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Insulin‐Mediated Vasodilation in Cerebral Arteries is Impaired in Obese Rats with Type 2 Diabetes
Author(s) -
Olver T. Dylan,
McDonald Matt W,
Klakotskaia Diana,
Richardson Rachel A,
Jasperse Jeffrey A,
Yang Hsiao T,
Thorne Pam K,
Melling C.W. James,
Schactman Todd R.,
Emter Craig A,
Laughlin M. Harold
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1203.5
Subject(s) - medicine , endocrinology , electrical impedance myography , vasodilation , insulin resistance , type 2 diabetes , insulin , cerebral arteries , blood pressure , vasomotor , diabetes mellitus
Insulin stimulates resistance artery vasodilation in skeletal muscle and the brain. Type 2 diabetes (T2D) attenuates insulin‐induced vasodilation in skeletal muscle arteries, but whether this adaptation occurs in the cerebrovasculature and is related to impaired cognition remains to be elucidated. This study tested the hypothesis that cognition and insulin‐mediated vasodilation in the cerebrovasculature were impaired in obese rats with type 2 diabetes. Eight week old hyperphagic, Otsuka Long Evans Tokushima Fatty rats were divided into two groups; food controlled (CON, n=8) and free food access (model of T2D, n=8). Cognition was measured monthly using a Barnes maze for 4 months (i.e. at 8, 12, 16 and 20 wk of age) prior to vascular testing. At 20 wk of age, rats underwent a euglycemic hyperinsulinemic clamp, while carotid artery blood flow (BF; perivascular flow probe) and mean arterial pressure (MAP; arterial catheter) were measured. Thereafter, rats were decapitated, their cerebral arteries were isolated, and vasomotor responses (pressurized myography) to graded increases in intraluminal pressure (40–140 mmHg) and exogenous insulin (1–10000 uIU) were assessed in untreated and endothelin‐1 inhibition (BQ123) conditions. Results indicate that cognition improved over time, but was not different between groups at any time point. Carotid BF, MAP and vascular conductance (BF/MAP) were also not different between groups and did not change during the insulin clamp. Prior to and following the development of spontaneous tone, absolute diameter of the cerebral arteries was not different between groups. Vasomotor tone increased similarly in both groups during graded increases in intraluminal pressure (40–140 mmHg; P<0.05). Insulin‐mediated vasodilation (at 80 mmHg pressure) was attenuated in the T2D vs. CON (peak dilation = ~10 % vs. 30%; P<0.05). Endothelin‐1 inhibition restored insulin‐mediated vasodilation in the T2D group. A priori pairwise comparison between the cumulative average percent possible insulin‐mediated vasodilation in the untreated vs. endothelin‐1 inhibition conditions revealed that endothelin‐1 significantly restrained insulin‐mediated vasodilation in the T2D, but not the CON group (P<0.05). Thus, at this stage in development of T2D (~20 wk is the onset in this model), cognition, and cranial flow at rest and during an insulin clamp appear unaffected; even though isolated cerebral arteries exhibit vascular insulin resistance. These data from isolated cerebral arteries support the notion that impaired insulin‐mediated cerebral vasodilation in T2D is the result of enhanced insulin‐stimulated endothelin‐1 production. Support or Funding Information College of Veterinary Medicine, University of Missouri‐Columbia