Inhibitory mechanism of caffeine on insulin-stimulated glucose uptake in adipose cells.
Caffeine inhibits insulin-induced glucose uptake in rat adipocytes and also decreases insulin sensitivity, including whole-body glucose disposal and glucose uptake in skeletal muscle, during a euglycemic-hyperinsulinemic clamp in human. However, the mechanism by which caffeine decreases the insulin sensitivity is not still clear. We found that pre-treatment with caffeine inhibited the insulin-induced 2-deoxy-D-[1-(3)H]glucose uptake in a concentration-dependent manner in mouse preadipose MC-3T3-G2/PA6 cells differentiated into mature adipose cells. Caffeine also suppressed insulin-induced GLUT4 translocation in the differentiated cells. Although caffeine did not alter insulin-induced activation of PI3K and protein kinase C-zeta (PKCzeta), an isoform of atypical PKC, which is reported to have an important role in insulin-induced GLUT4 translocation, we found that insulin-induced phosphorylation and activation of Akt were blocked by pre-treatment with caffeine. Inhibition of insulin-induced 2-deoxy-D-[1-(3)H]glucose uptake by caffeine was also observed in primary cultured brown adipocytes in a concentration-dependent manner. These results may, in part, explain the ability of caffeine to decrease insulin sensitivity.
Akiba Hospital, Chiba 289-1805, Japan.
Tetsuo
T
Akiba
Kuniko
K
Yaguchi
Kikue
K
Tsutsumi
Tatsuo
T
Nishioka
Ichiko
I
Koyama
Masaaki
M
Nomura
Koichi
K
Yokogawa
Shuzo
S
Moritani
Ken-ichi
K
Miyamoto
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002110:Caffeine / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D014316:Tritium; D000099221:Protein Kinase C zeta
D002110:Caffeine; D000242:Cyclic AMP; D003847:Deoxyglucose; D005947:Glucose; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D018047:Receptors, Purinergic P1; D014316:Tritium; D000099221:Protein Kinase C zeta