Document Detail

Activation of central lactate metabolism lowers glucose production in uncontrolled diabetes and diet-induced insulin resistance.
MedLine Citation:
PMID:  18184925     Owner:  NLM     Status:  MEDLINE    
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. RESEARCH DESIGN AND 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.
Madhu Chari; Carol K L Lam; Penny Y T Wang; Tony K T Lam
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-01-09
Journal Detail:
Title:  Diabetes     Volume:  57     ISSN:  1939-327X     ISO Abbreviation:  Diabetes     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-31     Completed Date:  2008-04-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  836-40     Citation Subset:  AIM; IM    
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
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MeSH Terms
Blood Glucose / drug effects,  metabolism
Diabetes Mellitus, Experimental / metabolism*
Dietary Fats
Energy Intake
Glucose / administration & dosage,  metabolism*
Infusions, Intravenous
Insulin / deficiency*
Insulin Resistance / physiology*
Lactates / metabolism*,  pharmacology
Rats, Sprague-Dawley
Reg. No./Substance:
0/Blood Glucose; 0/Dietary Fats; 0/Lactates; 11061-68-0/Insulin; 50-99-7/Glucose

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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