| First Author | Collier JJ | Year | 2020 |
| Journal | Mol Metab | Volume | 44 |
| Pages | 101140 | PubMed ID | 33285301 |
| Mgi Jnum | J:300481 | Mgi Id | MGI:6502880 |
| Doi | 10.1016/j.molmet.2020.101140 | Citation | Collier JJ, et al. (2020) Pancreatic, but not myeloid-cell, expression of interleukin-1alpha is required for maintenance of insulin secretion and whole body glucose homeostasis. Mol Metab 44:101140 |
| abstractText | OBJECTIVE: The expression of the interleukin-1 receptor type I (IL-1R) is enriched in pancreatic islet beta-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-1alpha as a highly inducible gene in response to IL-1R activation. In addition, IL-1alpha is elevated in mouse and rat models of obesity and Type 2 diabetes. Since less is known about the biology of IL-1alpha relative to IL-1beta in pancreatic tissue, our objective was to investigate the contribution of IL-1alpha to pancreatic beta-cell function and overall glucose homeostasis in vivo. METHODS: We generated a novel mouse line with conditional IL-1alpha alleles and subsequently produced mice with either pancreatic- or myeloid lineage-specific deletion of IL-1alpha. RESULTS: Using this in vivo approach, we discovered that pancreatic (IL-1alpha(Pdx1-/-)), but not myeloid-cell, expression of IL-1alpha (IL-1alpha(LysM-/-)) was required for the maintenance of whole body glucose homeostasis in both male and female mice. Moreover, pancreatic deletion of IL-1alpha 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-1alpha(Pdx1-/-) mice. Alternatively, IL-1alpha(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-1alpha to promote glucose homeostasis by supporting glucose-stimulated insulin secretion and islet beta-cell mass in vivo. |
