Chronic vitamin E treatment prevents defective endothelium-dependent relaxation in diabetic rat aorta

Summary We examined the effect in rats of 2 months of streptozotocin-induced diabetes mellitus on relaxation and contraction of aortas in vitro. A further diabetic group was treated from time of diabetes induction with a 1% dietary supplement of vitamin E. Diabetes caused a 26.5% deficit (p<0.001) in maximum endothelium-dependent relaxation to acetylcholine in phenylephrine-precontracted aortas. This was 64.3% attenuated (p<0.01) by vitamin E treatment; maximum relaxation was not significantly altered compared to non-diabetic rats. Vitamin E treatment of non-diabetic rats did not significantly affect acetylcholine-induced relaxation. Diabetes or treatment did not significantly alter acetylcholine sensitivity. Endothelium-independent relaxation response to glyceryl trinitrate was not affected by diabetes or vitamin E treatment, indicating that vascular smooth muscle responses to nitric oxide remained unaltered. There was a 35.4% reduction in the maximum contractile response to phenylephrine with diabetes (p<0.05) which was unaffected by vitamin E treatment. The data suggest that the chronic deficit in nitric oxide-mediated endothelium-dependent relaxation in diabetes depends largely upon excess activity of reactive oxygen species. Treatment with vitamin E to increase free radical scavenging specifically protected vascular endothelium although it had no effect on deficits in vascular smooth muscle contractile responses.Abbreviations NO Nitric oxide - ARI aldose reductase inhibitor - ACH acetylcholine - GTN glyceryl trinitrate - GSH reduced form of glutathione - EC₅₀ effective concentration for 50% of the maximal response     

大黄对实验性糖尿病大鼠肾脏肥大及高滤过作用的影响

肾脏肥大和高滤过是糖尿病肾病出现最早的病理生理特征。本研究利用中药大黄抑制糖尿病的肾脏肥大,试图达到控制其高滤过现象。实验结果表明,大黄能明显地抑制糖尿病肾脏肥大及其组织中蛋白质、DNA含量的增加;大黄治疗组的菊粉清除率明显低于非治疗组;此外,大黄还能使糖尿病血清甘油三酯、胆固醇水平降低。结论:大黄可以通过影响糖尿病肾病肾脏肥大,降低高滤过和纠正血脂代谢紊乱,治疗实验性糖尿病肾病动物模型。     

甜茶素提取物对STZ致高血糖大鼠的降血糖作用研究

目的 :　研究甜茶素提取物对 STZ致高血糖大鼠的降血糖效果及其降糖机制。方法 :　腹腔注射 STZ制备糖尿病大鼠模型 ,取成型的大鼠随机分阳性对照组、甜茶素提取物组和降糖灵组。同时设一正常组。灌胃 3 w后 ,测血糖、果糖胺、胰岛素和 SOD等指标。结果 :　甜茶素提取物能极显著地降低 STZ致高血糖大鼠血糖 ,增强其抗氧化能力 ,同时能刺激胰岛素的分泌。结论 :　甜茶素提取物通过刺激胰岛素的分泌来降低血糖     

Impaired estrogen-induced uterine insulin-like growth factor-I gene expression in the streptozotocin diabetic rat

Summary Circulating somatomedin-C/insulin-like growth factor-I levels are low in the diabetic rat and unresponsive to exogenous growth hormone. However, the nature of this defect in growth hormone action remains unclear and there is little data on insulin-like growth factor-I gene expression in response to other stimuli and in non-hepatic tissues where insulin-like growth factor-I may have important paracrine and/or autocrine actions. We have previously shown that 17-beta estradiol stimulates uterine insulin-like growth factor-I expression in the ovariectomised rat. In this report uterine and hepatic insulin-like growth factor-I gene expression have been examined in the streptozotocin-diabetic rat. Serum insulin-like growth factor-I concentrations were significantly reduced in diabetic rats compared to normal rats (0.72±0.08 vs 1.23±0.05U/ml, p<0.0005) and hepatic insulin-like growth factor-I mRNA abundance was similarly reduced in diabetic rats to 49±5% of that seen in non-diabetic intact rats (p<0.005). In contrast, uterine insulin-like growth factor-I mRNA abundance was not significantly reduced in diabetic rats compared to control rats (76±12%, p = NS). Although both diabetic and non-diabetic rats demonstrated a significant increase in uterine wet weight following a single injection of 17-beta estradiol the increase in uterine insulinlike growth factor-I expression was significantly less marked in diabetic rats. Acute administration of insulin together with estradiol had no significant effect on serum insulin-like growth factor-I concentrations or hepatic insulin-like growth factor-I mRNA abundance; however, the uterine insulin-like growth factor-I response was significantly (p<0.01) augmented. The observations reported here demonstrate that hepatic insulin-like growth factor-I gene expression is markedly reduced in the diabetic rat and that the estradiol-induced uterine insulin-like growth factor-I response is significantly diminished, consistent with the hypothesis that there is a defect in insulin-like growth factor-I gene activation in the diabetic rat.     

