title: O-linked-N-acetylglucosamine cycling and insulin signaling are required for the glucose stress response in Caenorhabditis elegans.
abstract: In a variety of organisms, including worms, flies, and mammals, glucose homeostasis is maintained by insulin-like signaling in a robust network of opposing and complementary signaling pathways. The hexosamine signaling pathway, terminating in O-linked-N-acetylglucosamine (O-GlcNAc) cycling, is a key sensor of nutrient status and has been genetically linked to the regulation of insulin signaling in Caenorhabditis elegans. Here we demonstrate that O-GlcNAc cycling and insulin signaling are both essential components of the C. elegans response to glucose stress. A number of insulin-dependent processes were found to be sensitive to glucose stress, including fertility, reproductive timing, and dauer formation, yet each of these differed in their threshold of sensitivity to glucose excess. Our findings suggest that O-GlcNAc cycling and insulin signaling are both required for a robust and adaptable response to glucose stress, but these two pathways show complex and interdependent roles in the maintenance of glucose-insulin homeostasis.
authors: Department of Biology, College of the Holy Cross, Worcester, Massachusetts 01610, USA.
authors: Michelle A
authors: MA
authors: Mondoux
authors: Dona C
authors: DC
authors: Love
authors: Salil K
authors: SK
authors: Ghosh
authors: Tetsunari
authors: T
authors: Fukushige
authors: Michelle
authors: M
authors: Bond
authors: Gayani R
authors: GR
authors: Weerasinghe
authors: John A
authors: JA
authors: Hanover
authors: Michael W
authors: MW
authors: Krause
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002241:Carbohydrates / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007814:Larva / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000032:analysis; D008297:Male; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects; D015398:Signal Transduction; D013312:Stress, Physiological; D013997:Time Factors; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002241:Carbohydrates; D007328:Insulin; D008055:Lipids; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; D005947:Glucose; D000117:Acetylglucosamine