Acute Modulation of Toll-Like Receptors by Insulin

  1. Husam Ghanim, PHD,
  2. Priya Mohanty, MD,
  3. Rupali Deopurkar, MD, PHD,
  4. Ching Ling Sia, BSC,
  5. Kelly Korzeniewski, BSC,
  6. Sanaa Abuaysheh, BSC,
  7. Ajay Chaudhuri, MD and
  8. Paresh Dandona, MD
  1. From the Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York
  1. Corresponding author: Paresh Dandona, pdandona{at}kaleidahealth.org

Abstract

OBJECTIVE—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. We have now hypothesized that low-dose insulin infusion in obese type 2 diabetic patients suppresses TLR expression.

RESEARCH DESIGN AND METHODS—Ten type 2 diabetic patients were infused with a low dose of insulin (2 units/h) and dextrose to maintain normoglycemia for 4 h, while another 14 type 2 diabetic patients were infused with either dextrose or saline for 4 h and served as control subjects. Blood samples were collected before and at 2, 4, and 6 h. TLR expression was determined in mononuclear cells (MNCs).

RESULTS—Insulin infusion significantly suppressed TLR1, -2, -4, -7, and -9 mRNA expression in MNCs within 2 h of the infusion, with a maximum fall at 4 h 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 h. 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 h in MNCs. There was no change in TLR expression or DNA binding by PU.1 following dextrose or saline infusion in the control groups.

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

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 12 June 2008.

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted June 7, 2008.
    • Received March 19, 2008.
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This Article

  1. Diabetes Care vol. 31 no. 9 1827-1831
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