The Changes in the Hypothalamo-Pituitary-Gonadal Axis of Streptozotocin-Treated Male Rats Depend from Age at Diabetes Onset

The influence of age at diabetes onset and of capillary microangiopathy on the severity and evolution of hypothalamo-pituitary-gonadal changes was studied morphologically and morphometrically in male rats 4 and 8 months after streptozotocin injection. At each time period we studied 2 groups of rats, one made diabetic before (age 1 month), the other after puberty (age 3 months), and compared them with corresponding controls. The size of hypothalamic axons, numerical density and size of pituitary gonadotrophs, size of testicular tubules, and basement membrane thickness of retinal capillaries were measured. Major differences were found at 8 months. Changes of pituitary glands (i.e. small and numerous gonadotrophs) and testes (i.e. small tubular size) were more important in pre- than in postpubertal diabetic rats. This was a consequence of the aggravating prepubertal diabetes between 4 and 8 months. On the contrary, these changes partially regressed in postpubertal diabetic animals. Pituitary and testicular changes were correlated. Other lesions, such as swollen axonal processes in the hypothalamus, increased thickness of seminiferous epithelium and of capillary basement membranes, though very evident in diabetics, were independent from age at induction. Neither microangiopathy nor glycemia were correlated with any other change which confirmed their secondary role in diabetic neuroendocrine disorders. Thus, two types of diabetic disorders of the hypothalamo-pituitary-gonadal axis could be distinguished: 1) those with irreversible effects on immature yet partially reversible effects on mature structures; and 2) those independent from age at induction.     

Insulin release by glucose anomers in a rat model of non-insulin-dependent diabetes

Summary The effects of the and anomers of D-glucose on insulin release were studied in a rat model of non-insulin-dependent diabetes, which was induced by streptozotocin injection at 2 days of age. Glucose tolerance of the streptozotocin-treated rats at 8–10 weeks of age was mildly diabetic. Insulin release from the isolated perfused pancreas of the diabetic rats in response to 10 mmol/l -D-glucose was markedly impaired, while insulin response to 10 mmol/l -D-glucose in the diabetic pancreas was only slightly reduced as compared to that in the control pancreas.     

Transfected rat islet tumour cells express mouse major histocompatibility complex class I antigens functionally

Summary Rat insulinoma cells clone 5AH-B, were transfected by electroporation with the gene encoding the mouse major histocompatibility complex class I antigen H-2K^b, whereupon stable transfectants were selected and analysed. Data from flow cytometric analyses using three different H-2K^b specific monoclonal antibodies and functional assays using H-2K^b specific alloimmune cytotoxic T cells revealed that the encoded H-2 antigen was expressed in a functional manner. Similar experiments employing the monoclonal antibody OX-18, which recognizes rat major histocompatibility class I molecules, and xenoimmune cytotoxic T cells specific for the endogenously expressed RT1^g antigen showed that functional expression of the RT1^g antigen was maintained. However, a down-regulation of the expression was observed in H-2K^b positive transfectants, whereas normal expression was retained in K^b negative transfectants. The function of the native promoters of both the endogenous and the transfected class I genes was found to be preserved in the transfectants as assessed by the response to stimulation with interferon-. The present study was unable to confirm the reports of RIN specific lysis by T cells from multiple low dose streptozotocin diabetic mice. Even in the presence of the syngeneic restriction element no lysis was observed. We conclude, that rat insulinoma cells clone 5AH-B, are able to integrate a foreign class I antigen gene and express the encoded product functionally. The data also suggest the possibility of creating major histocompatibility antigen positive rat insulinoma cells which are RT1^g negative. Such transfectants will be of great potential value for the dissection of cell mediated B cell destructive processes.     

