Cinnamic Acid Improves Glucose Uptake and Utilization with Concomitant Improvement of Redox and Bioenergetic Homeostasis, While Modulating Glucose-Lipid Metabolic Switch in Isolated Psoas Muscle

The antidiabetic properties of cinnamic acid was investigated in isolated psoas muscles from Sprague Dawley male rats, by studying its ability to enhance glucose uptake and its modulatory effect on redox imbalance, purinergic activities, glucose, and lipid metabolism. The isolated muscles were incubated in cinnamic acid in the presence of glucose for 2 h at 37 °C. Negative control consisted of muscles incubated in “glucose only,” while the positive control consisted of muscles not incubated in cinnamic acid or glucose. The standard antidiabetic drug was metformin. Glucose uptake was enhanced in muscles incubated with cinnamic acid, with concomitant elevated levels of glutathione, superoxide dismutase, catalase, ENTPDase, and 5′nuclotidase activities. Cinnamic acid also caused depleted muscular levels of malondialdehyde, nitric oxide, ATPase, acetylcholinesterase, chymotrypsin, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glycogen phosphorylase, and lipase activities. Following incubation with glucose only, there were alterations in muscular lipid metabolites with concomitant activation of plasmalogen synthesis and mitochondrial β-oxidation of long chain saturated fatty acids pathways. Incubation with cinnamic acid caused a reversal of the metabolites, while concomitantly deactivating plasmalogen synthesis and mitochondrial β-oxidation of long chain saturated fatty acids pathways. These results indicate that the possible antidiabetic mechanism of cinnamic acid involves the enhancement of muscle glucose uptake, with concomitant suppression of redox imbalance and proteolysis, while improving purinergic activities and modulating glucose-lipid metabolism. Graphical Abstract: [Figure not available: see fulltext.]