Lysophosphatidylcholine Activates Adipocyte Glucose Uptake and Lowers Blood Glucose Levels in Murine Models of Diabetes

Abstract

Glucose homeostasis is maintained by the orchestration of peripheral glucose utilization and hepatic glucose production, mainly by insulin. In this study, we found by utilizing a combined parallel chromatography mass profiling approach that lysophosphatidylcholine (LPC) regulates glucose levels. LPC was found to stimulate glucose uptake in 3T3-L1 adipocytes dose-and time-dependently, and this activity was found to be sensitive to variations in acyl chain lengths and to polar head group types in LPC. Treatment with LPC resulted in a significant increase in the level of GLUT4 at the plasma membranes of 3T3-L1 adipocytes. Moreover, LPC did not affect IRS-1 and AKT2 phosphorylations, and LPC-induced glucose uptake was not influenced by pretreatment with the PI 3-kinase inhibitor LY294002. However, glucose uptake stimulation by LPC was abrogated both by rottlerin (a protein kinase C␦ inhibitor) and by the adenoviral expression of dominant negative protein kinase C␦. In line with its determined cellular functions, LPC was found to lower blood glucose levels in normal mice. Furthermore, LPC improved blood glucose levels in mouse models of type 1 and 2 diabetes. These results suggest that an understanding of the mode of action of LPC may provide a new perspective of glucose homeostasis.

Metabolomics reveal 1-palmitoyl lysophosphatidylcholine production by peroxisome proliferator-activated receptor α

“…1A ; supplementary Table 1). A previous study reported that LPC(16:0) increased adipocyte glucose uptake ( 31 ). We confi rmed that plasma glucose was decreased (to ‫ف‬ 60% vs. control) by bezafi brate treatment ( Table 1 ).…”

“…It is well recognized that LPC(16:0) increases adipocyte glucose uptake ( 31 ). We also confi rmed the LPC(16:0) capacity to promote glucose uptake in 3T3-L1 adipocytes in a dose-dependent manner and LPC(16:0) had an additive effect increasing glucose uptake in 3T3-L1 adipocytes cotreated with insulin and LPC(16:0) (data not shown).…”

“…1A-D). In the MS/MS data, we confi rmed the fragment ion ( m/z 184), which has been reported to be characteristic of LPC ( 31,32 ). We also quantifi ed plasma LPC(16:0) and showed that plasma LPC(16:0) was increased by bezafibrate treatment (control group: 192.45 ± 12.85 µM; bezafibrate: 437.16 ± 29.63 µM; P < 0.001; Fig.…”

Structural Elucidation of a Novel Polysaccharide from Pseudostellaria heterophylla and Stimulating Glucose Uptake in Cells and Distributing in Rats by Oral

“…For example, the activation of α 1 -adrenergic or endothelin A receptors results in enhanced glucose uptake rates independently of insulin levels, and physical exercise also plays an important role in the metabolism of glucose by skeletal muscle. Hence, exercise or drug-mediated glucose uptake, are therapeutic targets in type 2 diabetes [12,13].…”

Investigation into the mechanisms of beta-cell specific overexpression of peroxisome proliferator activated receptors in obesity-induced type 2 diabetes.

“…In adipose tissue, it has been shown that increases in specific LysoPC species 12:0, 16:0, and 18:0 caused an increase in the glucose 4 transporter and therefore increased glucose uptake in a dose dependant manner (Yea et al, 2009). These findings provide another example o f how changes in lipid profiles o f adipose tissue could result in impaired glucose uptake and therefore lead to hyperglycemia in patients with T2D.…”