A. Kurabayashi, W. Iwashita, C. Tanaka, S. Naganuma, M. Furihata, K. Inoue, et al. (2020). Murine remote ischemic preconditioning suppresses diabetic ketoacidosis by enhancing glycolysis and entry into tricarboxylic acid cycle in the liver. Life sciences, 253, 117748. https://doi.org/10.1016/j.lfs.2020.117748

PubMed 32387415

[Abstract]
AIMS: Hindlimb ischemia-reperfusion (IR) was previously demonstrated by our group to decrease blood sugar levels by suppressing hepatic gluconeogenesis and enhancing glucose uptake using activation of the parasympathetic nervous system. While IR attenuated hyperglycemia in diabetic mice, it was unclear whether IR regulated energy metabolism in the liver. We investigated the mechanisms by which IR regulates energy metabolism in the liver from type1 diabetic mice.

MAIN METHODS: Streptozotocin-induced diabetic male C57BL/6J mice were used to determine the effect of IR on the factors involved in energy metabolism in the liver (i.e., activation levels of AMP-activated protein kinase, aconitase and pyruvate dehydrogenase; adenosine triphosphate and fumarate concentrations; sirtuin (Sirt) 1 expression). These various signaling pathways and key enzyme activities were examined using western blot analysis and a biochemical technique including a colorimetric assay.

KEY FINDINGS: Under feeding conditions (free access to normal murine chow and water), blood glucose levels and serum ketone body levels were significantly suppressed by IR, whereas phospho-AMP-activated protein kinase and its activity, pyruvate dehydrogenase, aconitase activity, and Sirt 1expression were upregulated. In contrast, peroxisome proliferator-activated receptor γ coactivator-1, which accelerated fatty acid use, was suppressed by IR.

SIGNIFICANCE: These results indicated that in the IR-treated diabetic liver, energy production was promoted through acceleration of the tricarboxylic acid cycle linked with increased glucose preference rather than fatty acid under feeding conditions. Therefore, IR may be beneficial against diabetic hyperglycemia, but also ketoacidosis.