Insulin Therapy of Nondiabetic Septic Patients Is Predicted by para-Tyrosine/Phenylalanine Ratio and by Hydroxyl Radical-Derived Products of Phenylalanine

Szilárd Kun, Gergő A Molnár, Eszter Sélley, Lívia Szélig, Lajos Bogár, Csaba Csontos, Attila Miseta, István Wittmann, Szilárd Kun, Gergő A Molnár, Eszter Sélley, Lívia Szélig, Lajos Bogár, Csaba Csontos, Attila Miseta, István Wittmann

Abstract

Hydroxyl radical converts Phe to para-, meta-, and ortho-Tyr (p-Tyr, m-Tyr, o-Tyr), while Phe is converted enzymatically to p-Tyr in the kidney and could serve as substrate for gluconeogenesis. Pathological isoforms m- and o-Tyr are supposed to be involved in development of hormone resistances. Role of Phe and the three Tyr isoforms in influencing insulin need was examined in 25 nondiabetic septic patients. Daily insulin dose (DID) and insulin-glucose product (IGP) were calculated. Serum and urinary levels of Phe and Tyr isoforms were determined using a rpHPLC-method. Urinary m-Tyr/p-Tyr ratio was higher in patients with DID and IGP over median compared to those below median (P = 0.005 and P = 0.01, resp.). Urinary m-Tyr and m-Tyr/p-Tyr ratio showed positive correlation with DID (P = 0.009 and P = 0.023, resp.) and with IGP (P = 0.004 and P = 0.008, resp.). Serum Phe was a negative predictor, while serum p-Tyr/Phe ratio was positive predictor of both DID and IGP. Urinary m-Tyr and urinary m-Tyr/p-Tyr, o-Tyr/p-Tyr, and (m-Tyr+o-Tyr)/p-Tyr ratios were positive predictors of both DID and IGP. Phe and Tyr isoforms have a predictive role in carbohydrate metabolism of nondiabetic septic patients. Phe may serve as substrate for renal gluconeogenesis via enzymatically produced p-Tyr, while hydroxyl radical derived Phe products may interfere with insulin action.

Figures

Figure 1
Figure 1
Chromatograms of a standard (STD), a serum (SE), and a urine sample of a septic patient (U). p-Tyr, para-tyrosine; m-Tyr, meta-tyrosine; o-Tyr, ortho-tyrosine; Phe, phenylalanine.
Figure 2
Figure 2
Urinary m-Tyr/p-Tyr ratio in septic patients requiring insulin administration, according to (a) daily insulin dose or (b) insulin-glucose product. #P = 0.005 versus DID < median; ##P = 0.01 versus IGP < median. DID, daily insulin dose; IGP, insulin-glucose product.
Figure 3
Figure 3
Correlation of urinary m-Tyr concentration with (a) DID and (c) IGP. Correlation of urinary m-Tyr/p-Tyr ratio with (b) DID and (d) IGP in septic patients requiring insulin administration. DID, daily insulin dose; IGP, insulin-glucose product.

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