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Enhancement of insulin-mediated rat muscle glucose uptake and microvascular perfusion by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside

Bradley, Eloise A., Zhang, Lei, Genders, Amanda J., Richards, Stephen M., Rattigan, Stephen and Keske, Michelle A. 2015, Enhancement of insulin-mediated rat muscle glucose uptake and microvascular perfusion by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, Cardiovascular diabetology, vol. 14, pp. 1-12, doi: 10.1186/s12933-015-0251-y.

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Title Enhancement of insulin-mediated rat muscle glucose uptake and microvascular perfusion by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside
Author(s) Bradley, Eloise A.
Zhang, Lei
Genders, Amanda J.
Richards, Stephen M.
Rattigan, Stephen
Keske, Michelle A.ORCID iD for Keske, Michelle A. orcid.org/0000-0003-4214-7628
Journal name Cardiovascular diabetology
Volume number 14
Article ID 91
Start page 1
End page 12
Total pages 12
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2015-07-22
ISSN 1475-2840
Keyword(s) Aminoimidazole Carboxamide
Animals
Blood Flow Velocity
Contrast Media
Deoxyglucose
Femoral Artery
Glucose Clamp Technique
Hindlimb
Hypoglycemic Agents
Insulin
Lactic Acid
Male
Microbubbles
Microcirculation
Microvessels
Muscle Fibers, Fast-Twitch
Muscle Fibers, Slow-Twitch
Muscle, Skeletal
Nitric Oxide Synthase
Rats, Wistar
Regional Blood Flow
Ribonucleotides
Time Factors
Ultrasonography
Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Endocrinology & Metabolism
Cardiovascular System & Cardiology
Muscle
Glucose
Summary BACKGROUND: Insulin-induced microvascular recruitment is important for optimal muscle glucose uptake. 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR, an activator of AMP-activated protein kinase), can also induce microvascular recruitment, at doses that do not acutely activate glucose transport in rat muscle. Whether low doses of AICAR can augment physiologic insulin action is unknown. In the present study we used the euglycemic hyperinsulinemic clamp to assess whether insulin action is augmented by low dose AICAR. METHODS: Anesthetized rats were studied during saline infusion or euglycemic insulin (3 mU/kg/min) clamp for 2 h in the absence or presence of AICAR for the last hour (5 mg bolus followed by 3.75 mg/kg/min). Muscle glucose uptake (R'g) was determined radioisotopically with (14)C-2-deoxyglucose and muscle microvascular perfusion by contrast-enhanced ultrasound with microbubbles. RESULTS: AICAR did not affect blood glucose, or lower leg R'g, although it significantly (p < 0.05) increased blood lactate levels and augmented muscle microvascular blood volume via a nitric oxide synthase dependent pathway. Insulin increased femoral blood flow, whole body glucose infusion rate (GIR), R'g, hindleg glucose uptake, and microvascular blood volume. Addition of AICAR during insulin infusion increased lactate production, further increased R'g in Type IIA (fast twitch oxidative) and IIB (fast twitch glycolytic) fiber containing muscles, and hindleg glucose uptake, but decreased R'g in the Type I (slow twitch oxidative) fiber muscle. AICAR also decreased GIR due to inhibition of insulin-mediated suppression of hepatic glucose output. AICAR augmented insulin-mediated microvascular perfusion. CONCLUSIONS: AICAR, at levels that have no direct effect on muscle glucose uptake, augments insulin-mediated microvascular blood flow and glucose uptake in white fiber type muscles. Agents targeted to endothelial AMPK activation are promising insulin sensitizers, however, the decrease in GIR and the propensity to increase blood lactate cautions against AICAR as an acute insulin sensitizer.
Language eng
DOI 10.1186/s12933-015-0251-y
Field of Research 110299 Cardiorespiratory Medicine and Haematology not elsewhere classified
110306 Endocrinology
1102 Cardiovascular Medicine And Haematology
Socio Economic Objective 920103 Cardiovascular System and Diseases
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Grant ID NHMRC 1043474
ARC DP0877385
Copyright notice ©2015, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30092191

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.