title: Insulin increases ceramide synthesis in skeletal muscle.
abstract: OBJECTIVE
  The purpose of this study was to determine the effect of insulin on ceramide metabolism in skeletal muscle.
  
  
  METHODS
  Skeletal muscle cells were treated with insulin with or without palmitate for various time periods. Lipids (ceramides and TAG) were isolated and gene expression of multiple biosynthetic enzymes were quantified. Additionally, adult male mice received daily insulin injections for 14 days, followed by muscle ceramide analysis.
  
  
  RESULTS
  In muscle cells, insulin elicited an increase in ceramides comparable to palmitate alone. This is likely partly due to an insulin-induced increase in expression of multiple enzymes, particularly SPT2, which, when knocked down, prevented the increase in ceramides. In mice, 14 days of insulin injection resulted in increased soleus ceramides, but not TAG. However, insulin injections did significantly increase hepatic TAG compared with vehicle-injected animals.
  
  
  CONCLUSIONS
  This study suggests that insulin elicits an anabolic effect on sphingolipid metabolism in skeletal muscle, resulting in increased ceramide accumulation. These findings reveal a potential mechanism of the deleterious consequences of the hyperinsulinemia that accompanies insulin resistance and suggest a possible novel therapeutic target to mitigate its effects.
authors.affiliation: Department of Physiology and Developmental Biology, 593 WIDB, Brigham Young University, Provo, UT 84602, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Hansen
authors.affiliation: Department of Physiology and Developmental Biology, 593 WIDB, Brigham Young University, Provo, UT 84602, USA.
authors.forename: T S
authors.initials: TS
authors.lastname: Tippetts
authors.affiliation: Department of Physiology and Developmental Biology, 593 WIDB, Brigham Young University, Provo, UT 84602, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Anderson
authors.affiliation: Department of Physiology and Developmental Biology, 593 WIDB, Brigham Young University, Provo, UT 84602, USA.
authors.forename: Z E
authors.initials: ZE
authors.lastname: Holub
authors.affiliation: Department of Physiology and Developmental Biology, 593 WIDB, Brigham Young University, Provo, UT 84602, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Moulton
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Swensen
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Prince
authors.affiliation: Department of Physiology and Developmental Biology, 593 WIDB, Brigham Young University, Provo, UT 84602, USA.
authors.forename: B T
authors.initials: BT
authors.lastname: Bikman
mesh_terms: D000818:Animals; D002460:Cell Line; D002518:Ceramides / Q000096:biosynthesis*; D056488:Histone Chaperones / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology; D010168:Palmitates / Q000737:chemistry; D016133:Polymerase Chain Reaction; D013107:Sphingolipids / Q000737:chemistry
chemical_list: D002518:Ceramides; D056488:Histone Chaperones; D007328:Insulin; D008055:Lipids; D010168:Palmitates; D013107:Sphingolipids; C000595380:Spt2 protein, mouse