The role of hepatic portal glucose sensing in modulating responses to hypoglycaemia in man.
OBJECTIVE
The role of glucose sensing cells in the human hepatic portal system in the initiation of the neuroendocrine responses to acute hypoglycaemia is not known. We investigated the effect of raising blood glucose concentrations in the hepatic-portal vein on neurohumoral responses during induction of systemic hypoglycaemia in nine healthy male volunteers.


METHODS
Each subject received an insulin infusion (3 mU.kg(-1).min(-1)) on two occasions, in random order. Variable rate glucose infusion was used to maintain plasma glucose at 5 mmol/l for 60 min, then 3.2 mmol/l for 60 min. At 20 min prior to hypoglycaemia, subjects drank 20 g of glucose in water or water sweetened with saccharin. In five of the volunteers, the oral glucose was labelled with U-13C6 glucose, which showed peak systemic glucose absorption between 90 and 110 min. Five volunteers also repeated the study with a euglycaemic clamp.


RESULTS
Oral glucose was associated with a reduction in the early adrenaline response to hypoglycaemia, the area under the curve from 90 to 110 min falling from 24.02+/-20.84 (means +/- SD) to 15.26+/-13.65 nmol/l per 20 min, p<0.05. Symptom scores (area under curve) decreased from 99.72+/-91.86 to 16.39+/-94.71, p=0.008 (total), 51.8+/-68.61 to 7.78+/-41.61, p=0.03 (autonomic) and 54.17+/-50.61 to 8.6+/-57.99 with oral glucose, p=0.001 (neuroglycopenic). Oral glucose did not influence symptoms during euglycaemia.


CONCLUSIONS
Our data are compatible with the hypothesis that centrally mediated symptomatic and neuroendocrine responses are attenuated by glucose detection in the hepatic portal vein in humans.
Smith
D
D
Department of Diabetes, Guy's Kings and St Thomas', King's College School of Medicine, Denmark Hill Campus, Bessemer Road, London SE5 9PJ, UK.
Pernet
A
A
Reid
H
H
Bingham
E
E
Rosenthal
J M
JM
Macdonald
I A
IA
Umpleby
A M
AM
Amiel
S A
SA
D000222:Adaptation, Physiological; D000328:Adult; D001786:Blood Glucose / Q000502:physiology*; D004837:Epinephrine / Q000097:blood / Q000378:metabolism; D015309:Glucose Clamp Technique; D006706:Homeostasis; D006801:Humans; D007003:Hypoglycemia / Q000097:blood* / Q000503:physiopathology; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D011168:Portal System / Q000502:physiology*; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D009638:Norepinephrine; D004837:Epinephrine