Dataset Information
Pancreatic, but not myeloid-cell, expression of interleukin-1alpha is required for maintenance of insulin secretion and whole body glucose homeostasis.
Ontology highlight
ABSTRACT: Objective
The expression of the interleukin-1 receptor type I (IL-1R) is enriched in pancreatic islet ?-cells, signifying that ligands activating this pathway are important for the health and function of the insulin-secreting cell. Using isolated mouse, rat, and human islets, we identified the cytokine IL-1? as a highly inducible gene in response to IL-1R activation. In addition, IL-1? is elevated in mouse and rat models of obesity and Type 2 diabetes. Since less is known about the biology of IL-1? relative to IL-1? in pancreatic tissue, our objective was to investigate the contribution of IL-1? to pancreatic ?-cell function and overall glucose homeostasis in vivo.Methods
We generated a novel mouse line with conditional IL-1? alleles and subsequently produced mice with either pancreatic- or myeloid lineage-specific deletion of IL-1?.Results
Using this in vivo approach, we discovered that pancreatic (IL-1?Pdx1-/-), but not myeloid-cell, expression of IL-1? (IL-1?LysM-/-) was required for the maintenance of whole body glucose homeostasis in both male and female mice. Moreover, pancreatic deletion of IL-1? led to impaired glucose tolerance with no change in insulin sensitivity. This observation was consistent with our finding that glucose-stimulated insulin secretion was reduced in islets isolated from IL-1?Pdx1-/- mice. Alternatively, IL-1?LysM-/- mice (male and female) did not have any detectable changes in glucose tolerance, respiratory quotient, physical activity, or food intake when compared with littermate controls.Conclusions
Taken together, we conclude that there is an important physiological role for pancreatic IL-1? to promote glucose homeostasis by supporting glucose-stimulated insulin secretion and islet ?-cell mass in vivo.
SUBMITTER: Collier JJ
PROVIDER: S-EPMC7772372 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Publications
Pancreatic, but not myeloid-cell, expression of interleukin-1alpha is required for maintenance of insulin secretion and whole body glucose homeostasis.
Molecular metabolism 20201205
<h4>Objective</h4>The expression of the interleukin-1 receptor type I (IL-1R) is enriched in pancreatic islet β-cells, signifying that ligands activating this pathway are important for the health and function of the insulin-secreting cell. Using isolated mouse, rat, and human islets, we identified the cytokine IL-1α as a highly inducible gene in response to IL-1R activation. In addition, IL-1α is elevated in mouse and rat models of obesity and Type 2 diabetes. Since less is known about the biolo ...[more]
