title: Activation of central lactate metabolism lowers glucose production in uncontrolled diabetes and diet-induced insulin resistance.
abstract: OBJECTIVE
  Hypothalamic lactate metabolism lowers hepatic glucose production and plasma glucose levels in normal rodents. However, it remains unknown whether activation of hypothalamic lactate metabolism lowers glucose production and plasma glucose levels in rodents with diabetes and obesity.
  
  
  METHODS
  We performed intracerebroventricular (ICV) administration of lactate to enhance central lactate metabolism in 1) early-onset streptozotocin-induced uncontrolled diabetic rodents, 2) experimentally induced hypoinsulinemic normal rodents, and 3) early-onset diet-induced insulin-resistant rodents. Tracer-dilution methodology was used to assess the impact of ICV lactate on the rate of glucose production in all three models.
  
  
  RESULTS
  We first report that in the absence of insulin treatment, ICV lactate administration lowered glucose production and glucose levels in rodents with uncontrolled diabetes. Second, ICV lactate administration lowered glucose production and glucose levels in normal rodents with experimentally induced hypoinsulinemia. Third, and finally, ICV lactate administration lowered glucose production in normal rodents with diet-induced insulin resistance.
  
  
  CONCLUSIONS
  Central lactate metabolism lowered glucose production in uncontrolled diabetic and normal rodents with hypoinsulinemia and in rodents with diet-induced insulin resistance. These data suggest that insulin signaling is not required for central lactate to lower glucose production and that the activation of hypothalamic lactate metabolism could consequently bypass insulin resistance and lower glucose levels in early-onset diabetes and obesity.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Madhu
authors.initials: M
authors.lastname: Chari
authors.forename: Carol K L
authors.initials: CK
authors.lastname: Lam
authors.forename: Penny Y T
authors.initials: PY
authors.lastname: Wang
authors.forename: Tony K T
authors.initials: TK
authors.lastname: Lam
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004041:Dietary Fats; D002149:Energy Intake; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D007262:Infusions, Intravenous; D007328:Insulin / Q000172:deficiency*; D007333:Insulin Resistance / Q000502:physiology*; D007773:Lactates / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D007773:Lactates; D005947:Glucose