Nonenzymatic Glycation of Transferrin: Decrease of Iron-Binding Capacity and Increase of Oxygen Radical Production.

Fujimoto, Sadaki; Kawakami, Naoko; Ohara, Akira

doi:10.1248/bpb.18.396

Cited by 42 publications

(25 citation statements)

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“…Our study differs from previously reported studies 13,[26][27][28][29][30][31] in certain aspects. .irst, the offspring group from parents with DM2 was carefully matched to healthy individuals as far as medical history, age, sex, BMI and WHR are concerned.…”

Section: Discussioncontrasting

confidence: 99%

Relative Iron "Overload" in Offspring of Patients with Type 2 Diabetes Mellitus: A New Component in the Conundrum of Insulin Resistance Syndrome?

Psyrogiannis

Kyriazopoulou²,

Symeonidis³

et al. 2003

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There are a few reports suggesting that subtle disturbances of iron metabolism are frequently found in patients with type 2 diabetes (DM2), but it is not known if these disturbances precede or accompany the diabetic state. We investigated the serum iron indices in 41 offspring of DM2 parents (group I) with normal glucose tolerance, and in 49 offspring whose parents had no history of DM2 and were matched for sex, age, body mass index (BMI), waist to hip ratio (WHR) and blood pressure (group II). Serum iron, ferritin, total iron binding capacity (TIBC), transferrin saturation, serum triglycerides, cholesterol, Apo-B, high density lipoprotein (HDL) and glucose and insulin values during an oral glucose tolerance test were measured. Insulin resistance was assessed using the homeostasis model assessment (HOMA -Insuline resistence index-IRI). In comparison to controls (group II), the offspring of DM2 subjects (group I) had higher fasting serum triglycerides (mean ± SD 2.25±2.08 vs. 1.6±0.8 mmol/L, p<0,05), lower HDL cholesterol (0.96 ± 0.2 vs. 1.1 ± 0.2 mmol/L, p<0.001), higher total cholesterol (5.5 ± 1.1 vs. 5.1 ± 0.8 mmol/L, p < 0.05), higher apo-B-lipoprotein (133.2±34.3 vs. 125.5±30.5 mg/dl, p<0.05), higher LDL-C (3.7 ± 0.8 vs. 3.2 ± 0.6 mmol/L), higher ã-GT (28±10 vs. 17±5.6 IU/L, p<0.01) higher insulin in the Area Under the Curve (204.7±140.8 v. 153.1 ± 63.0 ìU/ml, p<0.05) and higher ÇÏÌÁ-ÉRI (2.84±1.39 vs. 1.67±0.77, p<0.001), higher serum ferritin concentrations (98.3±57.7 vs. 62.0±41.1 ng/ml, p<0.01), higher serum iron concentration (20.2±6.0 ìmol/L vs. 14.5±4.3, p<0.001) and higher transferrin saturation index (31.3±8.4 vs. 22.6±7.3, p<0.0001). By single linear analysis in the offspring of DM2 parents, there was a positive correlation of IRI with transferrin saturation (r=0.400, p<0.01), fibrinogen (r=0.377, p=0.025) and ferritin concentration (r=0.344, p=0.041), and a negative correlation with TIBC (r=-0.477, p < 0.0001), while stepwise multiple regression analysis, IRI showed a positive correlation with fibrinogen (b=0.64, t=3.746, p<0.001), triglycerides (b=0.37, t=2.619, p<0.01) and ferritin (b=0.20, t=1.827, p=0.05). No correlation of IRI, with any of the above parameters was seen in the offspring of normal parents. By logistic regression analysis the parameters characterizing the offspring of parents with DM2 were IRI (OR 14.9 CI 2.4-91.0) serum iron (OR 44.2 CI 6.9-281), TIBC (OR 6.1 CI 1.01-37.0 and ã-GT (OR 29.6 CI 5.0-174). In conclusion, the data indicate that the iron load, is significantly increased in offspring of DM2 subjects with unaffected glucose tolerance. .urthermore, ferritin concentration is related to insulin resistance. Hence, the relative iron overload in offspring of type 2 diabetics is present along with insulin resistance and might worsen the hepatic insulin insensitivity already present in these patients.

