5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men

Daniel J. Cuthbertson, John A. Babraj, Kirsteen J.W. Mustard, Mhairi C. Towler, Kevin A. Green, Henning Wackerhage, Graeme P. Leese, Keith Barr, Michaela Thomason-Hughes, Calum Sutherland, D. Graeme Hardie, Michael J. Rennie

Research output: Contribution to journalArticle

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Abstract

Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), and adiponectin increases glucose uptake. The aim of this study was to determine whether AICAR stimulates muscle glucose uptake in humans. We studied 29 healthy men (aged 26 ± 8 years, BMI 25 ± 4 kg/m2 [mean ± SD]). Rates of muscle 2-deoxyglucose (2DG) uptake were determined by measuring accumulation of total muscle 2DG (2DG and 2DG-6-phosphate) during a primed, continuous 2DG infusion. The effects of AICAR and exercise on muscle AMPK activity/phosphorylation and 2DG uptake were determined. Whole-body glucose disposal was compared before and during AICAR with the euglycemic-hyperinsulinemic clamp. Muscle 2DG uptake was linear over 9 h (R2 = 0.88 ± 0.09). After 3 h, 2DG uptake increased 2.1 ± 0.8- and 4.7 ± 1.7-fold in response to AICAR or bicycle exercise, respectively. AMPK α1 and α2 activity or AMPK phosphorylation was unchanged after 20 min or 3 h of AICAR, but AMPK phosphorylation significantly increased immediately and 3 h after bicycle exercise. AICAR significantly increased phosphorylation of extracellular signal-regulated kinase 1/2, but phosphorylation of β-acetyl-CoA carboxylase, glycogen synthase, and protein kinase B or insulin receptor substrate-1 level was unchanged. Mean whole-body glucose disposal increased by 7% with AICAR from 9.3 ± 0.6 to 10 ± 0.6 mg x kg-1 x min-1 (P < 0.05). In healthy people, AICAR acutely stimulates muscle 2DG uptake with a minor effect on whole-body glucose disposal.
Original languageEnglish
Pages (from-to)2078-2084
Number of pages7
JournalDiabetes
Volume56
Issue number8
Early online date18 May 2007
DOIs
Publication statusPublished - Aug 2007
Externally publishedYes

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Aminoimidazole Carboxamide
Deoxyglucose
Skeletal Muscle
AMP-Activated Protein Kinases
Muscles
Phosphorylation
Glucose
Exercise
Acetyl-CoA Carboxylase
4-aminoimidazole
Glycogen Synthase Kinases
Insulin Receptor Substrate Proteins
Proto-Oncogene Proteins c-akt
Glucose Clamp Technique
Mitogen-Activated Protein Kinase 3
Metformin
Mitogen-Activated Protein Kinase 1
Adiponectin
Rodentia

Cite this

Cuthbertson, D. J., Babraj, J. A., Mustard, K. J. W., Towler, M. C., Green, K. A., Wackerhage, H., ... Rennie, M. J. (2007). 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. Diabetes, 56(8), 2078-2084. https://doi.org/10.2337/db06-1716
Cuthbertson, Daniel J. ; Babraj, John A. ; Mustard, Kirsteen J.W. ; Towler, Mhairi C. ; Green, Kevin A. ; Wackerhage, Henning ; Leese, Graeme P. ; Barr, Keith ; Thomason-Hughes, Michaela ; Sutherland, Calum ; Hardie, D. Graeme ; Rennie, Michael J. / 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. In: Diabetes. 2007 ; Vol. 56, No. 8. pp. 2078-2084.
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abstract = "Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), and adiponectin increases glucose uptake. The aim of this study was to determine whether AICAR stimulates muscle glucose uptake in humans. We studied 29 healthy men (aged 26 ± 8 years, BMI 25 ± 4 kg/m2 [mean ± SD]). Rates of muscle 2-deoxyglucose (2DG) uptake were determined by measuring accumulation of total muscle 2DG (2DG and 2DG-6-phosphate) during a primed, continuous 2DG infusion. The effects of AICAR and exercise on muscle AMPK activity/phosphorylation and 2DG uptake were determined. Whole-body glucose disposal was compared before and during AICAR with the euglycemic-hyperinsulinemic clamp. Muscle 2DG uptake was linear over 9 h (R2 = 0.88 ± 0.09). After 3 h, 2DG uptake increased 2.1 ± 0.8- and 4.7 ± 1.7-fold in response to AICAR or bicycle exercise, respectively. AMPK α1 and α2 activity or AMPK phosphorylation was unchanged after 20 min or 3 h of AICAR, but AMPK phosphorylation significantly increased immediately and 3 h after bicycle exercise. AICAR significantly increased phosphorylation of extracellular signal-regulated kinase 1/2, but phosphorylation of β-acetyl-CoA carboxylase, glycogen synthase, and protein kinase B or insulin receptor substrate-1 level was unchanged. Mean whole-body glucose disposal increased by 7{\%} with AICAR from 9.3 ± 0.6 to 10 ± 0.6 mg x kg-1 x min-1 (P < 0.05). In healthy people, AICAR acutely stimulates muscle 2DG uptake with a minor effect on whole-body glucose disposal.",
author = "Cuthbertson, {Daniel J.} and Babraj, {John A.} and Mustard, {Kirsteen J.W.} and Towler, {Mhairi C.} and Green, {Kevin A.} and Henning Wackerhage and Leese, {Graeme P.} and Keith Barr and Michaela Thomason-Hughes and Calum Sutherland and Hardie, {D. Graeme} and Rennie, {Michael J.}",
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Cuthbertson, DJ, Babraj, JA, Mustard, KJW, Towler, MC, Green, KA, Wackerhage, H, Leese, GP, Barr, K, Thomason-Hughes, M, Sutherland, C, Hardie, DG & Rennie, MJ 2007, '5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men', Diabetes, vol. 56, no. 8, pp. 2078-2084. https://doi.org/10.2337/db06-1716

