Short-term AMP-regulated protein kinase activation enhances insulin-sensitive fatty acid uptake and increases the effects of insulin on fatty acid oxidation in L6 muscle cells.
Evidence shows that exercise increases insulin-sensitive glucose uptake and that exercise-induced AMP-regulated protein kinase (AMPK) activation is a likely candidate to mediate this metabolic adaptation. The purpose of this study was to determine whether repeated AMPK activation can similarly enhance insulin-sensitive fatty acid (FA) metabolism. L6 myotubes were incubated under the following conditions: repeated plus acute 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) treatment (RAA; 1 mmol/L AICAR for 5 h/d for 5 days plus 1 mmol/L AICAR for 60 min on day 6), repeated AICAR (RA; 1 mmol/L AICAR for 5 h/d for five days) or acute AICAR (AA; 1 mmol/L AICAR for 60 min) and were compared with control cells that were not treated with AICAR. On day six, cells from each group were incubated with or without 100 nmol/L insulin. AICAR treatment and insulin stimulation independently increased (P < 0.05) palmitate uptake in all groups. RAA potentiated the insulin-induced increase in palmitate uptake by 97% (P < 0.05) as compared with control cells. RA and AA treatments prevented the insulin-induced decrease in palmitate oxidation, while RAA treatment restored the sensitivity of the cells to insulin action on palmitate oxidation. Total peroxisome proliferator-activated receptor-gamma co-activator-1 alpha, atypical protein kinase C-zeta, cytochrome C and CD36 protein content was increased (P < 0.05) by RA treatment, but unaffected by insulin. These results indicate that repeated AMPK activation induces improvements in insulin-sensitive FA uptake and oxidation and that this occurs partly via changes in the expression of proteins linked to insulin signaling and FA uptake and oxidation capacity.
Kelly
Karen R
KR
Department of Kinesiology, College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089-0652, USA.
Abbott
Marcia J
MJ
Turcotte
Lorraine P
LP
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology
D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D010168:Palmitates; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide