Berberine Moderates Glucose and Lipid Metabolism through Multipathway Mechanism

Abstract

Berberine is known to improve glucose and lipid metabolism disorders, but the mechanism is still under investigation. In this paper, we explored the effects of berberine on the weight, glucose levels, lipid metabolism, and serum insulin of KKAy mice and investigated its possible glucose and lipid-regulating mechanism. We randomly divided KKAy mice into two groups: berberine group (treated with 250 mg/kg/d berberine) and control group. Fasting blood glucose (FBG), weight, total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), and fasting serum insulin were measured in both groups. The oral glucose tolerance test (OGTT) was performed. RT(2) PCR array gene expression analysis was performed using skeletal muscle of KKAy mice. Our data demonstrated that berberine significantly decreased FBG, area under the curve (AUC), fasting serum insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR) index, TC, and TG, compared with those of control group. RT(2) profiler PCR array analysis showed that berberine upregulated the expression of glucose transporter 4 (GLUT4), mitogen-activated protein kinase 14 (MAPK14), MAPK8(c-jun N-terminal kinase, JNK), peroxisome proliferator-activated receptor α (PPARα), uncoupling protein 2 (UCP2), and hepatic nuclear factor 4α(HNF4α), whereas it downregulated the expression of PPARγ, CCAAT/enhancer-binding protein (CEBP), PPARγ coactivator 1α(PGC 1α), and resistin. These results suggest that berberine moderates glucose and lipid metabolism through a multipathway mechanism that includes AMP-activated protein kinase-(AMPK-) p38 MAPK-GLUT4, JNK pathway, and PPARα pathway.

Figure 1

Weekly variation of body weight (a) and fasting blood glucose (b) between berberine group and control group. Data are expressed as means ± SD. *P < .05, **P < .01 compared with that in the control.

Figure 2

Comparison of plasma glucose concentration responses to an oral glucose tolerance test between berberine group and control group. Data are expressed as means ± SD. *P < .05, **P < .01 compared with that in the control.

Figure 3

Area under the curve in OGTT trial (a), serum concentration of fasting insulin (b), HOMA-IR, (c) and lipid metabolic parameters (d) between berberine group and control group. Data are expressed as means ± SD. *P < .05 compared with that in the control.

Figure 4

The Volcano Plot graphs of superarray. This graph shows that the log  2 of the fold change in each gene's expression between berberine group and control group is versus its P value from the t-test. The black line indicates fold changes of 1. The pink lines indicate that the fold change in gene expression threshold is 2. The blue line indicates that the P value of the t-test threshold is  .05. There were 10 genes which showed significantly different expression between berberine group and control group.

Figure 5

The mechanism of berberine moderating glucose and lipid metabolism.