title: Glucose-dependent insulin modulation of oscillatory lipolysis in perifused rat adipocytes.
abstract: OBJECTIVE
  We showed glucose-dependent lipolytic oscillations in adipocytes that are modulated by free fatty acids (FFAs). We hypothesized that the oscillations are driven by oscillatory glucose metabolism that leads to oscillatory formation of alpha-glycerophosphate (alpha-GP), oscillatory removal of long-chain coenzyme A (LC-CoA) by alpha-GP to form triglycerides, and oscillatory relief of LC-CoA inhibition of triglyceride lipases. This study examined the effect of insulin on this hypothesis.
  
  
  METHODS
  Samples were collected every minute from perifused rat adipocytes during the basal state followed by insulin (+/-glucose) or isoproterenol (+/-insulin; n = 4 each).
  
  
  RESULTS
  Insulin caused a significant increase in glycerol release (18%), with a concomitant significant decrease in FFA release (38%). Without glucose, insulin had no effect on glycerol release while still decreasing FFA release (35%). Insulin (5 microU/mL) attenuated the response of lipolysis to isoproterenol (approximately 3-fold increase with isoproterenol vs. 2-fold increase with insulin + isoproterenol). However, 1 mU/mL insulin amplified the lipolytic response ( approximately 5-fold increase in glycerol release with insulin + isoproterenol), with a concomitant increase in FFA reesterification (no increase in FFA release compared with isoproterenol alone).
  
  
  CONCLUSIONS
  We interpret these results to be due to insulin's ability to increase glucose uptake and conversion to alpha-GP, thus removing LC-CoA inhibition of triglyceride lipases. While the physiological importance of lipolytic oscillations remains to be determined, we hypothesize that such an oscillation may play an important role in the delivery of FFAs to the liver, beta cells, and other tissues.
authors.affiliation: Obesity Research Center, Boston Medical Center, MA 02118, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Getty-Kaushik
authors.forename: Ann-Marie T
authors.initials: AM
authors.lastname: Richard
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Corkey
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005947:Glucose / Q000502:physiology*; D005990:Glycerol / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000214:Acyl Coenzyme A; D000318:Adrenergic beta-Agonists; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D007773:Lactates; D005947:Glucose; D007545:Isoproterenol; D005990:Glycerol