Daily physical activity enhances reactivity to insulin in skeletal muscle arterioles of hyperphagic Otsuka Long-Evans Tokushima Fatty rats.
Insulin-mediated glucose disposal is dependent on the vasodilator effects of insulin. In type 2 diabetes, insulin-stimulated vasodilation is impaired as a result of an imbalance in NO and ET-1 production. We tested the hypothesis that chronic voluntary wheel running (RUN) prevents impairments in insulin-stimulated vasodilation associated with obesity and type 2 diabetes independent of the effects of RUN on adiposity by randomizing Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of hyperphagia-induced obesity and type 2 diabetes, to 1) RUN, 2) caloric restriction (CR; diet adjusted to match body weights of RUN group), or 3) sedentary control (SED) groups (n = 8/group) at 4 wk. At 40 wk, NO- and ET-1-mediated vasoreactivity to insulin (1-1,000 μIU/ml) was assessed in the presence of a nonselective ET-1 receptor blocker (tezosentan) or a NO synthase (NOS) inhibitor [N(G)-nitro-L-arginine methyl ester (L-NAME)], respectively, in second-order arterioles isolated from the white portion of the gastrocnemius muscle. Body weight, fasting plasma glucose, and hemoglobin A1c were lower in RUN and CR than SED (P < 0.05); however, the glucose area under the curve (AUC) following the intraperitoneal glucose tolerance test was lower only in the RUN group (P < 0.05). Vasodilator responses to all doses of insulin were greater in RUN than SED or CR in the presence of a tezosentan (P < 0.05), but group differences in vasoreactivity to insulin with coadministration of L-NAME were not observed. We conclude daily wheel running prevents obesity and type 2 diabetes-associated declines in insulin-stimulated vasodilation in skeletal muscle arterioles through mechanisms that appear to be NO mediated and independent of attenuating excess adiposity in hyperphagic rats.
Mikus
Catherine R
CR
Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, USA.
Rector
R Scott
RS
Arce-Esquivel
Arturo A
AA
Libla
Jessica L
JL
Booth
Frank W
FW
Ibdah
Jamal A
JA
Laughlin
M Harold
MH
Thyfault
John P
JP
D050154:Adiposity; D000818:Animals; D001160:Arterioles / Q000378:metabolism / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D001835:Body Weight; D031204:Caloric Restriction; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004435:Eating; D019332:Endothelin-1 / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006963:Hyperphagia / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000098:blood supply*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D010766:Phosphorylation; D051381:Rats; D020334:Rats, Inbred OLETF; D012420:Running; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D001786:Blood Glucose; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D007328:Insulin; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat