Berberine improves free-fatty-acid-induced insulin resistance in L6 myotubes through inhibiting peroxisome proliferator-activated receptor gamma and fatty acid transferase expressions.
The plant alkaloid berberine (BBR) has been reported to have antidiabetic effect in humans and animals. However, the mechanism of action is not well understood. The present study was conducted to determine the effect and mechanism of action of BBR on the free-fatty-acid (FFA)-induced insulin resistance in muscle cells. The FFA-induced insulin-resistant cell model was established in L6 myotubes by treating them with 250 mumol/L of palmitic acid. The inclusion of FFA in the medium increased peroxisome proliferator-activated receptor gamma (PPARgamma) and fatty acid transferase (FAT/CD36) expressions by 26% and 50% and decreased glucose consumption by 43% and insulin-mediated glucose uptake by 63%, respectively. Berberine treatment increased the glucose consumption and insulin-stimulated glucose uptake in normal cells and improved glucose uptake in the FFA-induced insulin-resistant cells. The improved glucose uptake by BBR was accompanied with a dose-dependent decrease in PPARgamma and FAT/CD36 protein expressions. In insulin-resistant myotubes, BBR (5 micromol/L) decreased PPARgamma and FAT/CD36 proteins by 31% and 24%, whereas PPARgamma antagonist GW9662 reduced both proteins by 56% and 46%, respectively. In contrast, PPARgamma agonist rosiglitazone increased the expression of PPARgamma and FAT/CD36 by 34% and 21%, respectively. Our results suggest that BBR improves the FFA-induced insulin resistance in myotubes through inhibiting fatty acid uptake at least in part by reducing PPARgamma and FAT/CD36 expressions.
Chen
Yanfeng
Y
Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang 150081, China.
Li
Ying
Y
Wang
Yanwen
Y
Wen
Ying
Y
Sun
Changhao
C
D000813:Anilides / Q000494:pharmacology; D001599:Berberine / Q000494:pharmacology*; D015153:Blotting, Western; D018955:CD36 Antigens / Q000096:biosynthesis; D002334:Carnitine O-Palmitoyltransferase / Q000096:biosynthesis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D047493:PPAR alpha / Q000096:biosynthesis; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D018955:CD36 Antigens; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D001599:Berberine; D002334:Carnitine O-Palmitoyltransferase; D005947:Glucose