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Streptozotocin-Induced Diabetic Rats (Streptozotocin-Induce + diabetic_rat)
Selected AbstractsAmylin and Bone Metabolism in Streptozotocin-Induced Diabetic RatsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2001Marie-Noėlle Horcajada-Molteni Abstract Amylin (AMY) is a 37 amino acid peptide cosecreted with insulin (INS) by pancreatic ,-cells and absent in type 1 diabetes, a condition frequently associated with osteopenia. AMY binds to calcitonin receptors, lowers plasma calcium concentration, inhibits osteoclast activity, and stimulates osteoblasts. In the present study, we examined the effects of AMY replacement on bone loss in a streptozotocin (STZ)-induced rodent model type 1 diabetes. Of 50 male Wistar rats studied, 40 were made diabetic with intraperitoneal STZ (50 mg/kg; plasma glucose concentrations >11 mM within 5 days). Ten nondiabetic control (CONT) rats received citrate buffer without STZ. Diabetic rats were divided into four groups (n = 10/group) and injected subcutaneously with rat AMY (45 mg/kg), INS (12 U/kg), both (same doses), or saline (STZ; diabetic controls) once per day. After 40 days of treatment and five 24-h periods of urine collection for deoxypyridinoline (DPD), the animals were killed, blood was sampled, and femurs were removed. The left femur was tested for mechanical resistance (three-point bending). The right femur was tested for total, diaphyseal (cortical bone), and metaphyseal (trabecular bone) bone densities using dual-energy X-ray absorptiometry (DXA). Bone was ashed to determine total bone mineral (calcium) content. None of the treatments had any significant effect on femoral length and diameter. Untreated diabetic rats (STZ; 145 ± 7N) had lower bone strength than did nondiabetic CONT (164 ± 38; p < 0.05). Total bone mineral density (BMD; g/cm2) was significantly lower in STZ (0. 2523 ± 0. 0076) than in CONT (0.2826 ± 0.0055), as were metaphyseal and diaphyseal densities. Diabetic rats treated with AMY, INS, or both had bone strengths and bone densities that were indistinguishable from those in nondiabetic CONT. Changes in bone mineral content paralleled those for total BMD (T-BMD). Plasma osteocalcin (OC) concentration, a marker for osteoblastic activity, was markedly lower in untreated diabetic rats (7. 6 ± 0. 9 ng/ml); p < 0. 05) than in nondiabetic CONT (29. 8 ± 1. 7; p < 0. 05) or than in AMY (20. 1 ± 0. 7; p < 0. 05). Urinary DPD excretion, a marker for bone resorption, was similar in untreated and AMY-treated diabetic rats (35.0 ± 3.1 vs. 35.1 ± 4.4 nmol/mmol creatinine), intermediate in rats treated with INS (49.9 ± 2.7), and normalized in diabetic rats treated with both agents (58.8 ± 8.9 vs. 63.2 ± 4.5 in CONT). Thus, in our STZ rat model of diabetic osteopenia, addition of AMY improved bone indices apparently by both inhibiting resorption and stimulating bone formation. [source] Inhibition of Leukocyte Adherence Enables Venular Control of Capillary Perfusion in Streptozotocin-Induced Diabetic RatsMICROCIRCULATION, Issue 8 2004KAVITHA NELLORE ABSTRACT Objective: Vasoactive molecules can diffuse from venules to dilate closely paired arterioles and enhance capillary perfusion. Venular control of capillary flow has been found to be dependent on nitric oxide (NO), which might be scavenged rapidly in diabetic microvasculature due to the presence of activated leukocytes. This study attempts to improve venular control of capillary flow using fucoidan, which inhibits venular leukocyte adhesion. Methods: Microvascular red blood cell velocity was measured in the mesentery of streptozotocin-induced diabetic rats, with and without fucoidan treatment, and in normal rats. Arteriolar pathways leading to branching capillaries were videotaped to measure the percent of the surrounding area occupied by a venule (% pairing). Microvascular wall NO was measured using fluorescent diaminofluorescein-2-diacetate in diabetic rats, with and without fucoidan treatment. Results: In normal rats, close pairing of venules to arterioles resulted in faster capillary flow. However, after 4,5 weeks of diabetes, the correlation between capillary velocity and % pairing was no longer significant. Capillary velocity and % pairing decreased , 50% in comparison to normal rats. Treatment of diabetic rats with fucoidan restored venular control of capillary flow and increased NO levels. Conclusion: Leukocyte-derived mediators that scavenge NO may lead to inadequate venular control of capillary flow in diabetes. [source] Role of Increased Penile Expression of Transforming Growth Factor-,1 and Activation of the Smad Signaling Pathway in Erectile Dysfunction in Streptozotocin-Induced Diabetic RatsTHE JOURNAL OF SEXUAL MEDICINE, Issue 10 2008Lu Wei Zhang MD ABSTRACT Introduction., It has been suggested that transforming growth factor-,1 (TGF-,1) plays an important role in the pathogenesis of diabetes-induced erectile dysfunction. Aim., To investigate the expression and activity of Smad transcriptional factors, the key molecules for the initiation of TGF-,-mediated fibrosis, in the penis of streptozotocin (STZ)-induced diabetic rats. Methods., Fifty-two 8-week-old Sprague,Dawley rats were used and divided into control and diabetic groups. Diabetes was induced by an intravenous injection of STZ. Main Outcome Measures., Eight weeks later, erectile function