High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus

Drew, Brian G., Duffy, Stephen J., Formosa, Melissa F., Natoli, Alaina K., Henstridge, Darren C., Penfold, Sally A., Thomas, Walter G., Mukhamedova, Nigora, de Courten, Barbora, Forbes, Josephine M., Yap, Felicia Y., Kaye, David M., van Hall, Gerrit, Febbraio, Mark A., Kemp, Bruce E., Sviridov, Dmitri, Steinberg, Gregory R. and Kingwell, Bronwyn A. (2009) High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus. Circulation, 119 15: 2103-2111. doi:10.1161/CIRCULATIONAHA.108.843219


Author Drew, Brian G.
Duffy, Stephen J.
Formosa, Melissa F.
Natoli, Alaina K.
Henstridge, Darren C.
Penfold, Sally A.
Thomas, Walter G.
Mukhamedova, Nigora
de Courten, Barbora
Forbes, Josephine M.
Yap, Felicia Y.
Kaye, David M.
van Hall, Gerrit
Febbraio, Mark A.
Kemp, Bruce E.
Sviridov, Dmitri
Steinberg, Gregory R.
Kingwell, Bronwyn A.
Title High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus
Journal name Circulation   Check publisher's open access policy
ISSN 0009-7322
1524-4539
Publication date 2009-04-21
Year available 2009
Sub-type Article (original research)
DOI 10.1161/CIRCULATIONAHA.108.843219
Open Access Status Not Open Access
Volume 119
Issue 15
Start page 2103
End page 2111
Total pages 9
Place of publication Philadelphia, PA United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract
Background— Low plasma high-density lipoprotein (HDL) is associated with elevated cardiovascular risk and aspects of the metabolic syndrome. We hypothesized that HDL modulates glucose metabolism via elevation of plasma insulin and through activation of the key metabolic regulatory enzyme, AMP-activated protein kinase, in skeletal muscle.

Methods and Results— Thirteen patients with type 2 diabetes mellitus received both intravenous reconstituted HDL (rHDL: 80 mg/kg over 4 hours) and placebo on separate days in a double-blind, placebo-controlled crossover study. A greater fall in plasma glucose from baseline occurred during rHDL than during placebo (at 4 hours rHDL=−2.6±0.4; placebo=−2.1±0.3mmol/L; P=0.018). rHDL increased plasma insulin (at 4 hours rHDL=3.4±10.0; placebo= −19.2±7.4 pmol/L; P=0.034) and also the homeostasis model assessment β-cell function index (at 4 hours rHDL=18.9±5.9; placebo=8.6±4.4%; P=0.025). Acetyl-CoA carboxylase β phosphorylation in skeletal muscle biopsies was increased by 1.7±0.3-fold after rHDL, indicating activation of the AMP-activated protein kinase pathway. Both HDL and apolipoprotein AI increased glucose uptake (by 177±12% and 144±18%, respectively; P<0.05 for both) in primary human skeletal muscle cell cultures established from patients with type 2 diabetes mellitus (n=5). The mechanism is demonstrated to include stimulation of the ATP-binding cassette transporter A1 with subsequent activation of the calcium/calmodulin-dependent protein kinase kinase and the AMP-activated protein kinase pathway.

Conclusions— rHDL reduced plasma glucose in patients with type 2 diabetes mellitus by increasing plasma insulin and activating AMP-activated protein kinase in skeletal muscle. These findings suggest a role for HDL-raising therapies beyond atherosclerosis to address type 2 diabetes mellitus.
Keyword Glucose
Insulin
Lipoproteins
Metabolism
Muscles
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Mater Research Institute-UQ (MRI-UQ)
 
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