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Review
. 2020 Jan 7;9(1):e013531.
doi: 10.1161/JAHA.119.013531. Epub 2019 Dec 31.

Role of High-Density Lipoproteins in Cholesterol Homeostasis and Glycemic Control

Bikash Manandhar  1 , Blake J Cochran  1 , Kerry-Anne Rye  1
Affiliations
Review

Role of High-Density Lipoproteins in Cholesterol Homeostasis and Glycemic Control

Bikash Manandhar et al. J Am Heart Assoc. .
No abstract available

Keywords: HDL; cholesterol; diabetes mellitus; glycemic control; insulin sensitivity; β‐cell function.

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Figures

Figure 1
Figure 1
HDL and apoA‐I improve insulin sensitivity and glucose uptake in skeletal muscle. ApoA‐I and HDLs activate GSK‐3 and AMPK. They also increase glucose uptake via increased insulin‐mediated activation of the PI3K/Akt pathway resulting in increased GLUT4 translocation to the cell surface. ABCA1 indicates ATP‐binding cassette transporter A1; AMPK, adenosine monophosphate‐activated protein kinase; apoA‐I, apolipoprotein A‐I; AS160, Akt substrate of 160 kDa; GLUT4, glucose transporter type 4; GSK‐3, glycogen synthase kinase‐3; HDL, high‐density lipoprotein; InsR, insulin receptor; IRS‐1, insulin receptor substrate‐1; PI3K, phosphoinositide‐3‐K; SR‐B1, scavenger receptor class B type 1.
Figure 2
Figure 2
Insulin synthesis and secretion is increased in apoA‐I treated pancreatic β cells via a PKA‐FoxO1 dependent mechanism. Interaction between apoA‐I and ABCA1 at the cell surface results in (A) activation of the Gαs subunit of the heterotrimeric G protein and (B) activation of adenylate cyclase which converts ATP to cAMP. Elevated cAMP levels activate PKA (C), which translocates to the nucleus, where it phosphorylates and excludes FoxO1 (D), resulting in derepression of insulin gene transcription (E). Activated PKA also increases intracellular calcium levels (F), and increases insulin secretion. ABCA1 indicates ATP‐binding cassette transporter A1; apoA‐I, apolipoprotein A‐I; FoxO1, forkhead box protein O1; PKA, protein kinase A.
Figure 3
Figure 3
Summary of mouse models used to study the impact of deletion of ABCA1 and/or ABCG1 on β‐cell function. ABCA1 indicates ATP‐binding cassette transporter A1; ABCG1 indicates ATP‐binding cassette transporter G1.
See this image and copyright information in PMC

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