Clinic for Endocrinology, Diabetes & Metabolism and Department Biomedicine, University Hospital Basel, Basel, Switzerland.
Nat Med. 2011 Oct 30;17(11):1481-9. doi: 10.1038/nm.2513.
Exercise, obesity and type 2 diabetes are associated with elevated plasma concentrations of interleukin-6 (IL-6). Glucagon-like peptide-1 (GLP-1) is a hormone that induces insulin secretion. Here we show that administration of IL-6 or elevated IL-6 concentrations in response to exercise stimulate GLP-1 secretion from intestinal L cells and pancreatic alpha cells, improving insulin secretion and glycemia. IL-6 increased GLP-1 production from alpha cells through increased proglucagon (which is encoded by GCG) and prohormone convertase 1/3 expression. In models of type 2 diabetes, the beneficial effects of IL-6 were maintained, and IL-6 neutralization resulted in further elevation of glycemia and reduced pancreatic GLP-1. Hence, IL-6 mediates crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand. This previously unidentified endocrine loop implicates IL-6 in the regulation of insulin secretion and suggests that drugs modulating this loop may be useful in type 2 diabetes.
运动、肥胖和 2 型糖尿病与白细胞介素-6（IL-6）的血浆浓度升高有关。胰高血糖素样肽-1（GLP-1）是一种能促进胰岛素分泌的激素。在这里，我们发现 IL-6 的给药或运动引起的 IL-6 浓度升高刺激肠 L 细胞和胰腺 alpha 细胞分泌 GLP-1，从而改善胰岛素分泌和血糖水平。IL-6 通过增加 proglucagon（由 GCG 编码）和前激素转化酶 1/3 的表达来增加 alpha 细胞中的 GLP-1 产生。在 2 型糖尿病模型中，IL-6 的有益作用得以维持，而 IL-6 中和则导致血糖进一步升高和胰腺 GLP-1 减少。因此，IL-6 介导对胰岛素敏感的组织、肠 L 细胞和胰岛之间的串扰，以适应胰岛素需求的变化。这个以前未被识别的内分泌环提示 IL-6 参与了胰岛素分泌的调节，并表明调节这个环的药物可能对 2 型糖尿病有用。
