Table 1.
Role of HDL and apoA‐I in Glycemic Control, Insulin Sensitivity and β‐Cell Function
| Topic | Outcome | Reference |
|---|---|---|
| Association of HDL‐C and apoA‐I levels with glycemic control | ||
| Subjects with T2DM | Serum HDL‐C, apoA‐I, and HDL‐C/apoA‐I levels are inversely associated with insulin resistance by HOMA‐IR | 9 |
| Subjects with impaired glucose tolerance | ApoA‐I level is an independent risk factor for glucose tolerance | 10 |
| HDL and apoA‐I in glucose disposal/insulin sensitivity | ||
| Primary human skeletal muscle cells | ApoA‐I improves insulin‐dependent and ‐independent glucose uptake | 27 |
| C2C12 skeletal muscle cells | ApoA‐I increases glucose uptake by phosphorylation of AMPK | 35 |
| High‐fat–fed C57BL/6 mice | ApoA‐I improves insulin sensitivity by reducing systemic and hepatic inflammation | 40 |
| db/db mice | Long‐term HDL infusion improves glucose tolerance by activating GSK‐3 and AMPK in skeletal muscle | 37 |
| Pregnant female Wistar rats | ApoA‐I infusions increase insulin sensitivity, reduces systemic inflammation and protects against pregnancy‐induced insulin resistance | 45 |
| Subjects with T2DM | A single rHDL infusion reduces plasma glucose levels by increasing insulin secretion and promoting glucose uptake in skeletal muscle | 2 |
| HDL and apoA‐I in β‐cell function | ||
| Min6 insulinoma cells | HDLs isolated from normal human plasma, rHDLs, and apoA‐I increase Ins1 and Ins2 gene transcription and GSIS | 58 |
| Ins‐1E insulinoma cells | ApoA‐I increases Pdx1 gene transcription and GSIS | 57 |
| βTC3 insulinoma cells | Incubation with HDL protects βTC3 cells against LDL‐induced apoptosis | 70 |
| C57BL/6 mice | ApoA‐I infusions increase insulin secretion and improve glucose tolerance | 52 |
| High‐fat–fed C57BL/6 mice | Short‐term apoA‐I treatment increases GSIS and improves glucose clearance independent of insulin secretion | 53 |
| Mice with conditional deletion of ABCA1 and ABCG1 in β cells | ApoA‐I infusions increase GSIS in islets isolated from mice with elevated islet cholesterol levels | 54 |
| Healthy subjects and Min6 cells | CETP inhibition increases plasma HDL‐C, apoA‐I, and insulin levels in normal human subjects. Plasma from these subjects also increases GSIS in Min6 cells pretreated with oxidized LDLs | 60 |
| Isolated human islets | HDL protects human islets against oxidized LDL‐induced apoptosis | 71 |
| Isolated human and mouse islets | HDL protects human and mouse islets from interleukin‐1β– and glucose‐induced apoptosis | 72 |
AMPK indicates adenosine monophosphate‐activated protein kinase; apoA‐I, apolipoprotein A‐I; CETP, cholesteryl ester transfer protein; GSIS, glucose‐stimulated insulin secretion; GSK, glycogen synthase kinase‐3; HDL, high‐density lipoprotein; HDL‐C, high‐density lipoprotein cholesterol; HOMA‐IR, Homeostatic model assessment of insulin resistance; LDL, low‐density lipoprotein; rHDL, reconstituted HDL.