Novel studies on Drosophila melanogaster model reveal the roles of JNK-Jak/STAT axis and intestinal microbiota in insulin resistance

References

• Roglic G. WHO global report on diabetes: a summary. Int J Non-Commun Dis. 2016;1(1):3.
   Google Scholar
• Lourido F, Quenti D, Salgado-Canales D, et al. Domeless receptor loss in fat body tissue reverts insulin resistance induced by a high-sugar diet in Drosophila melanogaster. Sci Rep. 2021;11(1):3263.
   PubMed Web of Science ®Google Scholar
• Goldstein BJ. Insulin resistance as the core defect in type 2 diabetes mellitus. Am J Cardiol. 2002;90(5):3–10.
   Google Scholar
• Shoelson SE, Herrero L, Naaz A, et al. Obesity, inflammation, and insulin resistance. Gastroenterology. 2007;132(6):2169–2180.
   PubMed Web of Science ®Google Scholar
• Schellenberg ES, Dryden DM, Vandermeer B, et al. Lifestyle interventions for patients with and at risk for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013;159(8):543–551.
   PubMed Web of Science ®Google Scholar
• Foley KP, Zlitni S, Denou E, et al. Long term but not short term exposure to obesity related microbiota promotes host insulin resistance. Nat Commun. 2018;9(1):1–15.
   PubMedGoogle Scholar
• Musial B, Vaughan O, Sferruzzi-Perri A, et al. A diet high in sugar and fat alters the insulin signalling in the mouse placenta. Placenta. 2014;35(9):A70.
   PubMed Web of Science ®Google Scholar
• Winzell MS, Ahren B. The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes. 2004;53(Supplement 3):S215–S219.
   PubMedGoogle Scholar
• Musselman LP, Fink JL, Narzinski K, et al. A high-sugar diet produces obesity and insulin resistance in wild-type drosophila. Dis Model Mech. 2011;4(6):842–849.
   PubMed Web of Science ®Google Scholar
• Alfa RW, Kim SK. Using drosophila to discover mechanisms underlying type 2 diabetes. Dis Model Mech. 2016;9(4):365–376.
   PubMed Web of Science ®Google Scholar
• Liggett MR, Hoy MJ, Mastroianni M, et al. High-glucose diets have sex-specific effects on aging in C. elegans: toxic to hermaphrodites but beneficial to males. Aging. 2015;7(6):383–388.
   PubMedGoogle Scholar
• Guo S. Insulin signaling, resistance, and metabolic syndrome: insights from mouse models into disease mechanisms. J Endocrinol. 2014;220(2):T1–T23.
   PubMed Web of Science ®Google Scholar
• Yu S, Zhang G, Jin LH. A high-sugar diet affects cellular and humoral immune responses in drosophila. Exp Cell Res. 2018;368(2):215–224.
   PubMed Web of Science ®Google Scholar
• Weina T, Ying L, Yiwen W, et al. What we have learnt from drosophila model organism: the coordination between insulin signaling pathway and tumor cells. Heliyon. 2022;8(7):e09957.
   PubMed Web of Science ®Google Scholar
• Gupta D. Peptidoglycan recognition proteins—maintaining immune homeostasis and normal development. Cell Host Microbe. 2008;3(5):273–274.
   PubMed Web of Science ®Google Scholar
• Chimnaronk S, Sitthiroongruang J, Srisucharitpanit K, et al. The crystal structure of JNK from Drosophila melanogaster reveals an evolutionarily conserved topology with that of mammalian JNK proteins. BMC Struct Biol. 2015;15(1):1–7.
   PubMedGoogle Scholar
• Arbouzova NI, Zeidler MP. JAK/STAT signalling in drosophila: insights into conserved regulatory and cellular functions. 2006.
   Google Scholar
• Inoue YH, Katsube H, Hinami Y. Drosophila models to investigate insulin action and mechanisms underlying human diabetes mellitus. 2018.
