Post-hypoglycaemic hyperketonaemia does not contribute to brain metabolism during insulin-induced hypoglycaemia in humans.
It is controversial as to whether ketone bodies are utilized by the human brain as a fuel alternative to glucose during hypoglycaemia. To clarify the issue, we studied 10 normal volunteers during an experimental hypoglycaemia closely mimicking the clinical hypoglycaemia of patients with Type 1 (insulin-dependent) diabetes mellitus or insulinoma. Hypoglycaemia was induced by a continuous infusion of insulin (0.40 mU.kg-1.min-1 for 8 h, plasma insulin approximately 180 pmol/l) which decreased the plasma glucose concentration to approximately 3.1 mmol/l during the last 3 h of the studies. Subjects were studied on two occasions, i.e. spontaneous, counterregulatory-induced post-hypoglycaemic increase in 3-beta-hydroxybutyrate (from approximately 0.2 to approximately 1.1 mmol/l at 8 h), or prevention of post-hypoglycaemic hyperketonaemia (plasma beta-hydroxybutyrate approximately 0.1 mmol/l throughout the study) after administration of acipimox, a potent inhibitor of lipolysis. In the latter study, glucose was infused to match the hypoglycaemia observed in the former study. The glycaemic thresholds and overall responses of counterregulatory hormones, symptoms (both autonomic and neuroglycopenic), and deterioration of cognitive function (psychomotor tests) were superimposable in the control study in which ketones increased spontaneously after onset of hypoglycaemic counterregulation, as compared to the study in which ketones were suppressed (p = NS). The fact that responses of counterregulatory hormones, symptoms and deterioration in cognitive function were not exaggerated when posthypoglycaemic hyperketonaemia was prevented, indicate that during hypoglycaemia, the counterregulatory-induced endogenous hyperketonaemia does not provide the human brain with an alternative substrate to glucose. Thus, it is concluded that during hypoglycaemia, endogenous hyperketonaemia does not contribute to brain metabolism and function.
Fanelli
C
C
Dipartimento di Medicina Interna e Scienze Endocrine e Metaboliche, Università di Perugia, Italy.
Di Vincenzo
A
A
Modarelli
F
F
Lepore
M
M
Ciofetta
M
M
Epifano
L
L
Pampanelli
S
S
Brunetti
P
P
Bolli
G B
GB
D020155:3-Hydroxybutyric Acid; D000328:Adult; D000409:Alanine / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D005260:Female; D005990:Glycerol / Q000097:blood; D006706:Homeostasis; D006728:Hormones / Q000097:blood; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007340:Insulinoma / Q000097:blood; D007657:Ketone Bodies / Q000097:blood*; D007773:Lactates / Q000097:blood; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D010190:Pancreatic Neoplasms / Q000097:blood; D011719:Pyrazines / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects
D006728:Hormones; D006885:Hydroxybutyrates; D000960:Hypolipidemic Agents; D007328:Insulin; D007657:Ketone Bodies; D007773:Lactates; D011719:Pyrazines; C027696:acipimox; D000409:Alanine; D005990:Glycerol; D020155:3-Hydroxybutyric Acid