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Section: Discussioncontrasting

confidence: 99%

Relative Iron "Overload" in Offspring of Patients with Type 2 Diabetes Mellitus: A New Component in the Conundrum of Insulin Resistance Syndrome?

Psyrogiannis

Kyriazopoulou²,

Symeonidis³

et al. 2003

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“…Since free metals are essential for the prooxidative effect, the question arises whether there are sufficient amounts of unbound metals in diabetic individuals to induce autooxidation of ascorbic acid. Glycation of proteins occurs in diabetes, and the binding capacity of transferrin to iron is reduced when this transport protein is glycated [68]. On the other hand, the relevance of glycation in vivo has been questioned [69].…”

Section: Discussionmentioning

confidence: 99%

Vitamin C supplementation of the maternal diet reduces the rate of malformation in the offspring of diabetic rats

1997

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Although improved metabolic control of maternal diabetes has reduced the rate of complications during pregnancy, the incidence of congenital malformations is still increased in children of insulin-dependent-diabetic (IDDM) mothers [1±4]. The mechanisms by which maternal diabetes disrupts embryonic development are not completely understood, but the risk of fetal malformation is strongly correlated to the maternal glucose concentration [2±4]. Maternal levels of triglycerides, b-hydroxybutyrate and branched chain amino acids are also of importance for the occurrence of fetal dysmorphogenesis [5]. In the embryo, disturbed metabolism of sorbitol, inositol, arachidonic acid and prostaglandins has been demonstrated in experimental diabetic pregnancy and Diabetologia (1997 Vitamin C supplementation of the maternal diet reduces the rate of malformation in the offspring of diabetic ratsDepartment of Medical Cell Biology, Uppsala University, Uppsala, SwedenSummary An excess of reactive oxygen species (ROS) has been associated with the increased rate of congenital malformations in experimental diabetic pregnancy. Previous in vitro and in vivo studies show that antioxidants can protect the embryonic development in a diabetic environment. In the present investigation we examined the antiteratogenic capacity of vitamin C, an antioxidative agent not previously evaluated as a dietary supplement in diabetic pregnancy. Normal and streptozotocin diabetic rats were either fed a standard diet or a diet enriched with 0.9, 1.8 or 4 % sodium ascorbate throughout pregnancy. On gestational day 20, the litters of normal and diabetic rats without vitamin C supplement contained 9 and 12 % early resorptions, 2 and 17 % late resorptions and 1 and 27 % malformations, respectively. Vitamin C treatment reduced the rates of late resorptions and malformations in the diabetic groups in proportion to the dose administered. Thus, in the diabetic group with 4 % ascorbate treatment we found unchanged numbers of early resorptions, but only 7 % late resorptions (p < 0.05 vs untreated diabetic pregnancy) and 8 % malformations (p < 0.05 vs untreated diabetic pregnancy). Maternal diabetes did not alter tissue levels of ascorbic acid in the fetuses at term, whereas vitamin C treatment caused accumulation of ascorbic acid in the placenta, maternal and fetal liver. Vitamin C supplementation yielded increased a-tocopherol concentration in the placenta and caused a reduction of the high concentrations of thiobarbituric acid reactive substances (TBARS) in serum of pregnant diabetic rats. Vitamin C treatment reduces the rates of congenital malformations and late resorptions, thereby supporting that ROS are involved in the embryonic dysmorphogenesis of diabetic pregnancy. [Diabetologia (1997 Keywords Diabetic pregnancy, streptozotocin, rat, embryo, fetus, congenital malformation, vitamin C, antioxidant therapy, TBARS, oxidative stress. Corresponding author: C. M. Sima Â n, Department of Medical Cell Biology, Uppsala University, Biomedicum, P. O. Box 571, S-751 23 Up...