   Google Scholar
• Baker KD, Thummel CS. Diabetic larvae and obese flies—emerging studies of metabolism in drosophila. Cell Metab. 2007;6(4):257–266.
   PubMed Web of Science ®Google Scholar
• Alfa RW, Park S, Skelly K-R, et al. Suppression of insulin production and secretion by a decretin hormone. Cell Metab. 2015;21(2):323–334.
   PubMed Web of Science ®Google Scholar
• Musso G, Gambino R, Cassader M. Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes. Annu Rev Med. 2011;62:361–380.
   PubMed Web of Science ®Google Scholar
• Hirosumi J, Tuncman G, Chang L, et al. A central role for JNK in obesity and insulin resistance. Nature. 2002;420(6913):333–336.
   PubMed Web of Science ®Google Scholar
• Bako HY, Ibrahim MA, Isah MS, et al. Inhibition of JAK-STAT and NF-κB signalling systems could be a novel therapeutic target against insulin resistance and type 2 diabetes. Life Sci. 2019;239:117045.
   PubMed Web of Science ®Google Scholar
• Ikeya T, Galic M, Belawat P, et al. Nutrient-dependent expression of insulin-like peptides from neuroendocrine cells in the CNS contributes to growth regulation in drosophila. Curr Biol. 2002;12(15):1293–1300.
   PubMed Web of Science ®Google Scholar
• Kim SK, Rulifson EJ. Conserved mechanisms of glucose sensing and regulation by drosophila corpora cardiaca cells. Nature. 2004;431(7006):316–320.
   PubMed Web of Science ®Google Scholar
• Kim J, Neufeld TP. Dietary sugar promotes systemic TOR activation in drosophila through AKH-dependent selective secretion of Dilp3. Nat Commun. 2015;6(1):1–10.
   Google Scholar
• Post S, Karashchuk G, Wade JD, et al. Drosophila insulin-like peptides DILP2 and DILP5 differentially stimulate cell signaling and glycogen phosphorylase to regulate longevity. Front Endocrinol (Lausanne). 2018;9:245.
   PubMed Web of Science ®Google Scholar
• Géminard C, Rulifson EJ, Léopold P. Remote control of insulin secretion by fat cells in drosophila. Cell Metab. 2009;10(3):199–207.
   PubMed Web of Science ®Google Scholar
• Rambur A, Lours-Calet C, Beaudoin C, et al. Sequential ras/MAPK and PI3K/AKT/mTOR pathways recruitment drives basal extrusion in the prostate-like gland of drosophila. Nat Commun. 2020;11(1):1–12.
   PubMed Web of Science ®Google Scholar
• Hay N. Interplay between FOXO, TOR, and akt. Biochim Biophys Acta. 2011;1813(11):1965–1970.
   PubMed Web of Science ®Google Scholar
• Jünger MA, Rintelen F, Stocker H, et al. The drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J Biol. 2003;2(3):20–17.
   PubMedGoogle Scholar
• Dae Hyun K, Zhang T, Sojin L, et al. FoxO6 in glucose metabolism. J Diabetes. 2013;5(3):233–240.
   PubMed Web of Science ®Google Scholar
• Puig O, Tjian R. Transcriptional feedback control of insulin receptor by dFOXO/FOXO1. Genes Dev. 2005;19(20):2435–2446.
   PubMed Web of Science ®Google Scholar
• Moshapa FT, Riches-Suman K, Palmer TM. Therapeutic targeting of the proinflammatory IL-6-JAK/STAT signalling pathways responsible for vascular restenosis in type 2 diabetes mellitus. Cardiol Res Pract. 2019;2019:9846312.
   PubMed Web of Science ®Google Scholar
• Dongre UJ. Adipokines in insulin resistance: current updates. Biosci, Biotech Res Asia. 2021;18(2):357–366.
   Google Scholar
• Oldefest M, Nowinski J, Hung C-W, et al. Upd3 – an ancestor of the four-helix bundle cytokines. Biochem Biophys Res Commun. 2013;436(1):66–72.
