RRC ID 45963
Author Dwyer DS, Aamodt EJ.
Title Insulin/IGF-1 signaling, including class II/III PI3Ks, β-arrestin and SGK-1, is required in C. elegans to maintain pharyngeal muscle performance during starvation.
Journal PLoS ONE
Abstract In C. elegans, pharyngeal pumping is regulated by the presence of bacteria. In response to food deprivation, the pumping rate rapidly declines by about 50-60%, but then recovers gradually to baseline levels on food after 24 hr. We used this system to study the role of insulin/IGF-1 signaling (IIS) in the recovery of pharyngeal pumping during starvation. Mutant strains with reduced function in the insulin/IGF-1 receptor, DAF-2, various insulins (INS-1 and INS-18), and molecules that regulate insulin release (UNC-64 and NCA-1; NCA-2) failed to recover normal pumping rates after food deprivation. Similarly, reduction or loss of function in downstream signaling molecules (e.g., ARR-1, AKT-1, and SGK-1) and effectors (e.g., CCA-1 and UNC-68) impaired pumping recovery. Pharmacological studies with kinase and metabolic inhibitors implicated class II/III phosphatidylinositol 3-kinases (PI3Ks) and glucose metabolism in the recovery response. Interestingly, both over- and under-activity in IIS was associated with poorer recovery kinetics. Taken together, the data suggest that optimum levels of IIS are required to maintain high levels of pharyngeal pumping during starvation. This work may ultimately provide insights into the connections between IIS, nutritional status and sarcopenia, a hallmark feature of aging in muscle.
Volume 8(5)
Pages e63851
Published 2013
DOI 10.1371/journal.pone.0063851
PII PONE-D-13-02901
PMID 23700438
PMC PMC3659082
MeSH Animals Arrestins / metabolism* Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Calcium Channel Blockers / pharmacology Calcium Channels / metabolism Chromones / pharmacology Food Deprivation Gene Knockout Techniques Insulin / physiology* Insulin-Like Growth Factor I / physiology* Morpholines / pharmacology Muscle Contraction Mutation Pharyngeal Muscles / physiology* Phosphatidylinositol 3-Kinases / antagonists & inhibitors Phosphatidylinositol 3-Kinases / metabolism* Phosphorylation Protein Processing, Post-Translational Protein-Serine-Threonine Kinases / metabolism* Receptor, Insulin / genetics Receptor, Insulin / metabolism Signal Transduction Stress, Physiological Syntaxin 1 / genetics Syntaxin 1 / metabolism beta-Arrestins
IF 2.766
Times Cited 6
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
C.elegans tm1888