Research Highlights

doi:10.1038/nindia.2016.122 Published online 16 September 2016

Metformin, diet tweak to treat diabetic renal damage

Getting back to normal diet following a period of high fat diet (or diet reversal), along with intake of the oral diabetes medicine metformin, can reduce kidney damage associated with 'metabolic memory'1, according to a new study by scientists at the National Institute of Pharmaceutical Education and Research (NIPER), Mohali.

Benefits of strict glycaemic control can’t be harnessed soon after a period of poor glycaemic control — this phenomenon is called metabolic memory.

The researchers made rats insulin-resistant by feeding them a high fat diet (HFD) for 16 weeks. They found that switching the animals from HFD to normal diet for 8 weeks did not reverse glycaemia and renal complications. This showed that the metabolic memory of the rats persisted. The researchers then used diet reversal along with metformin treatment (100 mg per kg weight per day). This weakened the metabolic memory-associated renal damage in short-duration of 8 weeks. 

Earlier, they had shown that diet reversal for 4 weeks could not reduce the vascular dysfunction brought about by 12 weeks of HFD feeding2

The researchers detected HFD-induced insulin resistance and renal damage through decreased adenosine monophosphate-activated protein kinase (AMPK); increased inflammatory markers-COX-2, IL-1β; fibrosis and its markers-collagen, fibronectin, α-SMA and apoptotic markers-PARP, Caspase 3. These parameters could not be reversed by short term diet reversal alone.

"However, diet reversal along with metformin treatment does weaken metabolic memory," says lead researcher Kulbhushan Tikoo.


References

1. Tikoo, K. et al. Metformin improves metabolic memory in high fat diet (HFD)-induced renal dysfunction. J. Biol. Chem. (2016) doi: 10.1074/jbc.C116.732990


2. Tallapragada, D. S. et al. Long-lasting partnership between insulin resistance and endothelial dysfunction: role of metabolic memory. Brit. J. Pharmacol. 172, 4012-4023 (2015) doi: 10.1111/bph.13145