Cholinergic involvement in vascular and glucoregulatory actions of insulin in rats.
This study was designed to test the glucose metabolic and vasodilator actions of insulin in rats and its relation to cholinergic system-dependent mechanisms. The first group of rats had pulsed Doppler flow probes and intravascular catheters implanted to determine blood pressure, heart rate, and regional blood flows. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp technique carried out in the absence or presence of atropine. The second group of rats was used to determine the cholinergic contribution to in vivo insulin-mediated glucose utilization in individual muscles. Glucose uptake was examined by using [(3)H]2-deoxy-D-glucose. Muscarinic cholinergic blockade was found to significantly (P = 0.002) reduce insulin sensitivity and to completely abrogate the renal (P = 0.008) and hindquarter (P = 0.02) vasodilator responses to euglycemic infusion of insulin. A significant reduction in insulin-stimulated in vivo glucose uptake was also noted in soleus (P = 0.006), quadriceps (P = 0.03), gastrocnemius (P = 0.02), and extensor digitorum longus (EDL) (P = 0.001) muscles, when insulin was infused at a rate of 4 mU . kg(-1) . min(-1), whereas at the rate of 16 mU . kg(-1) . min(-1), a significant reduction in glucose uptake was only observed in EDL (P = 0.03) and quadriceps (P = 0.01) muscles. Together, these results demonstrate a potential role for cholinergic involvement with physiological insulin actions in glucose clearance and blood flow regulation in rats.
Lévesque
Martin
M
Lipid Research Unit, Centre Hospitalier de l'Université Laval (CHUL) Research Center, Centre Hospitalier Universitaire de Québec (CHUQ), Ste-Foy, Canada.
Santuré
Marta
M
Pitre
Maryse
M
Nadeau
André
A
Bachelard
Hélène
H
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
D018678:Cholinergic Agents; D007328:Insulin; D001285:Atropine; D005947:Glucose