The relationship between of ACE I/D and the MTHFR C677T polymorphisms in the pathophysiology of type 2 diabetes mellitus in a population of Brazilian obese patients

ABSTRACT Objectives This study aimed to evaluate the frequencies of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms in obese patients with and without type 2 diabetes mellitus (T2DM). Subjects and methods These polymorphisms were analyzed by polymerase chain reaction in 125 patients with obesity, 47 (T2DM) and 78 (Control Group). Results No significant difference was found on comparing the T2DM and Control Groups in respect to the genotypic frequencies of the polymorphisms - (II: 13.3% vs. 12.0%; ID: 37.8% vs. 37.3; DD: 48.9% vs. 50.7%; CC: 36.2% vs. 39.0%; CT: 46.8% vs. 49.3%; TT: 17.0% vs. 11.7%), and alleles (I: 32.2% vs. 30.7%; D: 67.8% vs. 69.3%; C: 59.6% vs. 63.6%; T: 40.4% vs. 36.4%) and their synergisms in the pathophysiology of T2DM. On analyzing the T2DM Group, there were no significant differences in the presence of complications. In this population of Brazilian obese patients, no correlation was found between the ACE and MTHFR polymorphisms in the development of T2DM. Conclusion Analyzing only the group with diabetes, there was also no relationship between these polymorphisms and comorbidities.

Xanthine oxidase activity in patients with age-related cataract associated with hypertension

Reactive oxygen species and lipid peroxidation are important factors that contribute to the development of age-related cataract. The study included 130 patients with age-related cataract, 69 of whom were diagnosed with hypertension (HT), 20 with hypertension and type 2 diabetes mellitus (DM), and 41 had no accompanying condition. The following parameters were measured in the serum of the examinees: products of lipid peroxidation malondialdehyde (MDA) and lipofuscin-like fluorophores (LLF), activity of prooxidative enzymes xanthine oxidase (XO) and myeloperoxidase (MPO), antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), the concentration of thiol groups, and the ferric reducing activity of plasma. The activity of prooxidative enzymes XO and MPO was higher in the plasma of patients with HT (XO=9.0±1.2 U/L; MPO=77.3±8.4 U/L) and with HT and DM (XO=11.9±0.9 U/L; MPO=89.5±5.0 U/L) compared to patients with age-related cataract (XO=6.2±0.9 U/L; MPO=52.4±6.3 U/L; P<0.01). Our research has shown that patients with age-related cataract and hypertension were exposed to increased oxidative damage of biomolecules, based on the increased plasma LLF and MDA content and decreased levels of thiol groups. Oxidative changes of biomolecules in these patients were associated with increased activity of the XO, MPO, and GPx enzymes and a lower extracellular SOD activity and total ferric reductive ability of plasma.

Erythrocyte plasma membrane redox system in first degree relatives of type 2 diabetic patients

Diabetes mellitus [TDM] is strongly associated with oxidative stress. Human erythrocytes contain a plasma membrane redox system [PMRS] which transfers electrons from intracellular donors [NADH, ascorbate] to extracellular acceptors outside the cell. We show that the activity of erythrocyte PMRS and APR reductase becomes elevated in first degree relatives of type 2 diabetics and in TDM subjects. The increase in PMRS and APR reductase signifies compensatory mechanisms to mitigate increased oxidative stress. These findings show that an impaired redox balance may be a cause the disturbance of homeostasis in type 2 diabetic families, even before the development of the disease

Type 2 diabetes mellitus: phylogenetic motifs for predicting protein functional sites.

Diabetes mellitus, commonly referred to as diabetes, is a medical condition associated with abnormally high levels of glucose (or sugar) in the blood. Keeping this view, we demonstrate the phylogenetic motifs (PMs) identification in type 2 diabetes mellitus very likely corresponding to protein functional sites. In this article, we have identified PMs for all the candidate genes for type 2 diabetes mellitus. Glycine 310 remains conserved for glucokinase and potassium channel KCNJ11. Isoleucine 137 was conserved for insulin receptor and regulatory subunit of a phosphorylating enzyme. Whereas residues valine, leucine, methionine were highly conserved for insulin receptor.Occurrence of proline was very high for calpain 10 gene and glucose transporter.

The role of AMP kinase in diabetes.

