Insulin resistance induced by sucrose feeding in rats is due to an impairment of the hepatic parasympathetic nerves.
OBJECTIVE
A considerable proportion of whole-body insulin-stimulated glucose uptake is dependent upon the hepatic insulin-sensitising substance (HISS) in a pathway mediated by the hepatic parasympathetic nerves (HPNs). We tested the hypothesis that a high-sucrose diet leads to the impairment of the HPN-dependent component of insulin action.


METHODS
We quantified insulin sensitivity using the rapid insulin sensitivity test, a modified euglycaemic clamp. Quantification of the HPN-dependent component was achieved by administration of a muscarinic receptor antagonist (atropine, 3 mg/kg).


RESULTS
Insulin sensitivity was higher in standard-fed than in sucrose-fed Wistar rats (305.6+/-34.1 vs 193.9+/-13.7 mg glucose/kg body weight; p<0.005) and Sprague-Dawley rats (196.4+/-5.9 vs 95.5+/-16.3 mg glucose/kg body weight; p<0.01). The HPN-independent component was similar in the two diet groups. Insulin resistance was entirely due to an impairment of the HPN-dependent component in both Wistar rats (164.3+/-28.1 [standard-fed] vs 26.5+/-7.5 [sucrose-fed] mg glucose/kg body weight; p<0.0001) and Sprague-Dawley rats (111.7+/-9.5 vs 35.3+/-21.4 mg glucose/kg body weight; p<0.01). Furthermore, HPN-dependent insulin resistance in Sprague-Dawley rats was already evident after 2 weeks of a high-sucrose diet (28.5+/-7.6 [2 weeks], 35.3+/-21.4 [6 weeks], 17.9+/-5.4 [9 weeks] mg glucose/kg body weight) and was independent of the nature of sucrose supplementation (12.3+/-4.7 [solid] and 17.9+/-5.4 [liquid] mg glucose/kg body weight).


CONCLUSIONS
Our results support the hypothesis that insulin resistance caused by sucrose feeding is due to an impairment of the HPN-dependent component of insulin action, leading to a dysfunction of the HISS pathway.
Ribeiro
R T
RT
Department of Physiology, Faculty of Medical Sciences, New University of Lisbon, Campo Mártires da Pátria 130, 1169-056 Lisbon, Portugal.
Lautt
W W
WW
Legare
D J
DJ
Macedo
M P
MP
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D019422:Dietary Sucrose / Q000494:pharmacology*; D019587:Dietary Supplements; D007275:Injections, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D007700:Kinetics; D008099:Liver / Q000294:innervation*; D008297:Male; D051379:Mice; D023421:Models, Animal; D010275:Parasympathetic Nervous System / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D001786:Blood Glucose; D019422:Dietary Sucrose; D007328:Insulin; D001285:Atropine