Abstract

Background: Low dose insulin infusion has been shown to exert a prompt and powerful anti-inflammatory effect. Toll like receptors (TLRs) are major determinants of the inflammatory response to viral and bacterial pathogens.

Hypothesis: We have now hypothesized that low dose insulin infusion in obese type 2 diabetic patients (T2DM) suppresses TLRs expression.

Methods: Ten T2DM were infused with a low dose of insulin (2 Units/hr) and dextrose to maintain normoglycemia for 4 hours while another 14 T2DM were infused with either dextrose or saline for 4 hours and served as controls. Blood samples were collected before and at 2, 4 and 6 hours TLRs expression was determined in MNC.

Results: Insulin infusion significantly suppressed TLR1, 2, 4, 7 and 9 mRNA expression in MNC within 2 hours of the infusion with a maximum fall at 4 hours by 24±9%, 21±5%, 30±8%, 28±5% and 27±10%, (P<0.05, for all) respectively, below the baseline. TLR2 protein was suppressed by 19±7% (P< 0.05) below the baseline at 4 hours. The DNA binding of PU.1, a major transcription factor regulating many TLR genes was concomitantly suppressed by 24±10% (P<0.05) by 4 hours in the MNC. There was no change in TLRs expression or DNA binding by PU.1 following dextrose or saline infusion in the control groups.

Conclusion: Insulin suppresses the expression of several TLRs, at the transcriptional level possibly through its suppressive effect on PU.1.