Endocrine Abstracts

More than two billion people worldwide are overweight or obese. Excess caloric intake triggers local and systemic inflammatory responses¹. Specifically, in the gut, obesity induces increased permeability and remodelling of the intestinal tissues². The small intestine has a crucial role in the regulation of glucose homeostasis, through its role in the sensing, digestion and absorption of nutrients, and the secretion of insulin-stimulating peptide hormones³. However, the mechanisms connecting glucose homeostasis and small intestinal integrity are poorly characterised. To investigate how changes in small intestinal inflammation and permeability influence glucose tolerance, lean C57Black6/J mice were treated with an RNA analogue (Poly I:C) to induce intestinal inflammation and damage, or saline control. In addition, we used Tally Ho mice, a model of obesity and type 2 diabetes. All mice were fed a chow diet and monitored for intestinal permeability using FITC-dextran assay and glucose homeostasis using intraperitoneal glucose tolerance tests (IPGTT). Poly I:C induced intestinal damage as confirmed by histology. Poly I:C treatment in lean mice also induced an increase in intestinal permeability compared to saline-treated mice. Furthermore, Poly I:C induced glucose intolerance in a dose-dependent manner. Diabetic Tally Ho male mice had increased permeability compared to the obese but euglycemic littermate controls. Altogether, our preliminary data suggest that intestinal integrity plays a role in regulating glucose homeostasis.

References: 1. Lingvay I, et al. The Lancet. 2024;404(10456):972-87. 2. Winer D.A. et al. Metabolism. 2016;23(3):413-26. 3. Hickey JW, et al. Nature. 2023;619(7970):572-84.