NONRATT021972 long-noncoding RNA: A promising lncRNA in diabetes-related diseases

Figure 1. T2 DM, when treated with lncRNA NONRATT021972 siRNA, increases the insulin receptor substrate (IRS) 1 expression in superior cervical ganglia (SCG) whereas decreases the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), mRNA, P2X7, P2X3, GAFP, ERK1/2 expression in Dorsal Root Ganglion (DRG) while inhibiting the serine phosphorylation of IRS1 and activation of SGCs in the DRG. These results in the improvement of heart rate variable (HRV) while decreasing the excitability of DRG neuron which ultimately leads to the reduction of diabetic neuropathy and diabetic cardiac autonomic neuropathy.

Figure 2. MI Rat, when treated with siRNA, leads to the decrease in ck, ck-mb, LDH, AST enzymes, serum Epinephrine and Norepinephrine and the expression of P2X7 immunoreactivity, mRNA, protein, p38 MAPK, TNF-α, IL-6, TH/GAP43. Whereas the p-ERK1/2 expression in superior cervical ganglia (SCG) increases. It also leads to the inhibition of [Ca2+]i in oxygen and glucose deprived PC12 cells and BzATP-activated current in HEK293 cell. The systolic and diastolic blood pressure, heart rate, low-frequency (LF) power, and LF/HF ratio are normalized. These changes result in the prevention and reduction in pathophysiological processes mediated in stellate ganglia (SG) after Myocardial Infarction (MI), sympathetic neuronal injury induced by ischemia and abnormal changes in cardiac function after MI.

Figure 3. In T2 DM rats, where the Hepatic Glucokinase (HGK) is lower, the level of lncRNA NONRATT021972 is increased. These rats, when treated with siRNA NONRATT021972, leads to decrease in the p-GSK 3β protein and reduction in hyperglycemia whereas increase in p-AKT1 and Glucokinase (GK) expression. These are regulated by (PKB/AKT) signaling pathway activation and results in the improvement in the dysfunction of HGK.