   PubMed Web of Science ®Google Scholar
• Jiang H, Patel PH, Kohlmaier A, et al. Cytokine/jak/stat signaling mediates regeneration and homeostasis in the drosophila midgut. Cell. 2009;137(7):1343–1355.
   PubMed Web of Science ®Google Scholar
• Ding G, Xiang X, Hu Y, et al. Coordination of tumor growth and host wasting by tumor-derived Upd3. Cell Rep. 2021;36(7):109553.
   PubMed Web of Science ®Google Scholar
• Micchelli CA, Perrimon N. Evidence that stem cells reside in the adult drosophila midgut epithelium. Nature. 2006;439(7075):475–479.
   PubMed Web of Science ®Google Scholar
• Ohlstein B, Spradling A. The adult drosophila posterior midgut is maintained by pluripotent stem cells. Nature. 2006;439(7075):470–474.
   PubMed Web of Science ®Google Scholar
• Zhang X, Jin Q, Jin LH. High sugar diet disrupts gut homeostasis though JNK and STAT pathways in drosophila. Biochem Biophys Res Commun. 2017;487(4):910–916.
   PubMed Web of Science ®Google Scholar
• Yamanaka Y, Wilson EM, Rosenfeld RG, et al. Inhibition of insulin receptor activation by insulin-like growth factor binding proteins. J Biol Chem. 1997;272(49):30729–30734.
   PubMed Web of Science ®Google Scholar
• Honegger B, Galic M, Köhler K, et al. Imp-L2, a putative homolog of vertebrate IGF-binding protein 7, counteracts insulin signaling in drosophila and is essential for starvation resistance. J Biol. 2008;7(3):10–11.
   PubMedGoogle Scholar
• Figueroa-Clarevega A, Bilder D. Malignant drosophila tumors interrupt insulin signaling to induce cachexia-like wasting. Dev Cell. 2015;33(1):47–55.
   PubMed Web of Science ®Google Scholar
• Jimenez-Gomez Y, Mattison JA, Pearson KJ, et al. Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on high-fat, high-sugar diet. Cell Metab. 2013;18(4):533–545.
   PubMed Web of Science ®Google Scholar
• von Frieling J, Faisal MN, Sporn F, et al. A high-fat diet induces a microbiota-dependent increase in stem cell activity in the drosophila intestine. PLoS Genet. 2020;16(5):e1008789.
   PubMed Web of Science ®Google Scholar
• Chen L-W, Wu Y-Y, Chung P-H, et al. Microbiota enhances intestinal immunity through JNK/ROS pathways (MUC4P. 838). Am Assoc Immnol. 2014;192(Supplement 1):133–114.
   Google Scholar
• Mukherji A, Kobiita A, Ye T, et al. Homeostasis in intestinal epithelium is orchestrated by the circadian clock and microbiota cues transduced by TLRs. Cell. 2013;153(4):812–827.
   PubMed Web of Science ®Google Scholar
• Maillet F, Bischoff V, Vignal C, et al. The drosophila peptidoglycan recognition protein PGRP-LF blocks PGRP-LC and IMD/JNK pathway activation. Cell Host Microbe. 2008;3(5):293–303.
   PubMed Web of Science ®Google Scholar
• Chevée V, Sachar U, Yadav S, et al. The peptidoglycan recognition protein PGRP-LE regulates the drosophila immune response against the pathogen photorhabdus. Microb Pathog. 2019;136:103664.
   PubMed Web of Science ®Google Scholar
• Michel T, Reichhart J-M, Hoffmann JA, et al. Drosophila toll is activated by gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature. 2001;414(6865):756–759.
   PubMed Web of Science ®Google Scholar
• Bischoff V, Vignal C, Boneca IG, et al. Function of the drosophila pattern-recognition receptor PGRP-SD in the detection of gram-positive bacteria. Nat Immunol. 2004;5(11):1175–1180.
   PubMed Web of Science ®Google Scholar
• Gobert V, Gottar M, Matskevich AA, et al. Dual activation of the drosophila toll pathway by two pattern recognition receptors. Science. 2003;302(5653):2126–2130.
