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.
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.
authors.affiliation: Departments of Psychiatry and Pharmacology, Toxicology and Neuroscience, LSU Health Sciences Center, Shreveport, Louisiana, USA. ddwyer@lsuhsc.edu
authors.forename: Donard S
authors.initials: DS
authors.lastname: Dwyer
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Aamodt
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D005508:Food Deprivation; D055786:Gene Knockout Techniques; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D009119:Muscle Contraction; D009154:Mutation; D010609:Pharyngeal Muscles / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D050827:Syntaxin 1 / Q000235:genetics / Q000378:metabolism; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D029742:Caenorhabditis elegans Proteins; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002867:Chromones; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011972:Receptor, Insulin; D050827:Syntaxin 1; D000071557:beta-Arrestins; C494215:unc-64 protein, C elegans; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C107483:DAF-2 protein, C elegans; C540745:Sgk-1 protein, C elegans