Long-term high density lipoprotein infusion ameliorates metabolic phenotypes of diabetic db/db mice

Lower quantity and quality of high density lipoprotein (HDL) are important characteristics of type 2 diabetes mellitus. Acute HDL infusion results in a greater fall of plasma glucose in diabetes patients. Here, we aim to investigate the influence of long-term HDL infusion on metabolic phenotypes of diabetic db/db mice.

High density lipoprotein was introduced to db/db mice twice a week for 4 weeks. The phenotypes of the mice were monitored by analyzing metabolic parameters. Glycogen analysis was performed with amyloglucosidase. The corresponding signaling molecules were detected by western blot.

Long-term introduction of HDL decreased plasma glucose levels of db/db mice. Glycogen deposition was enhanced in gastrocnemius muscle, paralleling the elevated glycogen synthase kinase-3 phosphorylation. Meanwhile, increased Akt-Ser473 and adenosine monophosphate-activated protein kinase phosphorylations were detected in the muscle. Moreover, HDL reduced blood glucose and free fatty acids and improved pancreatic islet structure and function with increased C-peptide. Furthermore, decreased interleukin-6, C-reactive protein, monocyte chemoattractant protein-1, resistin, and malondialdehyde, as well as enhanced leptin levels were detected in HDL-treated mice.

Results of the present study suggest that long-term HDL infusion has positive therapeutic effects on the metabolic disturbances of db/db diabetic mice.