Does polyamine oxidase activity influence the oxidative metabolism of children who suffer of diabetes mellitus?

Diabetes mellitus is a metabolic disease characterized by inadequate secretion of insulin. Polyamine oxidase (PAO), a FAD-containing enzyme is involved in the biodegradation of Sp and Spd, catalyzing the oxidative deamination of Sp and Spd, resulting in production of ammonia (NH(3)), corresponding amino aldehydes and H(2)O(2). Malondialdehyde (MDA) and acrolein (CH2=CHCHO), potentially toxic agents, which induce oxidative stress in mammalian cells, are then spontaneously formed from aminoaldehydes. The main signs of oxidative stress in diabetic children were the values of HbA1c and MDA levels. Polyamines have an insulin-like action. Antiglycation property of spermine and spermidine has been recently confirmed. There are no data in the literature about plasma polyamine oxidase (PAO) activities in children with type 1 diabetes. The idea of this study was to evaluate the polyamine metabolism through the estimation of polyamine oxidase activity. We have study children with newly diagnosed type 1 diabetes mellitus (n = 35, age group of 5-16 years, as well as age-matched healthy control subjects (n = 25). The biochemical investigations were done on diabetic children who have the pathological values of glucose (9.11-17.33 mmol/l) and glycosylated Hb (7.57-14.49% HbA(1c)). The children in the control group have referent values of glucose and glycated hemoglobin (4.11-5.84 mmol/L and HbA(1c) 4.22-6.81% of the total Hb. Glucose levels in blood plasma and glycosylated hemoglobin in erythrocythes hemolysates (HbA1c) were measured by using standard laboratory methods. PAO activity in venous blood plasma and the amount of malondialdehyde (MDA) were measured by the spectrophotometric methods. PAO activity, glycemia, HbA1c and MDA were significantly increased in diabetic children compared to the control subjects. PAO activity in children with type 1 diabetes mellitus was very high. The findings of higher blood HbA(1C) and MDA levels confirm the presence of oxidant stress in children with type 1 diabetes mellitus and demonstrate that PAO activity may participate in these circumstances.

Altered degradation of circulating nucleic acids and oligonucleotides in diabetic patients.

Foreign, infection-associated or endogenously generated circulating nucleotide motifs may represent the critical determinants for the activation of the Toll-like receptors (TLRs), leading to immune stimulation and cytokine secretion. The importance of circulating nucleases is to destroy nucleic acids and oligonucleotides in the blood stream and during cell entry. Patients with juvenile insulin-dependent diabetes, adult patients with insulin-dependent diabetes and adult patients with type 2 diabetes were allocated to the study, together with the age-matched control subjects. Plasma RNase and nuclease activity were examined, in relation to different substrates-TLRs response modifiers, and circulating RNA and oligonucleotides were isolated. The fall in enzyme activity in plasma was obtained for rRNA, poly(C), poly(U), poly(I:C), poly(A:U) and CpG, especially in juvenile diabetics. In order to test the non-enzymatic glycation, commercial RNase (E.C.3.1.27.5) and control plasma samples were incubated with increasing glucose concentrations (5, 10, 20 and 50 mmol/l). The fall of enzyme activity was expressed more significantly in control plasma samples than for the commercial enzyme. Total amount of purified plasma RNA and oligonucleotides was significantly higher in diabetic patients, especially in juvenile diabetics. The increase in the concentration of nucleotides corresponded to the peak absorbance at 270 nm, similar to polyC. The electrophoretic bands shared similar characteristics between controls and each type of diabetic patients, except that the bands were more expressed in diabetic patients. Decreased RNase activity and related increase of circulating oligonucleotides may favor the increase of nucleic acid "danger motifs", leading to TLRs activation.