| Blocking O-linked GlcNAc cycling in Drosophila insulin-producing cells perturbs glucose-insulin homeostasis. | |
| | |
MedLine Citation:
|
PMID: 20926386 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
A dynamic cycle of O-linked GlcNAc (O-GlcNAc) addition and removal is catalyzed by O-GlcNAc transferase and O-GlcNAcase, respectively, in a process that serves as the final step in a nutrient-driven "hexosamine-signaling pathway." Evidence points to a role for O-GlcNAc cycling in diabetes and insulin resistance. We have used Drosophila melanogaster to determine whether O-GlcNAc metabolism plays a role in modulating Drosophila insulin-like peptide (dilp) production and insulin signaling. We employed transgenesis to either overexpress or knock down Drosophila Ogt(sxc) and Oga in insulin-producing cells (IPCs) or fat bodies using the GAL4-UAS system. Knockdown of Ogt decreased Dilp2, Dilp3, and Dilp5 production, with reduced body size and decreased phosphorylation of Akt in vivo. In contrast, knockdown of Oga increased Dilp2, Dilp3, and Dilp5 production, increased body size, and enhanced phosphorylation of Akt in vivo. However, knockdown of either Ogt(sxc) or Oga in the IPCs increased the hemolymph carbohydrate concentration. Furthermore, phosphorylation of Akt stimulated by extraneous insulin in an ex vivo cultured fat body of third instar larvae was diminished in strains subjected to IPC knockdown of Ogt or Oga. Knockdown of O-GlcNAc cycling enzymes in the fat body dramatically reduced neutral lipid stores. These results demonstrate that altered O-GlcNAc cycling in Drosophila IPCs modulates insulin production and influences the insulin responsiveness of peripheral tissues. The observed phenotypes in O-GlcNAc cycling mimic pancreatic β-cell dysfunction and glucose toxicity related to sustained hyperglycemia in mammals. |
| | |
Authors:
|
Osamu Sekine; Dona C Love; David S Rubenstein; John A Hanover |
Related Documents
:
|
7499246 - A consensus insulin response element is activated by an ets-related transcription factor. 19883616 - Glucose shortens the life span of c. elegans by downregulating daf-16/foxo activity and... 11641236 - Defects of the insulin receptor substrate (irs) system in human metabolic disorders. 17038556 - Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of i... 7475056 - Insulin sensitivity in obese hypertensive dyslipidemic patients treated with enalapril ... 11554776 - Genetic susceptibility to macrovascular complications of type 2 diabetes mellitus. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2010-10-06 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Dec |
Date Detail:
|
Created Date: 2010-11-29 Completed Date: 2010-12-30 Revised Date: 2011-12-21 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 38684-91 Citation Subset: IM |
Affiliation:
|
Laboratory of Cell Biochemistry and Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acetylglucosamine
/
genetics,
metabolism* Animals Drosophila melanogaster Gene Knockdown Techniques Glucose / genetics, metabolism* Homeostasis / physiology* Insulin* |
| Chemical | |
Reg. No./Substance:
|
0/Insulin; 50-99-7/Glucose; 7512-17-6/Acetylglucosamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Identification of a residue in helix 2 of rice plasma membrane intrinsic proteins that influences wa...
Next Document: The eukaryotic translation elongation Factor 1Bgamma has a non-guanine nucleotide exchange factor ro...