Insulin signaling in the fruit fly,

Insulin signaling in the fruit fly, D. melanogaster
Similar mechanisms and functions of insulin peptides have
been observed in another invertebrate model organism,
D. melanogaster. Genome analysis has revealed eight
putative Drosophila insulin-like peptide (dILP) precursors
with structure similar to mammalian insulin (Brogiolo et al.
2001; Colombani et al. 2012). These eight genes are found
on two chromosomes as shown in Fig. 2a. dILPs 1-5 are
found on the third chromosome as a gene cluster, dILP-8 is
on the third chromosome at a separate locus while dILP 6
and 7 are on the X-chromosome as separate loci (Brogiolo
et al. 2001; Colombani et al. 2012). Orthologs to the
mammalian and C. elegans insulin pathway have also been
identified including a dInR (Drosophila insulin receptor),
chico and lnk (IRS), PI3K and akt (Protein kinase B)
(Staveley et al. 1998; Leevers et al. 1996; Poltilove et al.
2000; Werz et al. 2009). Complex expression of dILPs in
D. melanogaster is spatially and temporally regulated. In
relation to modulating neural function and behaviors, the
median neurosecretory cells in the fly brain express a
subset of dILPs (Brogiolo et al. 2001; Rulifson et al. 2002).
Ablation of insulin producing cells results in growth
defects and misregulated carbohydrate concentration in the
hemolymph (Rulifson et al. 2002).
Similar to results obtained using the C. elegans model,
insulin signaling in D. melanogaster has also been shown to
regulate multiple aspects of neuronal development. During
development, a small cluster of median neurosecretory cells
release insulin into the circulatory system in response to
nutrients (Ikeya et al. 2002). Circulating insulin acts on
neurons in the mushroom body and regulates the feeding
behavior and growth of the fly larvae (Zhao and Campos
2012). In this context, the source and identity of dILPs
acting on the mushroom body remains unclear. dILPs also
play an important role in the dynamic regulation of stem
cell growth in response to metabolic changes. During
development, quiescent neural stem cells in the brain must
be reactivated for proliferation to generate adult neurons.
Nutritional status is sensed by glial cells that express and
secrete dILPs. Locally secreted dILP2 and dILP6 from glia
reactivates neural stem cells by acting on the PI3K/Akt
pathway (Cheetham and Brand 2013). In summary, these
studies demonstrate the role of dILPs in coupling nutritional
status to neural development and growth.
Insulins have also been shown to couple environmental
conditions to physiology in the adult fly. D. melanogaster
S6 kinase is involved in modulating hunger response by
regulating the opposing effects of insulin and neuropeptide
F signaling pathways (Wu et al. 2005). Low levels of circulating
insulin leads to the increase in the expression
levels of the short neuropeptide F receptor at the synapse
between the olfactory receptor neuron and the projection
neuron. This transcription-dependent event, which is
inhibited by insulin signaling, enhances the attraction of
adult flies to food (Root et al. 2011). These results show
that dILPs produced in the brain couple nutritional status with neural circuit functions. In contrast to C. elegans
findings of fast transcription-independent action of ILPs,
the timescale of insulin action in flies can range from hours
to days to accommodate changing nutrient availability. Not
surprisingly, many of these dILP actions require dFOXO
and transcription. To summarize, these studies show that
regardless of location and timescale, insulin represents a
versatile signal that works with other peptide signaling
systems to integrate nutritional status to regulate neuronal
development and function.
In some cases, dILP signaling outside of the nervous
system does not involve dFOXO. Mutations in dFOXO do
not abrogate the increase in oxidative stress resistance upon
exposure to paraquat seen in animals with reduced insulin
signaling (Slack et al. 2011; Broughton et al. 2005), suggesting
a transcription-independent role for insulin.
Moreover, dFOXO does not seem to be required to promote
fecundity, which in turn is influenced by insulin
signaling (Slack et al. 2011). Together, studies of longevity
phenotypes provide support that insulin signaling uses
diverse downstream mechanisms for regulating somatic
changes. Molecular machinery other than dFOXO can also
mediate somatic changes when insulin signaling is
involved.

