ABSTRACT
11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD-1) activity and mRNA levels are increased in visceral and subcutaneous adipose tissues of metabolic syndrome subjects. We analyzed 11ß-HSD-1 expression in human epicardial adipose (EA) and ascending aorta (AA) tissues of metabolic syndrome patients and examined their contribution to the development of coronary atherosclerosis. The 11ß-HSD-1 expression was evaluated by qRT-PCR in EA and AA tissues of 20 metabolic syndrome patients with coronary artery disease (metabolic syndrome group) and 10 non-metabolic syndrome patients without coronary artery disease (controls). 11ß-HSD-1 expression was increased in EA and AA tissues of the metabolic syndrome group (4.1- and 5.5-fold, respectively). A significant positive correlation was found between 11ß-HSD-1 expression in EA tissue and waist hip ratio and 11ß-HSD-1 expression in AA tissue and body mass index, while a negative correlation was found between 11ß-HSD-1 expression in EA tissue and HDL. Expression of CD68, a macrophage marker, was significantly increased in both tissues of the metabolic syndrome group; it was 2-fold higher in AA tissue compared to EA tissue in the metabolic syndrome group. Our findings of increased expression of 11ß-HSD-1 and CD68 in AA tissue of the metabolic syndrome group lead us to suggest that they contribute to coronary atherosclerosis in metabolic syndrome. This positive correlation between obesity markers and 11ß-HSD-1 in AA and EA tissues strengthens the evidence that 11ß-HSD-1 has a role in metabolic syndrome. To the best of our knowledge, this is the first report showing 11ß-HSD-1 and CD68 expression in AA tissue of metabolic syndrome patients. We suggest that there is tissue-specific expression of 11ß-HSD-1 in metabolic syndrome and associated cardiovascular disorders.
Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1/genetics , Aorta/enzymology , Aorta/pathology , Coronary Artery Disease/enzymology , Coronary Artery Disease/genetics , Gene Expression Regulation, Enzymologic , Metabolic Syndrome/enzymology , 11-beta-Hydroxysteroid Dehydrogenase Type 1/metabolism , Anthropometry , Case-Control Studies , Coronary Artery Disease/complications , Female , Humans , Male , Metabolic Syndrome/complications , Metabolic Syndrome/genetics , Middle Aged , Pericardium/enzymology , Pericardium/pathologyABSTRACT
The effects of calcium channel blockers (CCB)-verapamil, nifedipine, diltiazem on metabolic control in streptozotocin-induced long-term diabetes in rats were investigated. Diabetes mellitus was induced by single intravenous injection of streptozotocin (65 mg/kg body wt.). The animals were divided into five groups: a healthy control group, a diabetic group and three diabetic groups treated with one of the calcium channel blockers (verapamil, 25 mg/kg/day, nifedipine, 20 mg/kg/day, and diltiazem, 30 mg/kg/day, respectively). Body weight, glycemia, glycated hemoglobin and total serum protein levels of these animals were measured at the beginning and at the end (after 13 weeks) of the experiment. It was observed that diabetic animals who were not treated with CCB had lost weight at the end of the experiment (P < 0.01). The blood glucose and glycated hemoglobin levels were increased in the diabetic group in comparison to the healthy control group (P < 0.001). However, the calcium channel blockers seem to have beneficial effects on body weight, glycated hemoglobin and blood glucose levels.
Subject(s)
Blood Glucose/metabolism , Calcium Channel Blockers/pharmacology , Diabetes Mellitus, Experimental/blood , Diltiazem/pharmacology , Nifedipine/pharmacology , Verapamil/pharmacology , Animals , Blood Glucose/drug effects , Blood Proteins/drug effects , Blood Proteins/metabolism , Body Weight/drug effects , Diabetes Mellitus, Experimental/physiopathology , Glycated Hemoglobin/drug effects , Glycated Hemoglobin/metabolism , Male , Rats , Rats, Wistar , Reference ValuesABSTRACT
The pathogenesis of spontaneous remission in Type 1 diabetes is poorly understood. To clarify this particular phase of the disease, experimental autoimmune diabetes induced by multiple low doses of streptozotocin (M-STZ) in mice was used as an experimental tool. Balb/C mice received five doses of 40 mg of STZ (diabetic group) or citrate buffer (controls) during five consecutive days. Heparinized blood samples were collected from these animals' orbital sinus in the morning following 8-12 h of fasting, before and at the 7th, 14th and 21st day after the first injection of STZ. Plasma glucose, insulin and islet cell antibodies (ICA) were determined. The animals were killed at the 21st day; their pancreata and abdominal lymph nodes were removed for morphometric and immunocytochemical examinations. Induction of hyperglycaemia occurred on the first or second day after STZ injection. Sustained hyperglycaemia, hypo-insulinaemia and islet cell antibody positivity were observed in diabetic animals. Morphometric analysis of the pancreata reveals a spectrum of mild to extensive mononuclear cell infiltration and varying degrees of beta cell destruction. In the same diabetic pancreas, morphometric analysis of islets' sections reveals a normal appearance in 42% and varying degrees of insulitis in 58%; ductulitis in 20% and islets' necrosis in 48%, indicating that many immune assaults take place simultaneously and subsequently. Furthermore, plasmocytic transformation in diabetic lymph nodes was observed, disclosing the appearance of ICA's positivity. Concerning immunocytochemical findings, alpha, beta and delta cells were normal in appearance in controls; while beta cells of inflamed islets were filled with insulin and alpha cells appeared to be hyperplastic in the diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)