   PubMed Web of Science ®Google Scholar
• Hedengren M, Dushay MS, Ando I, et al. Relish, a Central factor in the control of humoral but not cellular immunity in drosophila. Mol Cell. 1999;4(5):827–837.
   PubMed Web of Science ®Google Scholar
• Zaidman-Rémy A, Hervé M, Poidevin M, et al. The drosophila amidase PGRP-LB modulates the immune response to bacterial infection. Immunity. 2006;24(4):463–473.
   PubMed Web of Science ®Google Scholar
• Persson C, Oldenvi S, Steiner H. Peptidoglycan recognition protein LF: a negative regulator of drosophila immunity. Insect Biochem Mol Biol. 2007;37(12):1309–1316.
   PubMed Web of Science ®Google Scholar
• Charroux B, Royet J. Drosophila immune response: from systemic antimicrobial peptide production in fat body cells to local defense in the intestinal tract. Fly (Austin). 2010;4(1):40–47.
   PubMed Web of Science ®Google Scholar
• Ryu J-H, Kim S-H, Lee H-Y, et al. Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in drosophila. Science. 2008;319(5864):777–782.
   PubMed Web of Science ®Google Scholar
• Roh SW, Nam Y-D, Chang H-W, et al. Phylogenetic characterization of two novel commensal bacteria involved with innate immune homeostasis in Drosophila melanogaster. Appl Environ Microbiol. 2008;74(20):6171–6177.
   PubMed Web of Science ®Google Scholar
• Shin SC, Kim S-H, You H, et al. Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling. Science. 2011;334(6056):670–674.
   PubMed Web of Science ®Google Scholar
• Storelli G, Defaye A, Erkosar B, et al. Lactobacillus plantarum promotes drosophila systemic growth by modulating hormonal signals through TOR-dependent nutrient sensing. Cell Metab. 2011;14(3):403–414.
   PubMed Web of Science ®Google Scholar
• Westfall S, Lomis N, Prakash S. Ferulic acid produced by Lactobacillus fermentum influences developmental growth through a dTOR-mediated mechanism. Mol Biotechnol. 2019;61(1):1–11.
   PubMed Web of Science ®Google Scholar
• Wang H, Cheng X, Zhang L, et al. A surface-layer protein from Lactobacillus acidophilus NCFM induces autophagic death in HCT116 cells requiring ROS-mediated modulation of mTOR and JNK signaling pathways. Food Funct. 2019;10(7):4102–4112.
   PubMed Web of Science ®Google Scholar
• Hakim J. Reactive oxygen species and inflammation. C R Seances Soc Biol Fil. 1993;187(3):286–295.
   PubMedGoogle Scholar
• El-Kenawi A, Ruffell B. Inflammation, ROS, and mutagenesis. Cancer Cell. 2017;32(6):727–729.
   PubMed Web of Science ®Google Scholar
• Griffith B, Pendyala S, Hecker L, et al. NOX enzymes and pulmonary disease. Antioxid Redox Signal. 2009;11(10):2505–2516.
   PubMed Web of Science ®Google Scholar
• Di Meo S, Iossa S, Venditti P. Skeletal muscle insulin resistance: role of mitochondria and other ROS sources. J Endocrinol. 2017;233(1):R15–R42.
   PubMed Web of Science ®Google Scholar
• Hotamisligil G. Inflammation and endoplasmic reticulum stress in obesity and diabetes. Int J Obes. 2008;32(S7):S52–S54.
   Google Scholar
• Zhu ZX, Cai WH, Wang T, et al. bFGF-regulating MAPKs are involved in high glucose-mediated ROS production and delay of vascular endothelial cell migration. PLoS One. 2015;10(12):e0144495.
   PubMed Web of Science ®Google Scholar
• Gao W, Du X, Lei L, et al. NEFA‐induced ROS impaired insulin signalling through the JNK and p38MAPK pathways in non‐alcoholic steatohepatitis. J Cell Mol Med. 2018;22(7):3408–3422.
