg maturation and metabolism in the mosquito Aedes aegypti

Nutritional sensitivity of fifth instar prothoracic glands in the tobacco hornworm, Manduca sexta

Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities

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