Endocrine Abstracts

Background: Insulin is well-known as an anabolic hormone and growth factor that mediates glucose and lipid metabolism. Insulin signaling dysregulation causes a cascade of adverse effects, leading to development of cardiometabolic diseases such as type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease. Men and women are noted to have different disease progression and outcomes with T2DM women having increased relative risk for fatal and non-fatal cardiovascular disease compared to men. These differences have been suggested to stem from sex differences in insulin resistance. With insulin resistance and inflammation being a common phenome underlying cardiometabolic disease pathophysiology, it has been increasingly recognized insulin plays a major role in macrophage mediated-inflammation. Published studies are contradictory in opinions if insulin primes macrophages to be proinflammatory or anti-inflammatory with limited studies investigating female macrophages. We aim to investigate if male and female macrophages respond differently to insulin.

Methods: Bone-marrow derived macrophages (BMDM) from wild-type C57BL/6J male and female mice (n = 4-6) were harvested and stimulated with 0.1-100 nM of insulin for 2- or 24-hours. RT-qPCR was used to analyze changes in mRNA expression. Results were analyzed using a two-way ANOVA using fisher’s least significant difference test.

Results: 2-hour stimulation showed insulin increased female Ccl2, Tnf-a and Il-10 and decreased Il-1b mRNA expression compared to males. 24-hours stimulation showed insulin increased female Akt2, Nf-kB, Ccl2, Il- 1b, Il-10 and Tnf-a and decreased Tlr4 mRNA expression.

Conclusion: Our results demonstrate male and female BMDMs respond differently to insulin. Female BMDMs showed increased pro-inflammatory gene expression when stimulated for 24-hours. Female BMDMs also displayed increased Il-10 gene expression at 2- and 24-hours. This points to female macrophages response being more sensitive to insulin signaling. These results could be used to inform current therapeutic strategies and with the view to improve cardiometabolic disease outcome in females.