Hasil (Bahasa Indonesia) 1:

Insulin signaling di lalat buah, D. melanogasterMekanisme dan fungsi insulin peptida yang serupa telahtelah diamati pada organisme invertebrata model lain,D. melanogaster. Analisis genom telah mengungkapkan delapandiduga Drosophila prekursor insulin-seperti peptida (dILP)dengan struktur mirip dengan mamalia insulin (Brogiolo et al.tahun 2001; Colombani et al. 2012). Gen ini delapan ditemukanpada dua kromosom seperti ditunjukkan pada gambar 2a. dILPs 1-5 adalahditemukan pada kromosom ketiga sebagai sebuah cluster gen, adalah dILP-8dalam kromosom ketiga di lokus terpisah sambil dILP 6dan 7 x-kromosom sebagai lokus terpisah (Brogioloet al. 2001; Colombani et al. 2012). Orthologs untukMamalia dan C. elegans insulin jalur juga telahdiidentifikasi termasuk dInR (Drosophila reseptor insulin),Chico dan lnk (IRS), PI3K dan akt (Protein kinase B)(Staveley et al. 1998; Leevers et al, 1996; Poltilove et al.2000; Werz et al., 2009). Kompleks ekspresi dILPs diD. melanogaster spasial dan temporal diatur. Dalamhubungan dengan modulasi fungsi saraf dan perilaku,rata-rata neurosecretory sel dalam otak terbang Checksubset dari dILPs (Brogiolo et al. 2001; Rulifson et al. 2002).Ablasi insulin memproduksi sel hasil dalam pertumbuhanCacat dan karbohidrat misregulated konsentrasi dalamhemolymph (Rulifson et al. 2002).Mirip dengan hasil yang diperoleh dengan menggunakan model C. elegans,insulin signaling pada D. melanogaster juga telah ditunjukkan untukregulate multiple aspects of neuronal development. Duringdevelopment, a small cluster of median neurosecretory cellsrelease insulin into the circulatory system in response tonutrients (Ikeya et al. 2002). Circulating insulin acts onneurons in the mushroom body and regulates the feedingbehavior and growth of the fly larvae (Zhao and Campos2012). In this context, the source and identity of dILPsacting on the mushroom body remains unclear. dILPs alsoplay an important role in the dynamic regulation of stemcell growth in response to metabolic changes. Duringdevelopment, quiescent neural stem cells in the brain mustbe reactivated for proliferation to generate adult neurons.Nutritional status is sensed by glial cells that express andsecrete dILPs. Locally secreted dILP2 and dILP6 from gliareactivates neural stem cells by acting on the PI3K/Aktpathway (Cheetham and Brand 2013). In summary, thesestudies demonstrate the role of dILPs in coupling nutritionalstatus to neural development and growth.Insulins have also been shown to couple environmentalconditions to physiology in the adult fly. D. melanogasterS6 kinase is involved in modulating hunger response byregulating the opposing effects of insulin and neuropeptideF signaling pathways (Wu et al. 2005). Low levels of circulatinginsulin leads to the increase in the expressionlevels of the short neuropeptide F receptor at the synapsebetween the olfactory receptor neuron and the projectionneuron. This transcription-dependent event, which isinhibited by insulin signaling, enhances the attraction ofadult flies to food (Root et al. 2011). These results showthat dILPs produced in the brain couple nutritional status with neural circuit functions. In contrast to C. elegansfindings of fast transcription-independent action of ILPs,the timescale of insulin action in flies can range from hoursto days to accommodate changing nutrient availability. Notsurprisingly, many of these dILP actions require dFOXOand transcription. To summarize, these studies show thatregardless of location and timescale, insulin represents aversatile signal that works with other peptide signalingsystems to integrate nutritional status to regulate neuronaldevelopment and function.In some cases, dILP signaling outside of the nervoussystem does not involve dFOXO. Mutations in dFOXO donot abrogate the increase in oxidative stress resistance uponexposure to paraquat seen in animals with reduced insulinsignaling (Slack et al. 2011; Broughton et al. 2005), suggestinga transcription-independent role for insulin.Moreover, dFOXO does not seem to be required to promotefecundity, which in turn is influenced by insulinsignaling (Slack et al. 2011). Together, studies of longevityphenotypes provide support that insulin signaling usesdiverse downstream mechanisms for regulating somaticchanges. Molecular machinery other than dFOXO can alsomenengahi somatik perubahan ketika insulin sinyalterlibat.

Hasil (Bahasa Indonesia) 2:

