Berberine acutely activates the glucose transport activity of GLUT1

Abstract

Berberine, which has a long history of use in Chinese medicine, has recently been shown to have efficacy in the treatment of diabetes. While the hypoglycemic effect of berberine has been clearly documented in animal and cell line models, such as 3T3-L1 adipocytes and L6 myotube cells, the mechanism of action appears complex with data implicating activation of the insulin signaling pathway as well as activation of the exercise or AMP kinase-mediated pathway. There have been no reports of the acute affects of berberine on the transport activity of the insulin-insensitive glucose transporter, GLUT1. Therefore, we examined the acute effects of berberine on glucose uptake in L929 fibroblast cells, a cell line that express only GLUT1. Berberine activated glucose uptake reaching maximum stimulation of five fold at >40 μM. Significant activation (P<0.05) was measured within five minutes reaching a maximum by 30 minutes. The berberine effect was not additive to the maximal stimulation by other known stimulants, azide, methylene blue or glucose deprivation, suggesting shared steps between berberine and these stimulants. Berberine significantly reduced the Km of glucose uptake from 6.7 ± 1.9 mM to 0.55 ± 0.08 mM, but had no effect on the Vmax of uptake. Compound C, an inhibitor of AMP kinase, did not affect berberine-stimulated glucose uptake, but inhibitors of downstream kinases partially blocked berberine stimulation. SB203580 (inhibitor of p38 MAP kinase) did not affect submaximal berberine activation, but did lower maximal berberine stimulation by 26%, while PD98059 (inhibitor of ERK kinase) completely blocked submaximal berberine activation and decreased the maximal stimulation by 55%. It appears from this study that a portion of the hypoglycemic effects of berberine can be attributed to its acute activation of the transport activity of GLUT1.

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“…Cardioprotective Regulated AMP-activated protein kinase activity in heart [99] . Hypoglycemic Activated the transport activity of glucose transporter 1 (GLUT1) [100] .…”

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“…It is noteworthy that the mechanism of action of berberine may affect several important metabolic pathways, e.g. reducing cholesterol and other triglycerides but also influencing glucose metabolism and reducing the HbA1c level [250][251][252]. The antimicrobial activity of berberine that changes the bacterial flora in the gastrointestinal tract [253] may inspire its further application in pharma treatment.…”

Deciphering the therapeutic mechanisms of Xiao-Ke-An in treatment of type 2 diabetes in mice by a Fangjiomics approach

“…In this study, XKA reversed the decreased mRNA expression of the insulin receptor (INSR), which might be attributed to the effect of berberine. Additionally, a portion of the hypoglycemic effects of berberine might be attributed to its improvement of glucose transport [25,26] . XKA reversed the decreased mRNA expression of solute carrier family 2 member 1 (SLC2A1), which might contribute to this effect of XKA.…”