Type 2 diabetes is characterized by abnormal metabolism of glucose and fat, due in part to resistance to the actions of insulin in peripheral tissues. If untreated it leads to several complications such as blindness, kidney failure, neuropathy and amputations. The benefit of exercise in diabetic patients is well known and recent research indicates that AMP activated protein kinase (AMPK) plays a major role in this exercise related effect. AMPK is considered as a master switch regulating glucose and lipid metabolism. The AMPK is an enzyme that works as a fuel gauge, being activated in conditions of high energy phosphate depletion. AMPK is also activated robustly by skeletal muscle contraction and myocardial ischaemia, and is involved in the stimulation of glucose transport and fatty acid oxidation produced by these stimuli. In liver, activation of AMPK results in enhanced fatty acid oxidation and decreased production of glucose, cholesterol, and triglycerides. The two leading diabetic drugs namely, metformin and rosiglitazone, show their metabolic effects partially through AMPK. These data, along with evidence from studies showing that chemical activation of AMPK in vivo with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) improves blood glucose concentrations and lipid profiles, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes and other metabolic disorders.

Biochemical analysis of serum panceratic amylase and lipase enzymes in patients with type1 and type2 diabetes mellitus

To examine the pancreatic exocrine insufficiency in patient with diabetes mellitus by estimating serum pancreatic amylase and lipase enzymes in healthy subjects and in type 1 and type 2 diabetic patients. The study was conducted on 20 normal healthy volunteers and 39 diabetic patients referred to Al-Isra Medical Laboratory, Amman, Jordan during the period from April - November 2003 after recording their age and gender. The age of onset of diabetes and the type of treatment were determined and the patients were categorized into type 1 and type 2 diabetics. Blood samples were collected and analyzed for fasting blood sugar [FBS], glycosylated hemoglobin [HbA1C], serum insulin, and serum pancreatic amylase and lipase enzymes. All biochemical tests were carried out in the medical laboratories of Islamic Hospital, Amman, Jordan. All estimates were presented as means +/- SD, and statistical treatment of data were performed using student t-test. The FBS and HbA1C estimates were consistently higher in type 1 and type 2 diabetic patients, while no significant changes were observed in the estimates of serum insulin between the normal and diabetic patients. The reduction in serum pancreatic amylase was recorded in both types of diabetes, which amounted to 71% for type 1 diabetics and 49% for type 2 diabetics. On the other hand, reduction in serum lipase was only detected in type 1 diabetics amounting to 31%. Correlation of the reduction in serum amylase and lipase levels with the duration of disease revealed a remarkable decrease in both enzymes in patients with long-standing disease [76% and 39%] in type 1 diabetic patients. Whereas, patients with very low serum insulin estimates the reduction in serum amylase was 77% while serum lipase level was reduced by 42%. Similarly, the reduction in serum amylase in type 2 diabetes was higher in patients with longer duration of illness [59%] and in patients with low serum insulin value [79%], while reduction in serum lipase was only detected in patients with very low serum insulin [34%]. No differences in all measured parameters between males and females were recorded in type 1 and type 2 diabetics. Although most of diabetic research has been focused on dyslipidemia as a major risk factor for cardiac, cerebral and renal complications, the present study clearly illustrates an impairment of pancreatic exocrine function in type 1 and type 2 diabetes. We suggest that analysis of serum pancreatic enzymes could be an additional informative parameter for the assessment of chronicity and progress of the illness as well as the response to therapy

Angiotensin converting enzyme gene polymorphism in healthy Thais and patients with non-insulin dependent diabetes mellitus.

Insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene has been shown to be associated with various cardiovascular disorders in diabetic and non-diabetic patients. Its association with the development of non-insulin dependent diabetes mellitus (NIDDM) has been raised. This study was aimed to examine I/D polymorphism of ACE gene in healthy Thai subjects and patients with NIDDM. The I/D ACE genotypes were determined by polymerase chain reaction technique. Healthy unrelated subjects were 151 males and 147 females, 17-70 year old (mean +/- SD = 37.5 +/- 10.4). The unrelated diabetic patients were 42 males and 66 females, 20-79 years of age (mean +/- SD = 54.7 +/- 12.0). In healthy subjects, the ACE genotypes were DD 10.1 per cent, ID 39.2 per cent and II 50.7 per cent. Diabetic patients had similar distribution of ACE genotypes. The frequency of I and D alleles in diabetic patients was 0.69 and 0.31, similar to 0.70 and 0.30, respectively, in healthy subjects (p = 0.69). The frequency of I and D alleles in healthy Thai subjects was similar to the Japanese (I = 0.66 & D = 0.34) but different from Caucasians (I = 0.44-0.46 & D = 0.54-0.56). We conclude that I/D ACE gene polymorphisms may possess a racial difference. The similar frequency of both alleles in diabetic patients and healthy subjects suggests that there is no association between I/D polymorphism of ACE gene and diabetes mellitus in Thai individuals.

