Thalamic activation during slightly subphysiological glycemia in humans

Area of Science:

• Neuroscience
• Endocrinology
• Metabolism

Background:

• The brain's response to falling plasma glucose is crucial for maintaining homeostasis.
• Iatrogenic hypoglycemia in diabetes can result from dysregulated counterregulatory responses.
• Understanding central nervous system mechanisms is key to preventing hypoglycemia-related complications.

Purpose of the Study:

• To investigate if subphysiological plasma glucose concentrations (65 mg/dL) activate brain synaptic activity.
• To determine if mild hypoglycemia, without symptoms, triggers central nervous system responses.
• To explore the role of the dorsal midline thalamus in glucose regulation.

Main Methods:

• Utilized [(15)O]water positron emission tomography to measure relative cerebral blood flow (rCBF) as an index of synaptic activity.
• Employed a 2-hour clamp technique in healthy humans to maintain specific plasma glucose levels (euglycemic, hypoglycemic, or subphysiological).
• Monitored symptoms, plasma epinephrine, and glucagon concentrations alongside rCBF.

Main Results:

• Plasma glucose levels of 65 mg/dL did not induce hypoglycemic symptoms.
• Mildly subphysiological glucose concentrations significantly increased rCBF in the dorsal midline thalamus (P = 0.007).
• Elevated plasma epinephrine and glucagon concentrations were observed at 65 mg/dL, indicating counterregulatory activation.

Conclusions:

• Slightly subphysiological plasma glucose concentrations activate synaptic activity in the human dorsal midline thalamus.
• The dorsal midline thalamus plays a role in sensing and responding to mild decrements in plasma glucose.
• These findings shed light on the brain's intricate mechanisms for glucose homeostasis.