Vitamin K2 alleviates type 2 diabetes in rats by induction of osteocalcin gene expression.

OBJECTIVES: The biological mechanisms behind the association between vitamin K (Vit K) and glucose metabolism are uncertain. We aimed to analyze the expression of insulin 1 (Ins 1), insulin 2 (Ins 2) and cyclin D2, the expression of adiponectin and UCP-1 . In addition, we aimed to estimate the doses of Vit K2 able to affect various aspects of glucose and energy metabolism in type 2 diabetes. METHODS: Thirty adult male rats were allocated equally into five groups: control group, diabetes mellitus group, and groups 3, 4, and 5, which received Vit K2 at three daily dose levels (10, 15, and 30 mg/kg, respectively) for 8 wk. At the end of the study, blood samples were collected to quantify total osteocalcin, fasting plasma glucose, fasting insulin, and relevant variables. The expression of OC, Ins 1, Ins 2, cyclin D2, adiponectin, UCP-1 genes was analyzed by real-time polymerase chain reaction. RESULTS: After administration of Vit K2, a dose-dependent decrease in fasting plasma glucose, hemoglobin A1c and homeostatic model assessment method insulin resistance, and a dose-dependent increase in fasting insulin and homeostatic model assessment method ß cell function levels, when compared with diabetes mellitus rats, were detected. There was significant upregulation of OC, Ins 1, Ins 2, or cyclin D2 gene expression in the three treated groups in a dose-dependent manner when compared with the diabetic rats. However, expression of adiponectin and UCP-1 were significantly increased at the highest dose (30 mg/kg daily) only. CONCLUSIONS: Vit K2 administration could improve glycemic status in type 2 diabetic rats by induction of OC gene expression. Osteocalcin could increase ß-cell proliferation, energy expenditure, and adiponectin expression. Different concentrations of Vit K2 were required to affect glucose metabolism and insulin sensitivity.

CYP1A1 gene polymorphisms and smoking status as modifier factors for lung cancer risk.

OBJECTIVE: Lung cancer remains the most prevalent malignancy worldwide. Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes. Several metabolic enzymes are currently under investigation for their possible role in lung cancer susceptibility, including members of the cytochrome P450 (CYP) superfamily. The aim of this work was to identify the correlation between CYP1A1 m1 and m2 polymorphisms and lung cancer risk and figure its interactions with smoking as genetic modifiers in the etiology of lung cancer in the Egyptian population. MATERIALS AND METHODS: One hundred and ten patients with lung cancer and one hundred and ten controls were enrolled in the study. CYP1A1 m1 and m2 polymorphisms were determined using polymerase chain reaction restriction fragment length polymorphism. RESULTS: Subjects carrying TC and CC genotypes of CYP1A1 m1 and AG and GG genotypes of CYP1A1 m2 were significantly more likely to develop lung cancer especially squamous cell carcinoma. The proportion of lung cancer attributable to the interaction of smoking and CYP1A1 m1 and CYP1A1 m2 polymorphisms was 32% and 52% respectively. CONCLUSION: Our results revealed that CYP1A1 m1 and m2 polymorphisms contribute to smoking related lung cancer risk in the Egyptian population.

Synergism of CYP2R1 and CYP27B1 polymorphisms and susceptibility to type 1 diabetes in Egyptian children.

CYP2R1 (25α-hydroxylase) catalyzes vitamin D(3) to 25-hydroxyvitamin D(3), while the CYP27B1 (1α-hydroxylase) catalyzes the 25(OH)D(3) to 1, 25(OH)(2)D(3). 1, 25(OH)(2)D(3) prevents the development of autoimmune diabetes. We aimed to investigate CYP2R1 and CYP27B1 genes polymorphisms and susceptibility to type 1 diabetes in children. One hundred and twenty type 1 diabetic patients and One hundred and twenty controls were genotyped for CYP2R1 (rs10741657) and CYP27B1 (rs10877012) polymorphism. GG genotype of CYP2R1 increased risk to develop type 1 diabetes, and CC genotype of CYP27B1 increased risk to develop type 1 diabetes. Our finding suggested that GG genotype of CYP2R1 polymorphism and/or CC genotype of CYP27B1 polymorphism increased the risk of developing of type 1 diabetes in Egyptian children. In addition there was a synergism between GG genotype of CYP2R1 and CC genotype of CYP27B1 regarding the risk of development of type 1 diabetes.

Adiponectin and some inflammatory and endothelial markers in type-2 diabetes with and without cardiovascular disease.

This study was designed to examine the association between adiponectin and C-reactive protein (CRP), interleukin-6 (IL-6) and endothelin-1, (ET-1) and their possible role in prediction of type-2 diabetes and development of diabetes and macrovascular complications. Forty subjects were studied. They were classified into four equal groups: Control, newly diagnosed type-2 diabetes, diabetics with old myocardial infarction (OMI) and acute myocardial infarction (AMI) groups. They were matched for body mass index (BMI), age, and sex. Adiponectin and IL-6 were determined by ELISA technique, CRP was determined by immunonephlometry and ET-1 was determined by radioimmunoassay. Adiponectin was found to be decreased in newly diagnosed diabetics (6.64 +/- 2.3 microg/ml), OMI (4.7 +/- 1.05 microg/ml) and AMI (4.23 +/- 0.73 microg/ml) when compared to controls (9.81 +/- 2.2 microg/ml), whereas CRP, IL- 6 and ET-1 were significantly elevated in AMI (18.6 +/- 5.3 mg/l, 12.6 +/- 4.2 pg/ml and 36.8 +/- 10.4 fmol/ml, respectively). The changes were marked in AMI group compared to other diabetic groups. Only adiponectin significantly decreased in newly diagnosed type-2 diabetics, but CRP, IL-6 and ET-1 did not significantly altered in newly diagnosed diabetics (4.9 +/- 1.6 mg/l, 6.9 +/- 2.3 pg/ml and 22.1 +/- 8.6 fmol/ml, respectively) compared to control. Adiponectin correlated negatively with CRP, IL-6 and ET-1, BMI and HbA1c, whereas inflammatory and vascular markers correlated positively with each other and with BMI and HbA1c. In conclusions, adiponectin may be implicated in the development of type-2 diabetes and macrovascular complications and can be used as an early predictor of type-2 diabetes. Whereas, none of the inflammatory and vascular markers can predict diabetes, but can be used as markers of acute vascular events and in follow up of these cases. Immunomodulation of adiponectin may help prevention and treatment of type-2 diabetes and its complications.