Plausible involvement of extralysosomal proteinase in derangement of leucocytic Ca2+/Mg2+ ATPase in diabetes.

Translocation of calcium activated neutral proteinase from cytosol to plasma membrane, concurrently with decrease in the activity of membrane bound Ca2+/Mg2+ ATPase has been detected in diabetic polymorphonuclear leucocytes. Plausible involvement of the extralysosomal proteinase in the derangement of the Ca2+/Mg2+ ATPase is indicated by non restoration of the enzyme activity on treatment with activators such as trypsin or calmodulin and enhanced membrane translocation of the proteinase observed with concomitant decrease in the activity of Ca2+/Mg2+ ATPase in normal neutrophils on insult with diabetic serum factor.

Actividad de la glucosa-6-fosfato deshidrogenasa en pacientes diabéticos tratados con pirofosfato de tiamina o cocarboxilasa / Activity of clucose-6-phosphate dehydrogenase on diabetic patients treated with thiramine pyrophosphate or cocarboxilase

Trabajos realizados con anterioridad tanto a nivel clínico como experimental en el Instituto de Investigaciones Cientificas Hans Selye, permiten proponer que la cocarboxilasa o pirofosfato de tiamina (PPT) estable en solución, al aplicarse a pacientes con hiperglucemia, mejora la incorporación de la glucosa a los tejidos. Con base en tales hechos, un posterior estudio pretende analizar si el PPT ejerce acción alguna sobre el ciclo de las pentosas. Para demostrar esto, se estudió la conducta de la glucosa-6-fosfato deshidrogenasa (G-6-PD) en el eritrocitos humanos, toda vez que su actividad se ha encontrado disminuida en los pacientes afectados por diabetes mellitus. Para comprobarlo se seleccionaron 10 pacientes de uno y otro sexo, de 45 a 70 años de edad y con diagnóstico de diabetes tipo II. De cada uno se tomó una muestra sanguínea antes de iniciar el traqtamiento con PPT y posteriormente a los 15, 30, 60, 90 y 120 días después de obtener la primera muestra, a fin de determinar la actividad de G-6-PD, así como las de glucosa, colesterol total, HDL, LDL, triglicériados y hemoglobina glucosilada. Los resultados obtenidos demuestran que la glucemia tiende a registrar niveles normales, alcanzando una recuperación física plena en 70 por ciento de los pacientes; en 100 por ciento de ellos también se normalizaron los niveles de colesterol y de triglicéridos. La hemoglobina glucosilada disminuye considerablemente en relación con los valores registrados antes de iniciar el tratamiento. Con respecto a la actividad de la G-6-PD, los autores observaron que ésta se incrementa, en promedio, de 3 a 5 U/g de hemoglobina en los pacientes hiperglucémicos: el máximo incremento de actividad se registra entre el segundo y tercer mes de tratamiento, lo cual indica que PPT participa en: 1) la incorporación de glucosa al interior de los eritrocitos, toda vez que dicha sustancia disminuye la glucosa sérica: 2) la utilización de la glucosa en el metabolismo de esta célilas, y 3) el ciclo de las pentosas, dado que la actividad de la G-6-PD aumenta en forma considerable.

Serum zinc and zinc containing enzymes in diabetes mellitus.

Serum zinc and levels of certain zinc containing enzymes like 'lactate dehydrogenase, malate dehydrogenase, alkaline phosphatase and serum insulin were studied in twenty five normal and fifty non insulin dependent diabetics. Zinc estimation was done bp atomic absorption spectrophotometry, insulin by radioimmunoassay and the enzymes by kinetic method. The non insulin dependent diabetic individuals showed significant hypozincaemia (P less than 0.001) associated with significant increase in serum insulin and lactate dehydrogenase level (P less than 0.001). Malate dehydrogenase level was markedly decreased (P less than 0.001). There was no significant variation in serum total proteins, creatinine and alkaline phosphatase levels.