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Hypoglycemia Stimulates the Local Production of Lactate in the Ventromedial Hypothalamus

Semester: Summer 2023

Presentation description

Hypoglycemia remains a major problem in the clinical management of type 1 diabetes. The detection of hypoglycemia and initiation of the counter-regulatory hormone responses to correct it involve complex glucose-sensing mechanisms in the brain, more specifically, in the ventromedial hypothalamus (VMH). Chronically elevated blood glucose levels in poorly-controlled diabetes leads to failure of the counter-regulatory response- a phenomenon attributable to elevated brain lactate levels that prevent the VMH from detecting falling blood glucose levels. However, it is not clear whether lactate in the brain of diabetic animals is produced locally by astrocytes or transported into the brain from the periphery. To address whether hyperglycemia stimulates VMH lactate production, we bolused 1 g/kg of glucose into the jugular vein of non-diabetic Sprague Dawley rats to raise peripheral glucose and lactate levels and utilized microdialysis to monitor changes in VMH glucose and lactate concentrations over a 120-minute time frame. To determine whether lactate is produced by astrocytes, we administered oxamate into the VMH to inhibit lactate production (N=5). Control animals were given artificial extracellular fluid (N=7). The glucose bolus raised plasma glucose and lactate concentrations to the same extent. However, noticeable differences in VMH lactate levels were observed where oxamate treatment suppressed VMH lactate levels (P<0.05 vs controls). We conclude that, in the setting of acute hyperglycemia, lactate is locally produced within the VMH. Further experiments are needed to evaluate this mechanism under chronic hyperglycemic conditions and its impact on the counter-regulatory hormone response to hypoglycemia.

Presenter Name: Malique Valle

Presentation Type: Poster
Presentation Format: In Person
Presentation #116
College: Medicine
School / Department: Internal Medicine
Research Mentor: Owen Chan
Date | Time: Thursday, Aug 3rd | 10:30 AM