Desensitization insulin

Knockout mice have been reported for several FATPs [1]. As insulin desensitization has been closely linked to excessive fatty acid uptake and intracellular diacylgly-cerol and TG accumulation, these animal models were particularly evaluated in the context of protection from diet-induced type 2 diabetes ( Type 2 Diabetes Mellitus (T2DM)). In addition, studies on human subjects have also established genetic links between polymorphisms in FATP genes and metabolic alterations [1]. 

Insulin Desensitization Insulin Receptor Insulin Resistance Insulin Secretagogues Insulin-like Growth Factor Integrase Integrin, a 4(31 Integrin, a 4(3 7 Integrin, a IIb(3 3... 

Eapen SS, Connor EL, Gern JE. Insulin desensitization with insulin lispro and an insulin pump in a 5-year-old child. Ann Allergy Asthma Immunol 2000 85(5) 395-7. 

Occasional patients have antibodies to injected insulin, but the significance of the antibodies is minimal. Human insulin therapy has not totally eliminated insulin allergies, although most patients have a local reaction that will dissipate over time. If the allergic reaction does not improve or is systemic, insulin desensitization can be carried out. Protocols for desensitization are available from major insulin manufacturers. While more common in the animal insulin era, lipohypertrophy is still seen in some patients with longstanding type 1 DM. Such patients give their insulin injections in the same site to minimize discomfort. Because insulin absorption from an area of lipohypertrophy is unpredictable, avoidance of injections into these areas is mandatory. 

Allergic reactions to insulin include erythema, pruritus, and indurations,22 which usually are transient. For the more troublesome reactions, treatment options include dexamethasone, desensitization, or change in delivery system (i.e., insulin pump or inhaled insulin). 

The response to many polypeptide hormones also diminishes with chronic stimulation, but the time course is much longer (many hours to days) and the mechanism is different from that involved in desensitization. Binding of insulin, calcitonin, LH, TRH, and EGF to their respective receptors promotes a physiological response but ultimately leads to the clearance of these receptors from the surface and a blunting of that response. The hormone-mediated loss... 

Yokoyama H, Fukumoto S, Koyama H, Emoto M, Kitagawa Y, Nishizawa Y. Insulin allergy desensitization with crystalline zinc-insulin and steroid tapering. Diabetes Res Clin Pract 2003 61 161-6. 

Frigerio C, Aubry M, Gomez F, Graf L, Dayer E, de Kalbermatten N, Gaillard RC, Spertini F. Desensitization-resistant insulin allergy. Allergy 1997 52(2) 238-9. 

Maechler, P., Kennedy, E. D., Wang, H., and Wollheim, C. B., 1998, Desensitization of mitochondrial Ca2+ and insulin secretion responses in the beta cell, J. Biol. Chem. 273, pp. 20770-20778 Masubuchi, Y., Nakayama, S., and Horie, T., 2002, Role of mitochondrial permeability transition in diclofenac-induced hepatocyte injury in rats, Hepatology 35, pp. 544-551 Masubuchi, Y., Suda, C., and Horie, T., 2005, Involvement of mitochondrial permeability transition in acetaminophen-induced liver injury in mice, J. Hepatol. 42, pp. 110-116 Mathai, J.P., Germain, M., Marcellus, R. C., and Shore, G. C., 2002, Induction and endoplasmic reticulum location of BIK/NBK in response to apoptotic signaling by E1A and p53, Oncogene 21, pp. 2534-2544... 

Treatment of these problems is by substituting another insulin species which does not cross-react with the antibodies, by desensitization, or by local or systemic administration of glucocorticoids. If a severe allergic reaction occurs, the drug has to be discontinued and the patient treated with the usual agents (e.g. adrenaline, antihistamines or corticosteroids). Patients who have experienced severe systemic allergic symptoms should be skin-tested with another insulin preparation before its initiation. Desensitization procedures may permit resumption of insulin administration. 

Variations in the pharmacokinetics of the sulphonylureas are clinically relevant because of the differences in their rate of onset and their duration of action. Differences in the rate of onset are important because they relate to the capacity to reduce the delay in acute insulin release after nutritional challenge and therefore their capacity to reduce the evaluation and prolongation of the postprandial hyperglycaemia. Differences in the duration of action are important because they relate to the risk of causing chronic hyperin-sulinaemia, long-lasting hypoglycaemia, and possibly desensitization to sulphonylureas (Melander et al., 1990). 

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