5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. / Cuthbertson, Daniel J.; Babraj, John A.; Mustard, Kirsteen J.W.; Towler, Mhairi C.; Green, Kevin A.; Wackerhage, Henning; Leese, Graeme P.; Barr, Keith; Thomason-Hughes, Michaela; Sutherland, Calum; Hardie, D. Graeme; Rennie, Michael J.

In: Diabetes, Vol. 56, No. 8, 08.2007, p. 2078-2084.

Research output: Contribution to journalArticle

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T1 - 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men

AU - Cuthbertson, Daniel J.

AU - Babraj, John A.

AU - Mustard, Kirsteen J.W.

AU - Towler, Mhairi C.

AU - Green, Kevin A.

AU - Wackerhage, Henning

AU - Leese, Graeme P.

AU - Barr, Keith

AU - Thomason-Hughes, Michaela

AU - Sutherland, Calum

AU - Hardie, D. Graeme

AU - Rennie, Michael J.

PY - 2007/8

Y1 - 2007/8

N2 - Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), and adiponectin increases glucose uptake. The aim of this study was to determine whether AICAR stimulates muscle glucose uptake in humans. We studied 29 healthy men (aged 26 ± 8 years, BMI 25 ± 4 kg/m2 [mean ± SD]). Rates of muscle 2-deoxyglucose (2DG) uptake were determined by measuring accumulation of total muscle 2DG (2DG and 2DG-6-phosphate) during a primed, continuous 2DG infusion. The effects of AICAR and exercise on muscle AMPK activity/phosphorylation and 2DG uptake were determined. Whole-body glucose disposal was compared before and during AICAR with the euglycemic-hyperinsulinemic clamp. Muscle 2DG uptake was linear over 9 h (R2 = 0.88 ± 0.09). After 3 h, 2DG uptake increased 2.1 ± 0.8- and 4.7 ± 1.7-fold in response to AICAR or bicycle exercise, respectively. AMPK α1 and α2 activity or AMPK phosphorylation was unchanged after 20 min or 3 h of AICAR, but AMPK phosphorylation significantly increased immediately and 3 h after bicycle exercise. AICAR significantly increased phosphorylation of extracellular signal-regulated kinase 1/2, but phosphorylation of β-acetyl-CoA carboxylase, glycogen synthase, and protein kinase B or insulin receptor substrate-1 level was unchanged. Mean whole-body glucose disposal increased by 7% with AICAR from 9.3 ± 0.6 to 10 ± 0.6 mg x kg-1 x min-1 (P < 0.05). In healthy people, AICAR acutely stimulates muscle 2DG uptake with a minor effect on whole-body glucose disposal.

AB - Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), and adiponectin increases glucose uptake. The aim of this study was to determine whether AICAR stimulates muscle glucose uptake in humans. We studied 29 healthy men (aged 26 ± 8 years, BMI 25 ± 4 kg/m2 [mean ± SD]). Rates of muscle 2-deoxyglucose (2DG) uptake were determined by measuring accumulation of total muscle 2DG (2DG and 2DG-6-phosphate) during a primed, continuous 2DG infusion. The effects of AICAR and exercise on muscle AMPK activity/phosphorylation and 2DG uptake were determined. Whole-body glucose disposal was compared before and during AICAR with the euglycemic-hyperinsulinemic clamp. Muscle 2DG uptake was linear over 9 h (R2 = 0.88 ± 0.09). After 3 h, 2DG uptake increased 2.1 ± 0.8- and 4.7 ± 1.7-fold in response to AICAR or bicycle exercise, respectively. AMPK α1 and α2 activity or AMPK phosphorylation was unchanged after 20 min or 3 h of AICAR, but AMPK phosphorylation significantly increased immediately and 3 h after bicycle exercise. AICAR significantly increased phosphorylation of extracellular signal-regulated kinase 1/2, but phosphorylation of β-acetyl-CoA carboxylase, glycogen synthase, and protein kinase B or insulin receptor substrate-1 level was unchanged. Mean whole-body glucose disposal increased by 7% with AICAR from 9.3 ± 0.6 to 10 ± 0.6 mg x kg-1 x min-1 (P < 0.05). In healthy people, AICAR acutely stimulates muscle 2DG uptake with a minor effect on whole-body glucose disposal.

U2 - 10.2337/db06-1716

DO - 10.2337/db06-1716

M3 - Article

VL - 56

SP - 2078

EP - 2084

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 8

ER -