   PubMed Web of Science ®Google Scholar
• Bayliak MM, Abrat OB, Storey JM, et al. Interplay between diet-induced obesity and oxidative stress: comparison between drosophila and mammals. Comp Biochem Physiol A Mol Integr Physiol. 2019;228:18–28.
   PubMed Web of Science ®Google Scholar
• Zhou J, Boutros M. JNK-dependent intestinal barrier failure disrupts host–microbe homeostasis during tumorigenesis. Proc Natl Acad Sci U S A. 2020;117(17):9401–9412.
   PubMed Web of Science ®Google Scholar
• Lemaitre B, Hoffmann J. The host defense of Drosophila melanogaster. Annu Rev Immunol. 2007;25:697–743.
   PubMed Web of Science ®Google Scholar
• Deng J, Zeng L, Lai X, et al. Metformin protects against intestinal barrier dysfunction via AMPKα1‐dependent inhibition of JNK signalling activation. J Cell Mol Med. 2018;22(1):546–557.
   PubMed Web of Science ®Google Scholar
• Jamar G, Ribeiro DA, Pisani LP. High-fat or high-sugar diets as trigger inflammation in the microbiota-gut-brain axis. Crit Rev Food Sci Nutr. 2021;61(5):836–854.
   PubMed Web of Science ®Google Scholar
• Ma T, Tian X, Zhang B, et al. Low-dose metformin targets the lysosomal AMPK pathway through PEN2. Nature. 2022;603(7899):159–165.
   PubMed Web of Science ®Google Scholar
• Zhang C-S, Hawley SA, Zong Y, et al. Fructose-1, 6-bisphosphate and aldolase mediate glucose sensing by AMPK. Nature. 2017;548(7665):112–116.
   PubMed Web of Science ®Google Scholar
• Supek F, Supekova L, Mandiyan S, et al. A novel accessory subunit for vacuolar H (+)-ATPase from chromaffin granules. J Biol Chem. 1994;269(39):24102–24106.
   PubMed Web of Science ®Google Scholar
• Clissold SP, Edwards C. Acarbose. Drugs. 1988;35(3):214–243.
   PubMed Web of Science ®Google Scholar
• Holman RR, Cull CA, Turner RC. A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (UK prospective diabetes study 44). Diabetes Care. 1999;22(6):960–964.
   PubMed Web of Science ®Google Scholar
• Mo D, Liu S, Ma H, et al. Effects of acarbose and metformin on the inflammatory state in newly diagnosed type 2 diabetes patients: a one-year randomized clinical study. Drug Des Devel Ther. 2019;13:2769–2776.
   PubMed Web of Science ®Google Scholar
• Mishra AK, Dingli D. Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells. Leukemia. 2019;33(11):2695–2709.
   PubMed Web of Science ®Google Scholar
• Cangoz S, Chang YY, Chempakaseril S, et al. The kidney as a new target for antidiabetic drugs: SGLT 2 inhibitors. J Clin Pharm Ther. 2013;38(5):350–359.
   PubMed Web of Science ®Google Scholar
• Plosker GL. Dapagliflozin. Drugs. 2012;72(17):2289–2312.
   PubMed Web of Science ®Google Scholar
• Kabel AM, Arab HH, Abd Elmaaboud MA. Effect of dapagliflozin and/or L‐arginine on solid tumor model in mice: the interaction between nitric oxide, transforming growth factor‐beta 1, autophagy, and apoptosis. Fundam Clin Pharmacol. 2021;35(6):968–978.
   PubMed Web of Science ®Google Scholar
• Kitade H, Sawamoto K, Nagashimada M, et al. CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage ­recruitment and M1/M2 status. Diabetes. 2012;61(7):1680–1690.
   PubMed Web of Science ®Google Scholar
• Dus M, Ai M, Suh GS. Taste-independent nutrient selection is mediated by a brain-specific Na+/solute co-transporter in drosophila. Nat Neurosci. 2013;16(5):526–528.
   PubMed Web of Science ®Google Scholar