Table 1 Factors that act upon IPCs in the larva, the adult, or both
IPC-influencing factorLarval dataAdult data
Adipokinetic hormone (Akh)Akh from the CC mediates trehalose-induced release of DILP3 but not DILP2; Kim and Neufeld (2015).No adult data
AdipoR ligand (unknown)Ligand and source unknown; AdipoR in IPCs regulates DILP secretion and metabolism, but has no effect on body size; Kwak et al. (2013).Ligand and source unknown; IPC AdipoR regulates metabolism, survival, Dilp3 expression, and DILP release; Kwak et al. (2013).
Autonomous sugar sensingNo; sensing occurs via Akh relay; Kim and Neufeld (2015).Yes, through a mechanism involving inhibition of KATP channels and Ca2+ increase; Kréneisz et al. (2010).
Autonomous amino acid sensingVia leucine transporters Minidiscs and JhI-21 and the GDH pathway; Manière et al. (2016); Ziegler et al. (2018).No adult data.
Allatostatin A (AstA)AstA-R2 regulates both IPCs and APCs; Bowser and Tobe (2005); Hentze et al. (2015). AstA-R1 regulates DILP2/5 release but not expression; Deveci et al. (2019).AstA-R2 regulates both IPCs and APCs. AstA-R2 RNAi in IPCs downregulates Dilp2 but not Dilp3, in females but not males; Hentze et al. (2015).
CCHamide-2 (CCHa2)From gut and fat; regulated by dietary sugar and TOR; via CCHa2-R, promotes DILP2 and DILP5 release and Dilp5 expression; Ren et al. (2015); Sano et al. (2015).CCHa2 null affects insulin expression in the pupa via an undetermined route; Ren et al. (2015).
Dawdle (Daw)Daw from undetermined source(s) promotes DILP release, probably indirectly; Ghosh and O’Connor (2014).Dawdle signaling in muscle remotely promotes insulin release via an unknown route; Bai et al. (2013).
DILPs (via InR)No larval data on DILP-specific feedback.IPC DILPs and fat-body DILP6 regulate one another; Gronke et al. (2010); Bai et al. (2012).
DILP8GCL neurons presynaptic to IPCs inhibit Dilp3 and Dilp5 expression; Vallejo et al. (2015).No adult data.
DopamineNo larval data.DopR1-RNAi in IPCs prevents dormancy; Andreatta et al. (2018).
EcdysoneDominant negative EcR in IPCs appears to block DILP release; Buhler et al. (2018).No adult data.
Eiger (Egr)Released from the fat body under starvation; acts via Grindelwald receptor to inhibit DILP2/5 release; Agrawal et al. (2016).No adult IPC data.
Female-specific independent of Transformer (FIT)Not expressed in larvae; Sun et al. (2017).From fat body of head; induced by protein feeding via TOR; affects IPCs through unknown route; Sun et al. (2017).
GABAGABA-B-R2 is present in IPCs, but RNAi does not alter size; Enell et al. (2010).GABA-B-R2 is present in adult IPCs, and RNAi leads to increased anti-DILP staining, altered metabolism, and increased stress sensitivity; Enell et al. (2010).
Growth-blocking peptides (GBPs)Expressed in fat body in response to amino acids and TOR; act via EGFR-expressing “IPC-connecting neurons”; Koyama and Mirth (2016); Meschi et al. (2019).GBP receptor Mthl10 is expressed in IPCs; global Mthl10 RNAi blocks DILP2 release from IPCs, at least indirectly, Mthl10 is broadly expressed; Sung et al. (2017).
Hugin (Hug)Subesophageal-zone Hugin neurons synapse on the IPCs, which express the Hugin receptor PK2-R1; Schlegel et al. (2016).No adult data.
Hypoxia (unknown signals)From fat body, primarily regulating Dilp3 expression and release of all DILPs; Texada et al. (2019a).No adult data.
Jelly Belly (Jeb)From cholinergic neurons, via Alk; Okamoto and Nishimura (2015).No adult data.
Leucokinin (Lk)No larval data.From neuronal source; receptor Lkr is expressed in IPCs and regulates Dilp expression, Zandawala et al. (2018); and sleep, Yurgel et al. (2019).
Limostatin (Lst)No larval data.From CC in response to carbohydrate restriction; suppresses DILP expression and release via PK1-R (LstR); Alfa et al. (2015).
Lipid particlesLipids from yeast but not plants cause particle accumulation on DILP2-recruiting neurons presynaptic to IPCs, and this increases DILP release; Brankatschk et al. (2014).No adult data.
Octopamine/tyramineOamb-RNAi does not alter adult size; Luo et al. (2014).Receptor OAMB is expressed in IPCs and regulates sleep and metabolism; Crocker et al. (2010); Erion et al. (2012). Oamb-RNAi increases Dilp3 expression; Luo et al. (2014).
Pigment-dispersing factor (PDF)No larval data.PDF from clock neurons increases cAMP levels via PDFR to block dormancy; Nagy et al. (2019).
Serotonin5-HT1A-GAL4 is not expressed in feeding third-instar larval IPCs, and 5-HT1A-RNAi animals are of normal size; Luo et al. (2012).5-HT1A-GAL4 is expressed in IPCs; 5-HT1-RNAi leads to increased DILP staining in IPCs and reduces starvation survival; Luo et al. (2012); 5-HT1A-RNAi increases expression of Dilp2 and Dilp5; Luo et al. (2014); Andreatta et al. (2018).
Short neuropeptide F (sNPF)sNPF peptides 1 and 2, but not 3 or 4, act on IPCs via sNPF-R (shown via anti-sNPF-R) and govern Dilp expression; Lee et al. (2008); Lee et al. (2009). However, IPCs do not express sNPF-R-GAL4; Kapan et al. (2012); Carlsson et al. (2013) (same line in both).IPCs express sNPF-R-GAL4; Kapan et al. (2012). sNPF from sugar-sensitive upstream neurons activates the IPCs and inhibits the APCs via sNPF-R; Oh et al. (2019). sNPF from clock neurons increases cAMP and Ca2+ levels, likely directly, to block dormancy; Nagy et al. (2019). Bidirectional sNPF/DILP feedback governs feeding; Sudhakar et al. (2020). See larval papers as well.
Stunted (Sun)Expressed in fat body in response to feeding via Spargel/PGC1, not via TOR. TOR does promote translation or release. Acts via Methuselah receptor to promote DILP release; Delanoue et al. (2016).No adult data.
Tachykinin (Tk)TkR99D perhaps present in larval IPCs; Birse et al. (2011), but no functional data reported.Source undefined, but Tk+ neurons terminate near IPC projections; suppresses Dilp2 and promotes Dilp3 in starvation via TkR99D; Birse et al. (2011).
Taotie neuronsNo larval data.Activation of peptidergic Taotie neurons (named for a Chinese mythological “gluttonous ogre”) upstream of IPCs inhibits feeding and DILP release; Zhan et al. (2016).
TemperatureCold-activated sensory neurons presynaptic to the IPCs promote DILP expression and release; Li and Gong (2015).No adult data.
Unpaired-2 (Upd2)Expressed in fat body in response to sugars and lipids; acts via Domeless receptor in presynaptic GABAergic neurons; Rajan and Perrimon (2012).Expressed in fat body in response to sugars and lipids; acts via Domeless receptor in presynaptic GABAergic neurons; Rajan and Perrimon (2012).
  • APC, Akh-producing cell; CC, corpora cardiaca; EcR, ecdysone receptor; InR, insulin receptor; IPC, insulin-producing cell; RNAi, RNA interference.