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“…The current study also shows a similar increase of glycation of transferrin during poor glycemic control. An in vitro study (40) demonstrated that nonenzymatic glycation of transferrin decreases the iron binding capacity by binding the iron ions loosely on the protein and also increasing the production of free oxygen radicals including O 2 Ϫ and OH. The current study indicates potential pathological changes that occur in diabetes.…”

Section: ) Paired Analysis Showed a Significant Difference In Glycamentioning

confidence: 99%

Identification of Amadori-Modified Plasma Proteins in Type 2 Diabetes and the Effect of Short-Term Intensive Insulin Treatment

Jaleel

Halvatsiotis

Williamson³

et al. 2005

Diabetes Care

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OBJECTIVE -Growing evidence supports that nonenzymatic glycation products may cause hyperglycemia-induced diabetes complications. Amadori-modified proteins are the intermediate products of nonenzymatic glycation and constitute the forms of glycated proteins in diabetes.The objective of the current study was to utilize two-dimensional gel electrophoresis, Western blot, and mass spectrometry to identify Amadori-modified plasma proteins in type 2 diabetic patients with poor glycemic control and assess the impact of short-term insulin treatment on the glycation of these proteins.RESEARCH DESIGN AND METHODS -We compared eight type 2 diabetic subjects (aged 56 Ϯ 3 years and BMI 29.7 Ϯ 0.9 kg/m 2 ) with an average diabetes duration of 8.5 years (range 3-19) with equal numbers of weight-matched (aged 56 Ϯ 2 years and BMI 30.1 Ϯ 10.0 kg/m 2 ) and lean (aged 58 Ϯ 2 years and BMI 25 Ϯ 00.5 kg/m 2 ) nondiabetic subjects who have no first-degree relatives with diabetes. Two separate blood samples were collected from the type 2 diabetic subjects, one following 2 weeks of withdrawal of all antidiabetic medications (T 2 DϪ; plasma glucose 12.6 Ϯ 1.0 mmol/l) and another following 10 days of intensive insulin treatment (T 2 Dϩ; plasma glucose 5.5 Ϯ 0.2 mmol/l). Plasma proteins were separated using single and two-dimensional gel electrophoresis. Western blot analysis was performed, and several proteins, which reacted with the Amadori-antibody (1-deoxyfructosyl lysine), were identified by tandem mass spectrometry.RESULTS -No significant differences in the glycation of proteins between the obese and lean groups were noted, but type 2 diabetic patients had several proteins with higher glycation than the control groups. We identified 12 plasma proteins with reduced reaction to the anti-Amadori antibody upon intensive insulin treatment. A significant (P Ͻ 0.03) difference in Amadori modification was observed between the T 2 DϪ and control subjects for all these proteins except the Ig light chain. Insulin treatment reduced Amadori modification of albumin (23.2%, P Ͻ 0.02), fibrin (34.6%, P Ͻ 0.001), Ig heavy chain constant region (20.7%, P Ͻ 0.05), transferrin (25.4%, P Ͻ 0.04), and Ig light chain (13%, P Ͻ 0.02). In addition, Western blot analysis of two-dimensional gel electrophoresis identified ␣-fibrinogen precursor, ␤-fibrinogen precursor, fibrinogen ␥-B chain precursor, hemopexin, vitamin D binding protein, and serine protease inhibitor as proteins with a reduced reaction to anti-Amadori antibody upon intensive insulin treatment.CONCLUSIONS -The current approach offers the opportunity to identify Amadori modification of many proteins that may cause functional alterations and offers the potential for monitoring short-term glycemic control in diabetic patients. Diabetes Care 28:645-652, 2005H yperglycemia-induced advanced glycation end products (AGEs) are implicated as one of the main underlying mechanisms of chronic complications in diabetes (1-9). Nonenzymatic glycation reactions between extracellular proteins and glucose are one ...

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Nonenzymatic Glycation of Transferrin: Decrease of Iron-Binding Capacity and Increase of Oxygen Radical Production.

Cited by 42 publications

References 1 publication

Relative Iron "Overload" in Offspring of Patients with Type 2 Diabetes Mellitus: A New Component in the Conundrum of Insulin Resistance Syndrome?

Relative Iron "Overload" in Offspring of Patients with Type 2 Diabetes Mellitus: A New Component in the Conundrum of Insulin Resistance Syndrome?

Vitamin C supplementation of the maternal diet reduces the rate of malformation in the offspring of diabetic rats

Identification of Amadori-Modified Plasma Proteins in Type 2 Diabetes and the Effect of Short-Term Intensive Insulin Treatment

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