ABSTRACT
BACKGROUND: Vascular endothelial growth factor (VEGF) is associated with the development of diabetic complications. However, it is unknown whether systemic VEGF treatment has any effects on the pancreatic islets in an animal model of type 2 diabetes mellitus. METHODS: Anti-VEGF peptide (synthetic ATWLPPR, VEGF receptor type 2 antagonist) was injected into db/db mice for 12 weeks. We analyzed pancreatic islet morphology and quantified beta-cell mass. Endothelial cell proliferation and the severity of islet fibrosis were also measured. VEGF expression in isolated islets was determined using Western blot analysis. RESULTS: When anti-VEGF was administered, db/db mice exhibited more severe hyperglycemia and associated delayed weight gain than non-treated db/db mice. Pancreas weight and pancreatic beta-cell mass were also significantly decreased in the anti-VEGF-treated group. VEGF and VEGF receptor proteins (types 1 and 2) were expressed in the pancreatic islets, and their expression was significantly increased in the db/db group compared with the db/dm group. However, the elevated VEGF expression was significantly reduced by anti-VEGF treatment compared with the db/db group. The anti-VEGF-treated group had more prominent islet fibrosis and islet destruction than db/db mice. Intra-islet endothelial cell proliferation was also remarkably reduced by the anti-VEGF peptide. CONCLUSION: Inhibition of VEGF action by the VEGF receptor 2 antagonist not only suppressed the proliferation of intra-islet endothelial cells but also accelerated pancreatic islet destruction and aggravated hyperglycemia in a type 2 diabetes mouse model. Therefore, the potential effects of anti-VEGF treatment on pancreatic beta cell damage should be considered.
Subject(s)
Animals , Mice , Blotting, Western , Diabetes Complications , Diabetes Mellitus, Type 2 , Endothelial Cells , Endothelial Growth Factors , Fibrosis , Hyperglycemia , Insulin-Secreting Cells , Islets of Langerhans , Models, Animal , Pancreas , Proteins , Receptors, Vascular Endothelial Growth Factor , Vascular Endothelial Growth Factor A , Weight GainABSTRACT
BACKGROUND: Recent studies suggest that serum Cystatin C is both a sensitive marker for renal dysfunction and a predictive marker for cardiovascular diseases. We aimed to evaluate the association between Cystatin C and various biomarkers and to find out its utility in estimating risk for cardiovascular diseases in type 2 diabetic patients. METHODS: From June 2006 to March 2008, anthropometric measurements and biochemical studies including biomarkers for risk factors of cardiovascular diseases were done in 520 type 2 diabetic patients. A 10-year risk for coronary heart diseases and stroke was estimated using Framingham risk score and UKPDS risk engine. RESULTS: The independent variables showing statistically significant associations with Cystatin C were age (beta = 0.009, P < 0.0001), hemoglobin (beta = -0.038, P = 0.0006), serum creatinine (beta = 0.719, beta < 0.0001), uric acid (beta = 0.048, P = 0.0004), log hsCRP (beta = 0.035, P = 0.0021) and homocysteine (beta = 0.005, P = 0.0228). The levels of microalbuminuria, carotid intima-media thickness, fibrinogen and lipoprotein (a) also correlated with Cystatin C, although the significance was lost after multivariate adjustment. Calculated risk for coronary heart diseases increased in proportion to Cystatin C quartiles: 3.3 +/- 0.4, 6.2 +/- 0.6, 7.6 +/- 0.7, 8.4 +/- 0.7% from Framingham risk score (P < 0.0001); 13.1 +/- 0.9, 21.2 +/- 1.6, 26.1 +/- 1.7, 35.4 +/- 2.0% from UKPDS risk engine (P < 0.0001) (means +/- SE). CONCLUSIONS: Cystatin C is significantly correlated with various emerging biomarkers for cardiovascular diseases. It was also in accordance with the calculated risk for cardiovascular diseases. These findings verify Cystatin C as a valuable and useful marker for predicting future cardiovascular diseases in type 2 diabetic patients.
Subject(s)
Humans , Biomarkers , Cardiovascular Diseases , Carotid Intima-Media Thickness , Coronary Disease , Creatinine , Cystatin C , Fibrinogen , Hemoglobins , Homocysteine , Lipoprotein(a) , Risk Factors , Stroke , Uric AcidABSTRACT
We report here on a case of a 22-year-old girl with a suprasellar mass that was originally diagnosed as lymphocytic hypophysitis, but it eventually turned out to be a germinoma. She initially underwent partial tumor removal and the tissue diagnosis was suggestive of lymphocytic hypophysitis. 46 months later, she presented with a lateral visual field defect and decreased visual acuity of her right eye. The serum and cerebrospinal beta-hCG and alpha-fetoprotein levels were measured. The beta-hCG level was elevated in both, whereas the alpha-fetoprotein level was detectable in neither. The serum anti-pituitary antibody-1 level was negative. She was reoperated and the permanent section biopsies were compatible with pure germinoma. There was no evidence of meningeal metastasis on her whole spine MRI. She was treated with chemotherapy.