Abstract
BackgroundIn the present study we tested the hypothesis that progression of streptozotocin (STZ)-induced diabetes (14-days to 28-days) would produce renal and vascular dysfunction that correlate with altered p38- mitogen-activated protein kinase (p38-MAPK) phosphorylation in kidneys and thoracic aorta.MethodsMale Sprague Dawley rats (350–400 g) were randomized into three groups: sham (N = 6), 14-days diabetic (N = 6) and 28-days diabetic rats (N = 6). Diabetes was induced using a single tail vein injection of STZ (60 mg/kg, I.V.) on the first day. Rats were monitored for 28 days and food, water intake and plasma glucose levels were noted. At both 14-days and 28-days post diabetes blood samples were collected and kidney cortex, medulla and aorta were harvested from each rat.ResultsThe diabetic rats lost body weight at both 14-days (-10%) and 28-days (-13%) more significantly as compared to sham (+10%) group. Glucose levels were significantly elevated in the diabetic rats at both 14-days and 28-days post-STZ administration. Renal dysfunction as evidenced by renal hypertrophy, increased plasma creatinine concentration and reduced renal blood flow was observed in 14-days and 28-days diabetes. Vascular dysfunction as evidenced by decreased carotid blood flow was observed in 14-days and 28-days diabetes. We observed an up-regulation of inducible nitric oxide synthase (iNOS), prepro endothelin-1 (preproET-1) and phosphorylated p38-MAPK in thoracic aorta and kidney cortex but not in kidney medulla in 28-days diabetes group.ConclusionThe study provides evidence that diabetes produces vascular and renal dysfunction with a profound effect on signaling mechanisms at later stage of diabetes.
Highlights
Diabetes is a complex and multifarious group of disorders characterized by hyperglycemia that has reached epidemic proportions in the present century
extracellular signal regulated kinase 1 and 2 (ERK1/2) is involved in the growth response of cell while p38-Mitogen-activated protein kinases (MAPKs) and jun N-terminal kinases (JNK) are associated with cellular response to stress [7], inflammation [8] and vasoactive mediators such as endothelin-1 (ET-1) [9]
We speculate a differential regulation of p38-MAPK and ERK1/2 in thoracic aorta and kidneys depending upon the duration and severity of diabetes
Summary
Diabetes is a complex and multifarious group of disorders characterized by hyperglycemia that has reached epidemic proportions in the present century. P38-MAPK activation stimulates inducible nitric oxide synthase (iNOS) expression in serum-deprived RAW 264.7 cells [10]. These observations suggest that signaling mechanisms can regulate various vasoactive molecules and vice-versa. It is still not known if progression of diabetes produces a time dependent activation of p38MAPK in vascular blood vessels and kidneys. In the present study we tested the hypothesis that progression of streptozotocin (STZ)-induced diabetes (14-days to 28-days) would produce renal and vascular dysfunction that correlate with altered p38- mitogen-activated protein kinase (p38-MAPK) phosphorylation in kidneys and thoracic aorta
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