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  • Disclosing caffeine action on insulin sensitivity: effects on rat skeletal muscle.

Disclosing caffeine action on insulin sensitivity: effects on rat skeletal muscle.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (2015-02-11)
Joana F Sacramento, Maria J Ribeiro, Sara Yubero, Bernardete F Melo, Ana Obeso, Maria P Guarino, Constancio Gonzalez, Silvia V Conde
ABSTRACT

Caffeine, a non-selective adenosine antagonist, has distinct effects on insulin sensitivity when applied acutely or chronically. Herein, we investigated the involvement of adenosine receptors on insulin resistance induced by single-dose caffeine administration. Additionally, the mechanism behind adenosine receptor-mediated caffeine effects in skeletal muscle was assessed. The effect of the administration of caffeine, 8-cycle-1,3-dipropylxanthine (DPCPX, A1 antagonist), 2-(2-Furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine (SCH58261, A2A antagonist) and 8-(4-{[(4-cyanophenyl)carbamoylmethyl]-oxy}phenyl)-1,3-di(n-propyl)xanthine (MRS1754, A2B antagonist) on whole-body insulin sensitivity was tested. Skeletal muscle Glut4,5'-AMP activated protein kinase (AMPK) and adenosine receptor protein expression were also assessed. The effect of A1 and A2B adenosine agonists on skeletal muscle glucose uptake was evaluated in vitro. Sodium nitroprussiate (SNP, 10nM), a nitric oxide (NO) donor, was used to evaluate the effect of NO on insulin resistance induced by adenosine antagonists. Acute caffeine decreased insulin sensitivity in a concentration dependent manner (Emax=55.54±5.37%, IC50=11.61nM), an effect that was mediated by A1 and A2B adenosine receptors. Additionally, acute caffeine administration significantly decreased Glut4, but not AMPK expression, in skeletal muscle. We found that A1, but not A2B agonists increased glucose uptake in skeletal muscle. SNP partially reversed DPCPX and MRS1754 induced-insulin resistance. Our results suggest that insulin resistance induced by acute caffeine administration is mediated by A1 and A2B adenosine receptors. Both Glut4 and NO seem to be downstream effectors involved in insulin resistance induced by acute caffeine.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Acetamide, sublimed, 99%
Sigma-Aldrich
Acetamide, ≥99.0% (GC)
Sigma-Aldrich
8-Cyclopentyl-1,3-dipropylxanthine, solid
Sigma-Aldrich
Bicinchoninic acid disodium salt hydrate, ≥98% (HPLC)
Sigma-Aldrich
Acetamide, ~99% (GC)
Sigma-Aldrich
(3-Aminopropyl)triethoxysilane, packaged for use in deposition systems, ≥98%
Adenosine, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
(3-Aminopropyl)triethoxysilane, ≥98.0%
Sigma-Aldrich
(3-Aminopropyl)triethoxysilane, 99%
Sigma-Aldrich
Adenosine
Sigma-Aldrich
Adenosine, ≥99%
Sigma-Aldrich
DAPI, for nucleic acid staining
Sigma-Aldrich
Adenosine, suitable for cell culture, BioReagent
Sigma-Aldrich
N6-Cyclopentyladenosine, solid
Sigma-Aldrich
(3-Aminopropyl)triethoxysilane, ≥98%
Supelco
Adenosine, Pharmaceutical Secondary Standard; Certified Reference Material