Inflammatory Cytokines and Biomarkers in Aging Type 2 Diabetic Rats

Aging, type 2 diabetes mellitus (T2DM), and cardiovascular disease are all associated with systematic low grade inflammation. Accordingly, these conditions alter circulating concentrations of cytokines involved in inflammation and vascular function. Recent studies suggest that these same cytokines may contribute to the sensitization of group III and IV afferents, which are involved in evoking the exercise pressor reflex during skeletal muscle contraction. The purpose of this study was to determine the concentrations of cytokines involved in inflammation and vascular function in aging T2DM rats. To accomplish this we analyzed blood samples drawn from UC Davis T2DM rats at 4 months (BW: 549 ±29 g, glucose: 337±147 mg/dl, HbA1c: 7.4±0.6%, insulin: 5129±3799 pg/ml), 8 months (BW: 546±77 g, glucose: 549±46 mg/dl, insulin: 288±416 pg/ml), and 12 months (BW: 512±144 g, glucose: 551±57 mg/dl, HbA1c: 11.9±2.4%, insulin: 436±167 pg/ml) of age. We used healthy, adult (CTL) Sprague Dawley rats (BW: 465±18 g, glucose: 200±14 mg/dl, HbA1c: 4.7±0.1%, insulin: 1692±1422 pg/ml) as controls. We analyzed serum samples, to determine the concentration of circulating IL‐1β, IL‐10, IL‐4, and insulin, using rat cytokine/chemokine and adipokine multiplex kits (EMD Millipore)and a Bio‐Plex 200 instrument. We found that the concentration of the pro‐inflammatory cytokine IL‐1β gradually, although not significantly, increased in T2DM rats as they aged compared to CTL rats (4 mo: 49±18 pg/ml, n=4; 8 mo: 72±48 pg/ml, n=9; 12 mo: 71±24 pg/ml, n=6; CTL: 38±12 pg/ml, n=6). The concentration of the anti‐inflammatory cytokine IL‐10 decreased in T2DM rats as they aged compared to CTL (4 mo: 542±454 pg/ml, n=4; 8 mo: 112±168 pg/ml, n=8; 12 mo: 467±264 pg/ml, n=6; CTL: 1289±527 pg/ml, n=4; p<0.05). The concentration of the anti‐inflammatory cytokine IL‐4 appears to be more variable over time in T2DM rats as it decreased at 4 mo and 8 mo of age and then increased at 12 mo of age (4 mo: 18±15 pg/ml, n=4; 8 mo: 8±12 pg/ml, n=8; 12 mo: 49±7 pg/ml, n=5; CTL: 25±21 pg/ml, n=6; p<0.05). These results suggest that circulating concentrations of pro‐inflammatory and anti‐inflammatory cytokines are altered in aging T2DM rats and they may be increased or decreased depending on duration of the disease. Additionally, these changes in inflammatory cytokines may play a role in exaggerating the exercise pressor reflex in aging T2DM rats. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .