**4.4 Regulation of glucose metabolism by HDL**

HDL may favorably regulate glucose metabolism. HDL promotes glycogen synthesis in skeletal muscle myocytes via SR-BI and stimulates glucose uptake by adipocytes [95]. HDL and apoA-I stimulate glucose uptake by skeletal muscle myocytes via increasing adenosine monophosphate-activated protein kinase (AMPK) activity [96]. HDL also enhances insulin secretion by pancreatic beta cells, which requires ABCA1-mediated cholesterol efflux as well as SR-BI expression [97]. In patients with type 2 diabetes mellitus (T2DM), intravenously injecting rHDL increases plasma insulin levels and decreases glucose concentrations *in vivo* [98].

### **4.5 HDL and cancer**

Epidemiological studies showed that CVD and cancer possess various similarities and possible interactions, including a number of common risk factors (e.g.,

smoking, obesity, and diabetes mellitus) and a shared biology [99]. Low HDL-C levels might be a prognostic factor for biliary tract cancer, prostate cancer, colon cancer, breast cancer, and gastric cancer [100, 101]. *In vitro* studies also demonstrated that native HDL could inhibit the migration and invasion of breast cancer cells [102, 103]. In addition, HDL could repress the adhesion of breast cancer cells to endothelial cells that mitigate the metastasis of breast cancer and reduce cancer growth through inhibiting tumor angiogenesis [104, 105].
