ApoA-1 improves glucose tolerance by increasing glucose uptake into heart and skeletal muscle independently of AMPKα2

Acute administration of the main protein component of high-density lipoprotein, apolipoprotein A-I (ApoA-1), improves glucose uptake in skeletal muscle. The molecular mechanisms mediating this are not known, but in muscle cell cultures, ApoA-1 failed to increase glucose uptake when infected with a d...

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Bibliographic Details
Published in:Molecular metabolism (Germany) 2020-05, Vol.35, p.100949, Article 100949
Main Authors: Fritzen, Andreas Mæchel, Domingo-Espín, Joan, Lundsgaard, Anne-Marie, Kleinert, Maximilian, Israelsen, Ida, Carl, Christian S., Nicolaisen, Trine S., Kjøbsted, Rasmus, Jeppesen, Jacob F., Wojtaszewski, Jørgen F.P., Lagerstedt, Jens O., Kiens, Bente
Format: Article
Language:English
Subjects:
AMP-Activated protein kinase (AMPK)
Apolipoprotein A-1 (ApoA-1)
Basic Medicine
Clinical Medicine
Endocrinology and Diabetes
Endokrinologi och diabetes
Fysiologi
Glucose uptake
Insulin
Klinisk medicin
Medical and Health Sciences
Medicin och hälsovetenskap
Medicinska och farmaceutiska grundvetenskaper
Metabolism
Original
Physiology
Skeletal muscle
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Summary:Acute administration of the main protein component of high-density lipoprotein, apolipoprotein A-I (ApoA-1), improves glucose uptake in skeletal muscle. The molecular mechanisms mediating this are not known, but in muscle cell cultures, ApoA-1 failed to increase glucose uptake when infected with a dominant-negative AMP-activated protein kinase (AMPK) virus. We therefore investigated whether AMPK is necessary for ApoA-1-stimulated glucose uptake in intact heart and skeletal muscle in vivo. The effect of injection with recombinant human ApoA-1 (rApoA-1) on glucose tolerance, glucose-stimulated insulin secretion, and glucose uptake into skeletal and heart muscle with and without block of insulin secretion by injection of epinephrine (0.1 mg/kg) and propranolol (5 mg/kg), were investigated in 8 weeks high-fat diet-fed (60E%) wild-type and AMPKα2 kinase-dead mice in the overnight-fasted state. In addition, the effect of rApoA-1 on glucose uptake in isolated skeletal muscle ex vivo was studied. rApoA-1 lowered plasma glucose concentration by 1.7 mmol/l within 3 h (6.1 vs 4.4 mmol/l; p 
ISSN:2212-8778
2212-8778
DOI:10.1016/j.molmet.2020.01.013