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ApoA-1 improves glu...
ApoA-1 improves glucose tolerance by increasing glucose uptake into heart and skeletal muscle independently of AMPKα2
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- Fritzen, Andreas Mæchel (författare)
- University of Copenhagen
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- Domingo-Espín, Joan (författare)
- Lund University,Lunds universitet,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,Medical Protein Science,Lund University Research Groups
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- Lundsgaard, Anne Marie (författare)
- University of Copenhagen
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- Kleinert, Maximilian (författare)
- Helmholtz Zentrum München,University of Copenhagen
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- Israelsen, Ida (författare)
- University of Copenhagen
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- Carl, Christian S. (författare)
- University of Copenhagen
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- Nicolaisen, Trine S. (författare)
- University of Copenhagen
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- Kjøbsted, Rasmus (författare)
- University of Copenhagen
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- Jeppesen, Jacob F. (författare)
- Novo Nordisk, Inc., US
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- Wojtaszewski, Jørgen F.P. (författare)
- University of Copenhagen
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- Lagerstedt, Jens O. (författare)
- Lund University,Lunds universitet,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,LINXS - Institute of advanced Neutron and X-ray Science,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Medical Protein Science,Lund University Research Groups,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Kiens, Bente (författare)
- University of Copenhagen
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(creator_code:org_t)
- Elsevier BV, 2020
- 2020
- Engelska.
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Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 35
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Objective: 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. Methods: 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. Results: rApoA-1 lowered plasma glucose concentration by 1.7 mmol/l within 3 h (6.1 vs 4.4 mmol/l; p < 0.001). Three hours after rApoA-1 injection, glucose tolerance during a 40-min glucose tolerance test (GTT) was improved compared to control (area under the curve (AUC) reduced by 45%, p < 0.001). This was accompanied by an increased glucose clearance into skeletal (+110%; p < 0.001) and heart muscle (+100%; p < 0.001) and an increase in glucose-stimulated insulin secretion 20 min after glucose injection (+180%; p < 0.001). When insulin secretion was blocked during a GTT, rApoA-1 still enhanced glucose tolerance (AUC lowered by 20% compared to control; p < 0.001) and increased glucose clearance into skeletal (+50%; p < 0.05) and heart muscle (+270%; p < 0.001). These improvements occurred to a similar extent in both wild-type and AMPKα2 kinase-dead mice and thus independently of AMPKα2 activity in skeletal- and heart muscle. Interestingly, rApoA-1 failed to increase glucose uptake in isolated skeletal muscles ex vivo. Conclusions: In conclusion, ApoA-1 stimulates in vivo glucose disposal into skeletal and heart muscle independently of AMPKα2. The observation that ApoA-1 fails to increase glucose uptake in isolated muscle ex vivo suggests that additional systemic effects are required.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- AMP-Activated protein kinase (AMPK)
- Apolipoprotein A-1 (ApoA-1)
- Glucose uptake
- Insulin
- Metabolism
- Skeletal muscle
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- ref (ämneskategori)
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Fritzen, Andreas ...
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Domingo-Espín, J ...
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Lundsgaard, Anne ...
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Kleinert, Maximi ...
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Israelsen, Ida
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Carl, Christian ...
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Nicolaisen, Trin ...
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Kjøbsted, Rasmus
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Jeppesen, Jacob ...
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Wojtaszewski, Jø ...
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Lagerstedt, Jens ...
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Kiens, Bente
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