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Hyperinsulinemia due to altered insulin secretion contributes to insulin resistance in chronic intermittent hypoxia independently of obesity

Joana F. Sacramento, Bernardete F. Melo, Elena Olea, Ana Obeso, Asuncion Rocher, Tiago Rodrigues, Jesus Prieto-Lloret, Sara Yubero, Emilia C. Monteiro, Paulo Matafome, Silva V. Conde
European Respiratory Journal 2019 54: OA4935; DOI: 10.1183/13993003.congress-2019.OA4935
Joana F. Sacramento
1CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
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  • For correspondence: joana.sacramento@nms.unl.pt
Bernardete F. Melo
1CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
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Elena Olea
2Department of Nursing, University of Valladolid, School of Nursing, Valladolid, Spain and Institute of Molecular Biology and Genetics, CIBER Enfermedades Respiratorias, CIBERES, Institute of Salud Carlos III, Valladolid, Spain
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Ana Obeso
3Department of Biochemistry and Molecular Biology and Physiology, University of Valladolid, School of Medicine and Institute of Molecular Biology and Genetics, CIBER Enfermedades Respiratorias, CIBERES, Institute of Salud Carlos III, Valladolid, Spain
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Asuncion Rocher
3Department of Biochemistry and Molecular Biology and Physiology, University of Valladolid, School of Medicine and Institute of Molecular Biology and Genetics, CIBER Enfermedades Respiratorias, CIBERES, Institute of Salud Carlos III, Valladolid, Spain
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Tiago Rodrigues
4Institute of Physiology and Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
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Jesus Prieto-Lloret
3Department of Biochemistry and Molecular Biology and Physiology, University of Valladolid, School of Medicine and Institute of Molecular Biology and Genetics, CIBER Enfermedades Respiratorias, CIBERES, Institute of Salud Carlos III, Valladolid, Spain
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Sara Yubero
3Department of Biochemistry and Molecular Biology and Physiology, University of Valladolid, School of Medicine and Institute of Molecular Biology and Genetics, CIBER Enfermedades Respiratorias, CIBERES, Institute of Salud Carlos III, Valladolid, Spain
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Emilia C. Monteiro
1CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
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Paulo Matafome
5Institute of Physiology and Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra and Instituto Politécnico de Coimbra, Coimbra Health School, Coimbra, Portugal
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Silva V. Conde
1CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
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Abstract

Clinical studies have demonstrated a link between obstructive sleep apnea (OSA) and insulin resistance (IR), however it is not clear which is the main event that determines IR development. We hypothesize that hyperinsulinemia is a main driver of IR in chronic intermittent hypoxia (CIH), that mimics OSA, independently of obesity, adipose tissue hypoxia and severity of CIH.

Male Wistar Rats were submitted to 2 CIH protocols: 1) a mild CIH paradigm obtained by 5/6 hypoxic (5%O2) cycles/h, 10.5 h/day during 35 days; and 2) a severe CIH paradigm obtained by 40 s, 5%O2/80 s, air, equivalent to an apnoea–hypopnoea index of 30, 8h/day for 14 days. CIH animals were compared with controls. Fasting glycemia, insulinemia, C-peptide and insulin sensitivity through KITTand HOMA index were measured. Insulin clearance was calculated. Weight and fat mass were assessed. Adipose tissue dysfunction and inflammation were assessed by evaluation of several proteins involved in insulin signaling pathways and hypoxia and inflammation pathways.

Mild CIH increased insulin secretion by 214% (CTLmildCIH =1.01±0.21ug/L) while severe CIH increased by 103% (CTLsevereCIH= 1.1±0.04ug/L) with no alterations in fasting glycemia in both CIH protocols. HOMA index increased by 112% in mild CIH and by 108% in severe CIH animals. None of CIH protocols alter weight gain and fat mass deposition. Mild and severe CIH increased IR in adipose tissue, with no changes in HIF1 and 2α expression.

We can conclude that both mild and severe CIH protocols induce insulin resistance, which is associated with an increase insulin secretion by the pancreas being independent of obesity and fat mass.

  • Hypoxia
  • Animal models

Footnotes

Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, OA4935.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2019
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Hyperinsulinemia due to altered insulin secretion contributes to insulin resistance in chronic intermittent hypoxia independently of obesity
Joana F. Sacramento, Bernardete F. Melo, Elena Olea, Ana Obeso, Asuncion Rocher, Tiago Rodrigues, Jesus Prieto-Lloret, Sara Yubero, Emilia C. Monteiro, Paulo Matafome, Silva V. Conde
European Respiratory Journal Sep 2019, 54 (suppl 63) OA4935; DOI: 10.1183/13993003.congress-2019.OA4935

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Hyperinsulinemia due to altered insulin secretion contributes to insulin resistance in chronic intermittent hypoxia independently of obesity
Joana F. Sacramento, Bernardete F. Melo, Elena Olea, Ana Obeso, Asuncion Rocher, Tiago Rodrigues, Jesus Prieto-Lloret, Sara Yubero, Emilia C. Monteiro, Paulo Matafome, Silva V. Conde
European Respiratory Journal Sep 2019, 54 (suppl 63) OA4935; DOI: 10.1183/13993003.congress-2019.OA4935
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