Background

Glucose and lipid abnormalities, oxidative stress (OXS) and reduced brain-derived neurotrophic factor (BDNF) are involved in cognitive dysfunction in diabetes. Glucagon like peptide 1 (GLP1) receptors modulate glucose and lipid metabolism, cognitive function and serum osteocalcin. On the other hand, osteocalcin modulates cognitive function and glucose and lipid metabolism. This study investigated whether the GLP 1 agonist liraglutide improves cognitive function via modulation of serum osteocalcin and glucose and lipid metabolism.

Methods

Effects of 4 weeks liraglutide treatment (100 µg/Kg/d and 300 µg/Kg/d) on changes in cognitive function and bone homeostasis, induced by high fat diet/low-dose streptozotocin (HFD-STZ), were determined in rats. Cognitive function was assessed using Morris water maze (MWM) test. Serum and bone biochemical parameters were determined.

Results

Liraglutide dose-dependently improved cognitive function in diabetic rats (reduced escape latency, and increased time spent in target quadrant in MWM test, compared to diabetic control). Glucose and lipid abnormalities and the associated changes in serum BDNF and oxidative stress makers were improved. Serum BDNF and glutathione were significantly increased, whereas malondialdehyde level was reduced. Serum osteocalcin was significantly increased and correlated with improvement in cognitive dysfunction. Serum and bone receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin ratios were significantly reduced by liraglutide treatment.

Conclusion

Improvement of cognitive dysfunction by liraglutide involves modulation of glucose and lipid metabolism and serum osteocalcin. GLP1 agonists may provide an alternative metabolic approach for cognitive dysfunction in diabetes.