Jelleschitz Julia, Heider Sophie, Kehm Richard, Baumgarten Patricia, Ott Christiane, Schnell Vanessa, Grune Tilman, Höhn Annika
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Redox Biol. 2025 May;82:103587. doi: 10.1016/j.redox.2025.103587. Epub 2025 Mar 6.
With increasing age, the risk for age-related type-2-diabetes also increases due to impaired glucose tolerance and insulin secretion. This disease process may be influenced by various factors, including immune cell triggered inflammation and fibrosis. Although immune cells are a necessary component of islets, little is known about immune cell accumulation, immune cell subtype shifts and subsequent influence on glucose metabolism in healthy aging. However, this is critical for understanding the mechanisms that influence β-cell health. Therefore, we studied young and old male C57BL/6J mice, focusing on immune cell composition, patterns of accumulation, and the presence of fibrosis within the pancreatic islets. Our findings demonstrate that insulitis occurs in healthy aged mice without immediate development of a diabetic phenotype. Aged islets exhibited an increase in leukocytes and a shift in immune cell composition. While insulitis typically involves excessive immune cell accumulation, we observed a moderate increase in macrophages and T-cells during aging, which may support β-cell proliferation via cytokine secretion. In fact, aged mice in our study showed an increase in β-cell mass as well as a partially higher insulin secretory capacity, which compensated for the loss of β-cell functionality in insulitic islets and led to improved glucose tolerance. Furthermore, fibrosis which is normally triggered by immune cells, increased with age but appears to reach a steady state, emphasizing the importance of counter-regulatory mechanisms and immune system regulation. Our results suggest, that immune cell subtypes change with age and that non-pathological accumulation of immune-cells may regulate glucose metabolism through secretion of cytokines.
随着年龄的增长，由于葡萄糖耐量受损和胰岛素分泌受损，与年龄相关的2型糖尿病风险也会增加。这个疾病过程可能受到多种因素的影响，包括免疫细胞引发的炎症和纤维化。尽管免疫细胞是胰岛的必要组成部分，但对于健康衰老过程中免疫细胞的积累、免疫细胞亚型的转变以及对葡萄糖代谢的后续影响，我们知之甚少。然而，这对于理解影响β细胞健康的机制至关重要。因此，我们研究了年轻和年老的雄性C57BL/6J小鼠，重点关注免疫细胞组成、积累模式以及胰岛内纤维化的存在情况。我们的研究结果表明，健康的老年小鼠会发生胰岛炎，但不会立即出现糖尿病表型。老年胰岛中白细胞数量增加，免疫细胞组成发生转变。虽然胰岛炎通常涉及免疫细胞的过度积累，但我们观察到衰老过程中巨噬细胞和T细胞适度增加，这可能通过细胞因子分泌来支持β细胞增殖。事实上，我们研究中的老年小鼠β细胞数量增加，胰岛素分泌能力也部分提高，这补偿了胰岛炎胰岛中β细胞功能的丧失，从而改善了葡萄糖耐量。此外，通常由免疫细胞引发的纤维化随年龄增长而增加，但似乎达到了稳定状态，这强调了反调节机制和免疫系统调节的重要性。我们的结果表明，免疫细胞亚型会随年龄变化，免疫细胞的非病理性积累可能通过细胞因子分泌来调节葡萄糖代谢。
