Glucose disposal by insulin, but not IGF-1, is dependent on the hepatic parasympathetic nerves.
Insulin-like growth factor-1 (IGF-1) has many insulin-like activities, including stimulation of glucose uptake in skeletal muscle. However, those with diabetes or chronic liver disease are insulin resistant but show a normal hypoglycemic response to IGF-1. We have previously shown that insulin sensitivity depends on a hepatic parasympathetic reflex release of a hormone from the liver. The hypothesis was tested that insulin action, but not IGF-1 action, is dependent on the hepatic parasympathetic reflex. Glucose disposal in response to three doses of IGF-1 (25, 100, 200 microg/kg) was determined in rats. IGF-1 at 200 microg/kg had similar effect on glucose disposal as did 50 mU/kg of insulin. Interruption of the hepatic parasympathetic reflex either by surgical ablation of the anterior nerve plexus or by atropine (1.0 mg/kg) resulted in insulin, but not IGF-1, resistance. Sixteen hours of fasting resulted in insulin, but not IGF-1, resistance. In conclusion, insulin, but not IGF-1, triggers the hepatic parasympathetic dependent release of a putative hepatic insulin sensitizing substance (HISS) that stimulates glucose uptake in skeletal muscle.
Sadri
P
P
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Lautt
W W
WW
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism*; D005215:Fasting / Q000097:blood; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D017777:Parasympathetic Fibers, Postganglionic / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000502:physiology*
D001786:Blood Glucose; D007328:Insulin; D018727:Muscarinic Antagonists; D007334:Insulin-Like Growth Factor I; D001285:Atropine