Insulin sinyal pada lalat buah, D. melanogaster
mekanisme dan fungsi peptida insulin serupa
telah diamati di model organisme invertebrata lain,
D. melanogaster. Analisis genom telah mengungkapkan delapan
diduga Drosophila insulin-like peptide (dILP) prekursor
dengan struktur yang mirip dengan insulin mamalia (Brogiolo et al.
2001; Colombani et al 2012.). Kedelapan gen yang ditemukan
pada dua kromosom seperti ditunjukkan pada Gambar. 2a. dILPs 1-5 yang
ditemukan pada kromosom ketiga sebagai cluster gen, dILP-8 adalah
pada kromosom ketiga pada lokus sementara dILP 6 terpisah
dan 7 berada di kromosom X sebagai lokus terpisah (Brogiolo
et al, 2001;. Colombani et al. 2012). Orthologs ke
jalur insulin mamalia dan C. elegans juga telah
diidentifikasi termasuk dInR (reseptor insulin Drosophila),
chico dan lnk (IRS), PI3K dan Akt (Protein kinase B)
(Staveley et al 1998;.. Leevers et al 1996 ; Poltilove et al.
2000; Werz et al 2009).. Ekspresi kompleks dILPs di
D. melanogaster adalah spasial dan temporal diatur. Dalam
kaitannya dengan modulasi fungsi dan perilaku saraf, yang
sel neurosecretory median di otak lalat mengekspresikan
bagian dari dILPs (Brogiolo et al 2001;.. Rulifson et al, 2002).
Ablasi sel insulin hasil produksi dalam pertumbuhan
cacat dan konsentrasi karbohidrat misregulated di yang
hemolymph (Rulifson et al. 2002).
Serupa dengan hasil yang diperoleh dengan menggunakan C. elegans Model,
sinyal insulin dalam D. melanogaster juga telah ditunjukkan untuk
mengatur berbagai aspek pembangunan neuronal. Selama
pengembangan, sekelompok kecil sel neurosecretory median
melepaskan insulin ke dalam sistem peredaran darah dalam menanggapi
nutrisi (Ikeya et al. 2002). Beredar insulin bekerja pada
neuron dalam tubuh jamur dan mengatur makan
perilaku dan pertumbuhan larva lalat (Zhao dan Campos
2012). Dalam konteks ini, sumber dan identitas dILPs
yang bekerja pada tubuh jamur masih belum jelas. dILPs juga
memainkan peran penting dalam regulasi dinamis batang
pertumbuhan sel dalam menanggapi perubahan metabolik. Selama
pengembangan, sel-sel induk saraf diam di otak harus
diaktifkan kembali untuk proliferasi untuk menghasilkan neuron dewasa.
Status gizi dirasakan oleh sel-sel glial yang mengekspresikan dan
mengeluarkan dILPs. Lokal disekresikan dILP2 dan dILP6 dari glia
mengaktifkan kembali sel-sel induk saraf dengan bertindak pada PI3K / Akt
jalur (Cheetham dan Brand 2013). Singkatnya, ini
studi menunjukkan peran dILPs di kopling gizi
status perkembangan saraf dan pertumbuhan.
insulin juga telah ditunjukkan untuk lingkungan beberapa
kondisi untuk fisiologi pada lalat dewasa. D. melanogaster
S6 kinase yang terlibat dalam modulasi respon kelaparan oleh
mengatur efek yang berlawanan insulin dan neuropeptida
jalur F signaling (Wu et al. 2005). Rendahnya tingkat sirkulasi
insulin menyebabkan peningkatan ekspresi
kadar neuropeptida pendek reseptor F di sinaps
antara neuron reseptor penciuman dan proyeksi
neuron. Acara ini tergantung transkripsi, yang
dihambat oleh sinyal insulin, meningkatkan daya tarik
dewasa terbang ke makanan (Root et al. 2011). Hasil ini menunjukkan
bahwa dILPs diproduksi di status gizi beberapa otak dengan fungsi sirkuit saraf. Berbeda dengan C. elegans
temuan tindakan transkripsi-independen cepat ILPS,
skala waktu aksi insulin pada lalat dapat berkisar dari jam
ke hari untuk mengakomodasi perubahan ketersediaan hara. Tidak
mengherankan, banyak dari tindakan dILP ini membutuhkan dFOXO
dan transkripsi. Untuk meringkas, studi ini menunjukkan bahwa
terlepas dari lokasi dan skala waktu, insulin merupakan
sinyal serbaguna yang bekerja dengan peptida lain sinyal
sistem untuk mengintegrasikan status gizi untuk mengatur saraf
pengembangan dan fungsi.
Dalam beberapa kasus, dILP sinyal luar saraf
sistem tidak melibatkan dFOXO. Mutasi pada dFOXO jangan
tidak membatalkan kenaikan resistensi stres oksidatif pada
paparan paraquat terlihat pada hewan dengan mengurangi insulin
signaling (Slack et al 2011;.. Broughton et al 2005), menunjukkan
. peran transkripsi-independen untuk insulin
Selain itu, dFOXO tidak tampaknya tidak diperlukan untuk mempromosikan
fekunditas, yang pada gilirannya dipengaruhi oleh insulin
signaling (Slack et al. 2011). Bersama-sama, studi umur panjang
fenotip memberikan dukungan yang signaling insulin menggunakan
mekanisme hilir beragam untuk mengatur somatik
perubahan. Mesin molekul selain dFOXO juga dapat
memediasi perubahan somatik ketika sinyal insulin
yang terlibat.