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Immunological effects of a hyperinsulinaemic euglycaemic insulin clamp in healthy males
M Kappel1, F Dela, T Barington
1The Copenhagen Muscle Research Centre, Department of Infectious Diseases, Rigshospitalet, National University Hospital, Denmark.
Insights
Supraphysiological insulin levels boost natural killer (NK) cell activity in humans, enhancing their cytotoxic capabilities. However, these high insulin concentrations also reduce the numbers of NK cells, lymphocytes, and monocytes, suggesting a complex immune response.
Area of Science:
- Immunology
- Endocrinology
- Human Physiology
Background:
- Insulin is a key metabolic hormone with known effects on various cellular functions.
- The direct impact of varying insulin concentrations on the human immune system, particularly natural killer (NK) cells, remains incompletely understood.
Purpose of the Study:
- To investigate the in-vivo and in-vitro effects of physiological and supraphysiological insulin concentrations on the human immune system.
- To determine how insulin affects NK cell activity, lymphocyte counts, and monocyte populations.
Main Methods:
- Ten healthy males underwent a two-step hyperinsulinemic euglycemic clamp to achieve controlled plasma insulin levels.
- Blood mononuclear cells (BMNCs) were analyzed for NK cell activity, cell percentages (CD16+, CD14+, HLA-DR+, CD45RO+), and counts.
- In-vitro assays assessed insulin's effect on NK cell activity and BMNC proliferation.
Main Results:
- Supraphysiological insulin levels significantly increased unstimulated NK cell activity per cell.
- A decline in the absolute numbers of monocytes, lymphocytes, and specific immune cell subsets (CD16+, CD14+, HLA-DR+, CD45RO+) was observed at high insulin concentrations.
- No significant changes were noted in lymphocyte subset percentages or immunoglobulin-secreting cell numbers.
Conclusions:
- Supraphysiological hyperinsulinemia enhances individual NK cell cytotoxic activity but reduces the overall number of lymphocytes and monocytes.
- These findings suggest a potential insulin-induced immune modulation, although clinical relevance may be limited.
- Further research is warranted to elucidate the precise mechanisms and clinical implications of insulin's immunomodulatory effects.
Abstract:
The purpose of this study was to determine the in-vivo and in-vitro effects of insulin, at physiological and supraphysiological concentrations, on the human immune system. Ten healthy young men went through a sequential two-step hyperinsulinaemic euglycaemic clamp. Plasma insulin concentrations were increased from baseline (9.0 microU/ml) to 49.1 microU/ml after 1 h of insulin infusion (step I) and to 1281 microU/ml (step II) after 2 h of infusion. As control experiments infusions of isotonic saline were performed. The unstimulated natural killer (NK) cell activity among blood mononuclear cells (BMNC) increased in response to supraphysiological plasma insulin levels (baseline versus step II: 20.6 +/- 11.3 versus 27.8 +/- 14.4%). The percentages of the D16+ NK cells did not change, indicating an enhanced cytotoxic capability per individual NK cell. Insulin also slightly increased the activity of NK cells in vitro. A decline at step II in the concentrations of monocytes (0.29 +/- 0.09 versus 0.12 +/- 0.03 x 10(9)/L), lymphocytes (1.57 +/- 0.46 versus 1.22 +/- 0.25 x 10(9)/L), and CD16+(24.2 +/- 17.5 versus 16.7 +/- 11.2 x 10(7)/L), CD14+ (20.9 +/- 10.8 versus 8.6 +/- 3.9 x 10(7)/L), HLA-DR+ (37.2 +/- 22.1 versus 19.2 +/- 10.7 x 10(7)/L) and CD45RO+ (91.6 +/- 33.4 versus 61.7 +/- 6.4 x 10(7)/L) cells as well as in the percentages of CD14+ cells (11.2 +/- 4.7 versus 6.4 +/- 2.3%) and CD14+/HLA-DR+ monocytes (9.7 +/- 3.9 versus 4.8 +/- 2.8%) were observed. No changes were found at step I. Hyperinsulinaemia did not change the percentages of the CD3+, CD4+, CD8+, CD19+, CD56+, CD11a+, CD45RO+ and CD45RA+ cells, the numbers of circulating immunoglobulin (Ig)G-, IgA- and IgM- secreting cells, or the proliferative responses of BMNC to phytohaemagglutinin, purified derivative of tuberculin or interleukin (IL)-2. Hyperinsulinaemia did not change the in-vitro sensibility to insulin. In conclusion, supraphysiological insulin levels increased the activity of the individual NK cells, but decreased the numbers of NK cells, lymphocytes and activated monocytes. The findings are presumably of minor clinical relevance but may indicate an insulin-induced immune activation.