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The role of interleukin-1β in glucose metabolism during pregnancy and in gestational diabetes mellitus

Schulze, Friederike. The role of interleukin-1β in glucose metabolism during pregnancy and in gestational diabetes mellitus. 2017, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_12666

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Abstract

Pregnancy leads to adaptations of the maternal metabolism and immune system. Increased levels of steroid hormones induce insulin resistance, leading to a glucose gradient from the mother to the fetus, which is modulated by changes in insulin secretion. The maternal adaptive and innate immune systems are modified to accept the fetus, a semi-allograft.
Gestational diabetes mellitus occurs in genetically predisposed women and is associated with obesity and ageing. It is characterized by a further increase of insulin resistance and insufficient insulin secretion. The immune system of women with gestational diabetes is tilted toward inflammation, e.g. with higher interleukin-1β (IL-1β) expression in the adipose tissues and the placenta, and with higher levels of circulating IL-1β.
We investigated the role of IL-1β in glucose metabolism during pregnancy in young chow-fed mice, and older mice fed high-fat diet. To study the effect of IL-1β, a neutralizing anti-IL-1β antibody and IL-1β-deficient mice were used.
Pregnancy impaired glucose tolerance and increased circulating IL-1β and Il1b gene expression in the uterus of chow-fed mice and of high-fat diet-fed mice compared to their respective non-pregnant controls. Antagonizing IL-1β improved glucose tolerance of pregnant chow-fed mice and of older high-fat diet-fed mice. Similarly, pregnant IL-1β KO mice showed improved glucose tolerance compared to pregnant littermate control mice, supporting the hypothesis that IL-1β plays a role in pregnancy-induced glucose intolerance. Further, antagonizing IL-1β reduced serum levels of several steroid hormones in healthy pregnant mice.
We conclude, that IL-1β contributes to the impairment of glucose metabolism during pregnancy, possibly via modulation of steroid hormones.
Advisors:Palmer, Ed and Donath, Marc and Hess, Christoph
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Nephrologie > Exp. Transplantationsimmunologie und Nephrologie (Palmer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Nephrologie > Exp. Transplantationsimmunologie und Nephrologie (Palmer)
05 Faculty of Science
UniBasel Contributors:Palmer, Ed and Donath, Marc and Hess, Christoph
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:12666
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (65 Blätter)
Language:English
Identification Number:
Last Modified:06 Jul 2018 04:30
Deposited On:05 Jul 2018 09:01

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