Disclosing caffeine action on insulin sensitivity: Effects on rat skeletal muscle

作者：Sacramento Joana F; Ribeiro Maria J; Yubero Sara; Melo Bernardete F; Obeso Ana; Guarino Maria P; Gonzalez Constancio; Conde Silvia V^*

来源：European Journal of Pharmaceutical Sciences, 2015, 70: 107-116.

DOI：10.1016/j.ejps.2015.01.011

• Adenosine receptors
• Caffeine
• Insulin resistance
• Glut4
• Nitric oxide

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, A(1) antagonist), 2-(2-Furanyl)-7-(2-phenylethyl)-7H-pyrazolo [4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine (SCH58261, A(2A) antagonist) and 8-(4-([(4-cyanophenyl)carbamoylmethyl]-oxy}phenyl)-1,3-di(n-propyl)xanthine (MRS1754, A(2B) 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 A(1) and A(2B) adenosine agonists on skeletal muscle glucose uptake was evaluated in vitro. Sodium nitroprussiate (SNP, 10 nM), 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 (E-max = 55.54 +/- 5.37%, IC50 = 11.61 nM), an effect that was mediated by A(1) and A(2B) adenosine receptors. Additionally, acute caffeine administration significantly decreased Glut4, but not AMPK expression, in skeletal muscle. We found that A(1), but not A(2B) 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 A(1) and A(2B) adenosine receptors. Both Glut4 and NO seem to be downstream effectors involved in insulin resistance induced by acute caffeine.

• 出版日期2015-4-5