It has been well known for decades already, that immune cells also have insulin receptors, which to me turns out most obvious, as "these cells need to eat as well as anyother". They certainly need to incorporate and use glucose for their normal methabolism, so any alteration of Glucose / Insulin balance can affect their functioning as it does with the rest of the somatic and visceral cells. In fact, steroids for instance, influence this balance and in part, I think they should be held responsable for their effect on celular immune regulation. It is obvious that on systemic basis analysis, the physiological status of a severely uncompensated diabetic patient with hiperinsulinemia in response to hyperglycemia, hyperosmolarity, dehydration and keto-acidosis, affects all homeostatic balance including that of lymphoreticular and bone marrow organs and systems.

Old in vitro experiments have approached "the nutritional and methabolic needs of lymphoyd and mononuclear cells".

Best regards,

Juan C. Bertoglio./

PS: I had forgotten to add, that in insulin resistance conditions associated to methabolic syndrome, there is a systemic unhealthy chronic inflammatory status that also overdemands and stresses immune cells and their Regulatory pathways triggering damage on vascular endothelium.

Could we have the url? It is known for most who are into stress field research that the immune system is closely related with the stress system (http://www.ncbi.nlm.nih.gov/pubmed/10415589). This means that in case of acute stress, there will be a sudden boost of the immune system action and the opposite goes, in case of chronic stress (http://www.ncbi.nlm.nih.gov/pubmed/22727761). Moreover, we know now that in case of stress system activation, there will be hypercortisolemia, even temporary. Conclusively, due to the fact that cortisol opposes to insulin action, there will be a downregulation for insulin receptors, but overall, there will be hyperinsulinemia, leading to insulin resistance. Diabetic patients also exhibit high ROS concentrations, and thus, increased oxidative stress. So, it may be an epiphenomenon. May I have the url, of the paper you mentioned, just to understand exactly, what you mean?

I agree with Dr Bergoglio however insulin has been shown to have anti inflammatory properties in animal studies. In fact in sepsis one of the key issues is to regulate glucose metabolism and indirectly insulin effects, concentration and/or resistance. Be careful with the conclusion that cortisol recall the axis pitutitary adreno renal and its sistemic effects.

regards,

having recognized that all cells including immune cells have insulin receptors needed for glucose uptake, may I ask just how diabetes results in an immunodeficiency disorder?how does it shut down the immune system?

Dear Dr Simiiyu I would not consider it an immunodeficiency rather a costimulatory effect. Recall that, in the old times, serum free media contained ferritin and insulin and the results of cell activation were similar as compared with complete media. In addition, if you add insulin to the cell incubated with complete media no major effects are observed. We used to do mixed lymphocyte culture for 7 days and insulin did not decrease cytotoxicity.

regards,

Thank you very much again Dr. de Sanctis (muchas gracias desde el sur de Chile) for your new information on this interesting topic. Also, to our colleague Dr. Simiyu.

To this respect and in contrast to in vitro data, it is worth remembering here, the in vivo clinical situation in diabetes and sepsis (particularly with Gram (-) bacteria / endotoxins), where persistence of infection results in uncontrolled hyperglycemia with extraordinary elevated insulin requirements while affecting granulocytes and lymphocytes response. So in patients, hyperglycemia and hyperinsulinemia go together, and also with hydro-electrolytic, blood pH and ketones unbalance. Therefore, the clinic is not a clean and one variable at the time experiment. This phenomenon can also be seen in the control of local Gram (+) infections (such as streptococcal cellulitis) in diabetics, who suffer sudden and overwhelming spread of this infection with low immune reaction, and again, associated to uncontrolled hyperglycemia with extraordinary elevated insulin requirements.

But which is first, ¿ the egg or the hen ? – I think that question will be still giving long term employment to all of us… !!

Best,

Dear Dr. Stefanaki:

Please accept my apologies for not replying back to you earlier regarding your URL request, but I have gone over old work and looked for those papers dated back to 1983-84 but unsuccessfully, as they are not available in digital format and their printed versions are now in library storage and neither have the personal copies I first mentioned.

Nevertheless, I found this one from 1977 by B. Eriksson and E. Hedfor. The Effect of Adrenaline, Insulin and Hydrocortisone on Human Peripheral Blood Lymphocytes Studied by Cell Surface Markers. Scandinavian Journal of Haematology. Article first published online: 24 APR 2009. DOI: 10.1111/j.1600-0609.1977.tb02081.x

Meantime, here I copy and paste the summary for you:

“ Changes in numbers of peripheral blood lymphocytes from healthy individuals were calculated from samples collected before and after parenteral administration of adrenaline, insulin and hydrocortisone, respectively. A marked increase in circulating lymphocytes was noted in response to adrenaline and insulin. However, subpopulation analysis showed a decrease in the proportion of T-lymphocytes, estimated as cells forming rosettes with sheep red blood cells after incubation in the cold and a corresponding increase in proportion of lymphocytes having receptors for C3 (non-T lymphocytes). In contrast, lymphocyte numbers were unaffected by hydrocortisone. The results indicate that a decreased proportion of circulating T-lymphocytes and an increase of non-T lymphocytes may be the result of adaptive changes in response to various forms of stress and hence is to be expected in several clinical conditions”.

And also this other one…

J H Helderman. Acute regulation of human lymphocyte insulin receptors. Analysis by the glucose clamp. J Clin Invest. 1984 October; 74(4): 1428–1435. doi: 10.1172/JCI111554

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC425311/

I hope these two clasic ones turn out interesting and useful to you.

Best,