Protective effect of 3-aminobenzamide,an inhibitor of poly (ADP-ribose) synthetase,against streptozotocin-induced diabetes

Summary The addition of 3-aminobenzamide (a potent inhibitor of poly(ADP-ribose)synthetase) into the incubation medium, prevents streptozotocin-induced inhibition of glucose-stimulated insulin release from isolated islets [control 142±14U·islet^–1·h^–1; streptozotocin (0.5mg/ml) 31±8; 3-aminobenzamide (l.0 mg/ml) 96±11; streptozotocin plus 3-aminobenzamide 122±19]. In vivo, intraperitoneal 3-aminobenzamide 300 mg/kg body weight prevents the appearance of overt diabetes in streptozotocin-treated rats. These protective effects of 3-aminobenzamide are dose-dependent and are similar to those exerted by nicotinamide. Taking into account that poly ADP-ribosylation is involved in the repair of damaged DNA, the protection exerted by 3-aminobenzamide against the diabetogenic effect of streptozotocin strongly supports the view that this acute effect may be a major consequence of the activation of DNA repair mechanisms in islet cells.     

Berberine modulates crucial erectogenic biomolecules and alters histological architecture in penile tissues of diabetic rats

Berberine is an isoquinoline alkaloid, found in several plants. Diabetes induces erectile dysfunction (ED) via reduction in some hormones and enzymes implicated in sexual function. This study aimed to investigate the role of berberine on crucial biomolecules linked to penile function in diabetic rats. Sixty-three (63) adult male rats were used and distributed into nine groups (each = 7). Group I–IV normal rats administered with citrate buffer (pH 4.5), sildenafil citrate (SD, 5.0 mg/kg), 50 and 100 mg/kg of berberine, respectively, via oral gavage. Rats in groups V–IX were diabetic rat with ED treated with buffer, SD, 50 and 100 mg/kg of berberine, and acarbose (25 mg/kg ACA) respectively. The result revealed that histological architecture in penile tissues were altered in diabetic groups treated with berberine, sildenafil citrate and acarbose when compared to the diabetic control group. Treatment with berberine, increased testosterone, luteinizing hormone and follicle-stimulating hormone in diabetic rat with ED. Also, reduced prolactin level and acetylcholinesterase, angiotensin-1 converting enzyme, adenosine deaminase and arginase activities were observed in berberine treated diabetic rat with ED. Molecular docking analysis revealed that berberine had strong binding affinities for these enzymes. Thus, berberine could represent a potential therapeutic agent for diabetes-induced ED.     

Nitric oxide-mediated neurotransmission is attenuated in the anococcygeus muscle from diabetic rats

Summary The effect of STZ-induced diabetes of 8-weeks duration was examined on nitric oxide-mediated neurotransmission in the rat anococcygeus muscle. In the presence of noradrenergic blockade and raised tissue tone, relaxant responses to nerve stimulation (0.5–5 Hz, for 10 s), sodium nitroprusside (5 and 10 nmol/l) and nitric oxide (1 and 3 mol/l) were significantly reduced in anococcygeus muscles from diabetic rats compared to responses from control rats (p <0.05). In contrast, relaxations to papaverine (3 and 10 mol/l were not reduced in tissues from diabetic rats. The nitric oxide synthesis inhibitor NOLA (100 mol/l) abolished relaxant responses to nerve stimulation but had no effect on responses to any of the relaxant agents used. Exposure to NOLA at 10 mol/l reduced stimulation-induced relaxations; this reduction was significantly greater in tissues from the diabetic group than from the control group (p <0.05), probably as a consequence of the smaller relaxant responses in muscles from diabetic rats. Contractile responses to nerve stimulation (1–10 Hz, for 10 s), but not noradrenaline (0.03–30 mol/l), were significantly greater in anococcygeus muscles from diabetic rats than from control rats (p <0.05). NOLA (100 mol/l) significantly enhanced stimulation-induced contractions (p <0.05), however the enhancement was significantly less in tissues from diabetic rats (p <0.05). The results suggest that STZ-induced diabetes impairs smooth muscle reactivity to nitric oxide in the rat anococcygeus muscle.Abbreviations STZ Streptozotocin - NOLA N^G-nitro-l-arginine - NANC nonadrenergic noncholinergic - ANOVA analysis of variance