Diabetologie und Stoffwechsel 2014; 9 - FV34
DOI: 10.1055/s-0034-1374891

Long-term effects of chronic variable stress on insulin sensitivity

S Müller-Lühlhoff 1, T Jelenik 2, S Hartwig 1, S Lehr 1, P Nowotny 2, M Roden 2, 3, H Al-Hasani 1, TR Castañeda 1
  • 1German Diabetes Center, Heinrich Heine University, Leibniz Center for Diabetes Research, Institute for Clinical Biochemistry and Pathobiochemistry, Düsseldorf, Germany
  • 2German Diabetes Center, Heinrich Heine University, Leibniz Center for Diabetes Research, Institute for Clinical Diabetology, Düsseldorf, Germany
  • 3University Clinics Düsseldorf, Heinrich Heine University, Departments of Endocrinology and Diabetology and Metabolic Diseases, Düsseldorf, Germany

Aim: Stress is a state of threat to homeostasis and increases the incidence of type-2 diabetes. However, the long-term effects of chronic stress on insulin sensitivity are yet unknown. We aimed to characterize how chronic variable stress (CVS) affects insulin sensitivity on the long-term in mice.

Methods: Age- and body weight (BW)-matched male C57BL/6 mice were exposed to a random series of stressors for 15 days (CVS, n = 12), controls were housed separately (Ctrl, n = 12). Body composition was analyzed by NMR. Plasma corticosterone was analyzed with RIA. Three months after CVS insulin sensitivity was analyzed in vivo by hyperinsulinemic-euglycemic clamp. Plasma hormones and cytokines were analyzed with multiplex immunoassay. Statistical differences were considered significant at p < 0.05 (two-tailed unpaired t-test).

Results: CVS mice had lower BW (25.48 ± 0.45 g, p < 0.001) and lean mass (23.08 ± 0.45 g, p < 0.01) compared to Ctrl (28.56 ± 0.49 g, 25.64 ± 0.56 g, respectively). Corticosterone was increased by 218% in CVS (p < 0.01). Three months later, the CVS group showed a trend to lower endogenous glucose production (EGP) (20.01 ± 1.12 vs. 23.86 ± 1.48 mg/kg/min, p = 0.055). Whole-body insulin sensitivity was higher in CVS (glucose infusion rate: 72.05 ± 3.72 vs. 62.16 ± 2.18 mg/kg/min, p < 0.05). Glucose turnover in peripheral tissues was increased (363.30 ± 28.71 vs. 275 ± 16.71%, p < 0.05), while suppression of EGP by insulin was unaffected (101.80 ± 6.14 vs. 91.54 ± 8.84%, p > 0.05). Finally, CVS mice had lower adiponectin (5875 ± 430.3 vs. 11290 ± 1389 ng/ml, p < 0.01) compared to Ctrl.

Conclusions: CVS long-term consequences include increased insulin sensitivity and elevated glucose turnover in peripheral tissues.

Acknowledgements: DDZ, TFG 2012