Item – Theses Canada

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OCLC number
766376137
Link(s) to full text
LAC copy
LAC copy
Author
Chari, Madhu,1985-
Title
Central nervous system (CNS) nutrient sensing in diabetes.
Degree
M. Sc. -- University of Toronto, 2009
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2010]
Description
2 microfiches
Notes
Includes bibliographical references.
Abstract
An acute increase in hypothalamic glucose and its downstream metabolite lactate lower glucose production (GP) and plasma glucose (PG) levels in normal rodents. However, the effectiveness of this nutrient-sensing mechanism in metabolic disease is unknown. We assessed the effects of intracerebroventricular (i.c.v.) or intra-hypothalamic glucose and lactate on 'in vivo' glucose kinetics in conscious rats. Study I revealed that i.c.v. lactate lowered PG via a suppression of GP in rodents with uncontrolled diabetes and diet-induced insulin resistance. Study II demonstrated that i.c.v. glucose was ineffective at suppressing GP in uncontrolled diabetic rodents or rodents with a prior 24 h whole-body or hypothalamic hyperglycemic insult. When PG levels ' per se' were normalized in diabetic rodents hypothalamic glucose sensing to lower GP was rescued. As such, sustained hyperglycemia 'per se' impairs hypothalamic glucose effectiveness in diabetes. Further studies are necessary to determine defective mechanisms upstream of lactate metabolism hindering CNS glucose sensing.
ISBN
9780494593264
0494593261