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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/18251

Title: Central Nervous System (CNS) Nutrient Sensing in Diabetes
Authors: Chari, Madhu
Advisor: Lam, Tony K. T.
Department: Physiology
Keywords: Diabetes
Glucose Production
Hypothalamus
Rodent
Issue Date: 13-Jan-2010
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.
URI: http://hdl.handle.net/1807/18251
Appears in Collections:Master
Department of Physiology - Master theses

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