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IL-1beta in the integration of nutrient-derived sensory information in health and obesity

Wiedemann, Sophia J. IL-1beta in the integration of nutrient-derived sensory information in health and obesity. 2021, Doctoral Thesis, University of Basel, Faculty of Science.

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Abstract

Our understanding of the mechanisms underlying the proper regulation of blood glucose levels remains incomplete. While IL-1β has been established as an important guardian of glucose homeostasis in mice, the precise mechanism of its stimulatory effect on insulin release continues to be a mystery. Here, we aim to further explore this insulin-secretagogue effect of IL-1β in both mice and humans. We especially aim to delineate IL-1β’s effects on specifically the cephalic phase of insulin release, which describes the initial vagally-mediated spike in insulin levels in response to the sight, smell and taste of food, as well as the proprioceptive and tactile stimulation by food.
Establishing a mouse model of cephalic phase insulin release, we found that it was mediated by IL-1β originating from long-lived CX3CR1+ myeloid cells. Furthermore, IL-1β regulated the activity of neurons of the paraventricular nucleus of the hypothalamus in response to cephalic stimulation and activated the vagus nerve to induce insulin secretion. Notably, cephalic phase insulin release was impaired in obesity, in both mice and humans, and in mice this was due to dysregulated IL-1β signaling. Next, confirming prior reports in rodents, we found that IL-1β also stimulated insulin secretion in human subjects. Furthermore, it significantly contributed to the pathophysiology of postprandial hypoglycemia, a disabling complication of bariatric surgery. In summary, we describe a regulatory role for IL-1β in the integration of nutrient-derived sensory information and subsequent neuronally-mediated insulin secretion.
Advisors:Donath, Marc Y. and Hess, Christoph and Lutz, Thomas A.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie > Endokrinologie, Diabetologie und Metabolismus (Donath)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie > Endokrinologie, Diabetologie und Metabolismus (Donath)
UniBasel Contributors:Hess, Christoph
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:14106
Thesis status:Complete
Number of Pages:102
Language:English
Identification Number:
  • urn: urn:nbn:ch:bel-bau-diss141068
edoc DOI:
Last Modified:25 Jun 2021 04:30
Deposited On:24 Jun 2021 09:29

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