(DCP008) EFFECTS OF ACTOVEGIN ON LIVER AND CARDIAC MITOCHONDRIAL RESPIRATION IN TYPE 1 DIABETES

Background: Insulin deficiency in type 1 diabetes leads to an impairment of glucose metabolism and mitochondrial function in cardiomyocytes and hepatocytes. Actovegin is a hemodialysate of calf blood which has been shown to enhance glucose uptake and cell metabolism in healthy human skeletal muscle. The objectives of this study were to determine the effect of Actovegin on cardiac and liver mitochondrial respiration in a type 1 diabetic mouse model. Outcomes on blood glucose, body mass, and water consumption were also investigated.

METHODS AND RESULTS: Type 1 diabetic, male, C57Bl/6 mice were randomized to an Actovegin and a control group. Every third day, for 14 days, the Actovegin (n = 10) and control group (n = 9) were injected intraperitoneally with 0.1 ml (25% v/v) Actovegin and 0.1 ml physiological salt solution, respectively. Mitochondrial respiratory capacity of the heart and liver was measured by high resolution respirometry (Oroboros Oxygraph). Blood glucose was assessed using a glucometer at Day 1, 7, and 14. Body mass and water consumption were evaluated every second day using an electronic balance scale. An independent samples T-test was used to establish between-group differences for cardiac mitochondrial respiration, body mass and water consumption. A Mann-Whitney-U test was used to compare the mean difference between groups for liver mitochondrial respiration and blood glucose concentration.

Results: After 14 days, compared to the control group, the Actovegin group demonstrated a significantly higher maximal liver mitochondrial respiration (Actovegin: 120 pmol/sec*mg versus control: 100 pmol/sec*mg, P = 0.028). There were no significant differences between groups for maximal cardiac mitochondrial respiration (Actovegin: 327 pmol/sec*mg versus control: 256 pmol/sec*mg, P = 0.187). At Day 14, the Actovegin group trended towards a lower blood glucose concentration than the control group (Actovegin: 31.4 mmol/L versus control 33.3 mmol/L, P = 0.083). There were no significant differences between groups for body mass or water consumption (P > 0.600).

Conclusion: Actovegin injections over two weeks can significantly improve oxidative phosphorylation capacity of liver mitochondria in type 1 diabetes. Despite the severe hyperglycemic state of the type 1 diabetic mice, a trend pointed towards reduced blood glucose levels in those treated with Actovegin. Further investigation into the mechanistic action of Actovegin is warranted to establish an understanding of how liver mitochondria and glucose uptake benefit from this drug.