was measured by electrical stimulation of the cavernous nerve (N = 12 per group). The penis was harvested and stained with Masson trichrome or antibody to TGF-,1, phospho-Smad2 (P-Smad2), smooth muscle ,-actin, and factor VIII (N = 12 per group). Penis specimens from a separate group of animals were used for TGF-,1 enzyme-linked immunosorbent assay (ELISA), P-Smad2/Smad2, phospho-Smad3 (P-Smad3)/Smad3, fibronectin, collagen I, and collagen IV western blot, or hydroxyproline determination. Results., Erectile function was significantly reduced in diabetic rats compared with that in controls. The expression of TGF-,1, P-Smad2, and P-Smad3 protein evaluated by ELISA or western blot was higher in diabetic rats than in controls. Compared with that in control rats, P-Smad2 expression was higher mainly in smooth muscle cells and fibroblasts of diabetic rats, whereas no significant differences were noted in endothelial cells or in the dorsal nerve bundle. Cavernous smooth muscle and endothelial cell contents were lower in diabetic rats than in controls. Cavernous fibronectin, collagen IV, and hydroxyproline content was significantly higher in diabetic rats than in controls. Conclusion., Upregulation of TGF-,1 and activation of the Smad signaling pathway in the penis of diabetic rats might play important roles in diabetes-induced structural changes and deterioration of erectile function. Zhang LW, Piao S, Choi MJ, Shin H-Y, Jin H-R, Kim WJ, Song SU, Han J-Y, Park SH, Mamura M, Kim S-J, Ryu J-K, and Suh J-K. Role of increased penile expression of transforming growth factor-,1 and activation of the Smad signaling pathway in erectile dysfunction in streptozotocin-induced diabetic rats. J Sex Med 2008;5:2318,2329. [source] The Breakdown of Preformed Advanced Glycation End Products Reverses Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats: Preventive Versus Curative TreatmentTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2006Mustafa F. Usta MD ABSTRACT Objectives., Accumulation of advanced glycation end products (AGEs) has been linked to many of the complications of diabetes mellitus, including erectile dysfunction (ED). Furthermore, it has been demonstrated that inhibitors of AGE formation, such as aminoguanidine, can prevent ED in diabetic animals. However, it is unknown whether late administration of a putative cross-link breaker, ALT-711, can reverse diabetic ED. We therefore compared ALT-711 and aminoguanidine in their ability to reverse ED in diabetic rats. Materials and Methods., Male Sprague,Dawley rats were randomly divided into four groups: (i) age-matched controls; (ii) streptozotocin (STZ)-induced diabetic rats (60 mg/kg; intraperitoneal injection); (iii) STZ diabetic rats treated with ALT-711 (3 mg/kg/day, intraperitoneal injection); and (iv) STZ diabetic rats treated with aminoguanidine (1 gm/L in drinking water) during the final 6 weeks of 12 weeks of induced diabetes. At the end of 12 weeks, erectile response to cavernous nerve stimulation (CNS) was determined. Neuronal nitric oxide synthase (nNOS) contents were measured in all penises, and AGE levels were determined both in penile tissues and in serum samples. Results., Erectile responses to CNS and penile nNOS protein content were significantly reduced, while AGE levels were elevated in the penises and serum of untreated diabetic animals. Treatment with ALT-711, but not with aminoguanidine, reversed ED and nNOS depletion and reduced serum and penile tissue AGE levels. Conclusions., These results suggest that cross-link breakers, such as ALT-711, are the optimal therapeutic approach, compared with treatment with inhibitors of AGE formation, in the reversal of diabetes-related ED. Usta MF, Kendirci M, Gur S, Foxwell NA, Bivalacqua TJ, Cellek S, and Hellstrom WJG. The breakdown of preformed advanced glycation end products reverses erectile dysfunction in streptozotocin-induced diabetic rats: Preventive versus curative treatment. J Sex Med 2006;3:242,252. [source] Effects Of The New Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor Fluvastatin On Anti-Oxidant Enzyme Activities And Renal Function In Streptozotocin-Induced Diabetic RatsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2000Atsushi Kurusu SUMMARY 1. The effects of 11 week treatments with the new hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin on renal intrinsic anti-oxidant enzyme (AOE) activities and renal function were evaluated in streptozotocin (STZ)-induced diabetic rats. 2. Renal intrinsic AOE activities, creatinine clearance and urinary albumin excretion were examined in STZ-induced diabetic rats. The levels of total cholesterol (TC), triglyceride (TG) and phospholipid (PL) were also examined. 3. In general, renal AOE activities and function were lower in diabetic rats than in non-diabetic Sprague-Dawley rats. 4. Decreases in TC, TG and PL levels and urinary albumin excretion by the HMG-CoA reductase inhibitor fluvastatin improved renal function and produced a non-uniform alteration in renal AOE; only glutathione peroxidase (GSH-Px) activity increased significantly with fluvastatin treatment. 5. It appears that the improvement in renal function and albuminuria may be related to increases in GSH-Px activity, but there was no correlation between changes in renal function and changes in the activity of Mn-superoxide dismutase or catalase. [source] | ||||||||||