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- Title
Berberine Activates AMPK in L6 Myotubes by a Mechanism Other Than Via Changes in ATP Levels.
- Authors
Turner, Nigel; To, Sabrina; Gosby, Alison; Kraegen, Edward W.; James, David E.; Cooney, Gregory J.
- Abstract
The alkaloid drug berberine has recently been shown to exhibit beneficial effects in the treatment of obesity and type 2 diabetes, including reducing body weight, lowering blood lipids and improving insulin sensitivity. Although the exact mode a faction remains unclear, berberine appears to exert its favourable effects on glucose and lipid homeostasis in part through its ability to activate AMPK (AMP-activated protein kinase). As AMPK is a sensor of cellular energy status, we investigated whether berberine activates AMPK via inhibition of cellular respiration and a subsequent decrease in ATP concentration. Oxygen consumption in L6 myotubes and isolated mitochondria was measured using a Clark type oxygen electrode. Berberine inhibited oxygen consumption in a dose-dependent manner in L6 myotubes, with a maximum inhibition at 10 µM of approximately 50%. Interestingly, metformin also dose-dependently inhibited respiration in L6 cells, with an approximate 50% inhibition of respiration occurring at a concentration of 20 mM. In isolated muscle mitochondria, 10 µM berberine and 20 mM metformin had potent effects on complex I-linked respiration (malate + pyruvate), inhibiting oxygen consumption by approximately 60-75%. In contrast, complex II-linked respiration (succinate + rotenone) was not affected by berberine or metformin. ATP concentration was assessed in L6 myotubes by luciferase assay and despite significantly inhibiting respiration and increasing phosphorylation of AMPK, neither 10 µM berberine or 20 mM metformin reduced ATP levels. We conclude that similar to the antidiabetic drug metformin, berberine inhibits respiration in L6 myotubes and isolated muscle mitochondria. Despite this, berberine and metformin do not appear to activate AMPK via a mechanism involving a significant reduction in ATP levels.
- Subjects
BERBERINE; THERAPEUTIC use of alkaloids; OBESITY treatment; TYPE 2 diabetes; GLUCOSE; HOMEOSTASIS; PROTEIN kinases; PHOSPHORYLATION
- Publication
Diabetes, 2007, Vol 56, pA164
- ISSN
0012-1797
- Publication type
Academic Journal