Thalamic activation during slightly subphysiological glycemia in humans.
OBJECTIVE
The central nervous system mechanisms of defenses against falling plasma glucose concentrations, and how they go awry and result in iatrogenic hypoglycemia in diabetes, are not known. Hypoglycemic plasma glucose concentrations of 55 mg/dL (3.0 mmol/L) cause symptoms, activate glucose counterregulatory systems, and increase synaptic activity in a network of brain regions including the dorsal midline thalamus in humans. We tested the hypothesis that slightly subphysiological plasma glucose concentrations of 65 mg/dL (3.6 mmol/L), which do not cause symptoms but do activate glucose counterregulatory systems, also activate brain synaptic activities.


METHODS
We measured relative regional cerebral blood flow (rCBF), an index of synaptic activity, in predefined brain regions with [(15)O]water positron emission tomography, symptoms, and plasma epinephrine and glucagon concentrations during a 2-h euglycemic (90 mg/dL) to hypoglycemic (55 mg/dL) clamp (n = 20) or a 2-h euglycemic to slight subphysiological (65 mg/dL) clamp (n = 9) in healthy humans.


RESULTS
Clamped plasma glucose concentrations of 65 mg/dL did not cause hypoglycemic symptoms, but raised plasma epinephrine and glucagon concentrations and increased rCBF (P = 0.007) only in the dorsal midline thalamus.


CONCLUSIONS
Slightly subphysiological plasma glucose concentrations increase synaptic activity in the dorsal midline thalamus in humans.
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA. arbelaez_a@kids.wustl.edu
Ana María
AM
Arbeláez
Jerrel R
JR
Rutlin
Tamara
T
Hershey
William J
WJ
Powers
Tom O
TO
Videen
Philip E
PE
Cryer
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004837:Epinephrine / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D006801:Humans; D008297:Male; D013788:Thalamus / Q000378:metabolism*
D001786:Blood Glucose; D005934:Glucagon; D004837:Epinephrine