SENSITIVITY CHANGES OF THE PERFUSED HINDQUARTERS'' VASCULATURE IN RATS WITH ALLOXAN-INDUCED DIABETES MELLITUS

1. Arachidonic acid (AA, 0.125-1.0 mg/kg) injected via the aorta into the autoperfused hindquarters caused dose-dependent increases in perfusion pressure. This effect was reduced after intravenous administration of the thromboxane receptor antagonist AH23848 (5 mg/kg) or indomethacin (5 mg/kg). 2. Responses to AA (0.125-1.0 mg/kg) were reduced markedly in the Krebs-perfused hindquarters when compared with those occurring in the blood-perfused preparation. 3. Doses of guanethidine (1 mg/kg) and pentacynium (1 mg/kg) blocking pressor responses to intravenous administration of the ganglion stimulants McN-A-343 and DMPP, respectively, did not affect responses to AA. 4. Constrictor responses to AA (0.5-1.0 mg/kg) in blood-perfused hindquarters were increased in 14 day alloxan-diabetic rats but those to the thromboxane A2-mimetic U46619 (0.5-8.0 micrograms/kg, i.a.) were reduced when compared with non-diabetic controls. 5. In 14 day alloxan-diabetic rats vasoconstrictor responses to noradrenaline and methoxamine were potentiated but those to 5-hydroxytryptamine were reduced compared with non-diabetic animals. 6. It is concluded that AA causes constriction in the blood-perfused hindquarters by release of a product of cyclo-oxygenase acting on thromboxane A2-receptors. A constituent of blood, perhaps the platelet, appears necessary for this effect. Conversion of AA to the constrictor metabolite is augmented during experimentally induced diabetes.     

四氧嘧啶对大鼠胰岛B细胞损伤机理的实验研究

为探讨四氧嘧啶对大鼠胰岛B细胞的损伤机理,对11只大鼠于尾静脉一次性注射四氧嘧啶50mg/kg体重,以5只为对照。在注药前及注药后两周测其血糖浓度,并对胰腺组织作光、电镜检查。结果发现,注药后血糖明显高于注药前(P<0.01)。光镜下见注药组胰岛数目少,胰岛细胞数锐减,残存者多固缩变性。电镜下见残存B细胞膜模糊不清;核染色质边集成块,核周间隙变宽;线粒体肿胀,嵴断裂空化及出现多数电子致密颗粒;分泌颗粒变型、变小、变少及至形成吞噬性溶酶体;内质网扩张成池并脱颗粒等变化。     

建立四氧嘧啶糖尿病小鼠模型的研究

目的研究四氧嘧啶糖尿病小鼠模型空腹血糖和糖耐量试验的变化规律。方法选择健康小白鼠40只分为正常组、造模1组、造模2组、造模3组,每组10只。其中造模1组、造模2组、造模3组用四氧嘧啶对小鼠进行腹腔注射造模。测定注射前(造模前)空腹血糖和造模后连续多次空腹血糖及糖耐量试验。结果造模组每周测1次空腹血糖,各组均无显著性差异(P均>0.05),造模后2,3,6,9,14,21 d各测1次空腹血糖,仅2,3,6 d造模组各项增高,与正常组比较有显著性差异(P<0.05或<0.01),以后均无显著性升高,个别还低于正常组。第21天进行糖耐量试验,造模组与正常组血糖有显著性差异,空腹血糖虽无显著性,但餐后30 min造模组显著高于正常组,而且餐后2 h血糖不能恢复到空腹或正常组水平。结论四氧嘧啶做小鼠糖尿病造模时,空腹血糖有时不升高或仅有轻度升高,但糖耐量试验出现糖耐量异常,可以判断模型建立成功。     

Age-Related Differences in the Degree of Lipid Peroxidation and State of Antioxidant Protection under the Influence of Alloxan

Alloxan-induced hyperglycemia was accompanied by activation of lipid peroxidation processes with different degree of their completeness depending on the age of experimental animals. Lipid peroxidation in young animals mainly resulted in the formation of end-products, while in adult animals the initial stage of oxidation prevailed. Alloxan inhibited the enzymatic and nonenzymatic systems of antioxidant protection, which impaired adaptation and caused oxidative stress.__________Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 3, pp. 283–286, March, 2005     

Lymphatic system changes in diabetes mellitus: role of insulin and hyperglycemia

BACKGROUND: Diabetic alterations of blood vessels have been well studied, but much less is known about the lymphatic system, which plays an important role in the transport of particles and defensive responses. Accordingly, we investigated lymphatic changes in diabetic rats. METHODS: Ten, 30 or 60 days after alloxan-induced diabetes (40 mg/kg; i.v.), we studied thoracic duct lymph flow and lymphocyte output, thoracic duct lymph transport of radiotracer particles ((99m)Tc-dextran 500), lymph node uptake and scintigraphic visualization of subcutaneously injected radiotracer particles, as well as the effect of insulin administration and food deprivation. RESULTS: Diabetes significantly increased thoracic duct lymph flow and the transport of dextran from the footpad subcutaneous tissue. Abnormal lymphocyte output from the thoracic duct occurred in the first 10 days. Uptake of dextran into regional lymph nodes was decreased in diabetes. Insulin per se, although not normalizing blood sugar levels, appeared to recover thoracic duct lymphocyte output and lymph node uptake of (99m)Tc-dextran 500 without affecting the thoracic duct lymph flow or the amount of radiotracer recovered therein. Normalization of glycemia (by food deprivation) restored the lymph flow to control levels without modifying the lymphocyte output. On the other hand, under insulin-restored normoglycemic conditions, both the thoracic duct lymph flow and the lymphocyte output were normalized. CONCLUSIONS: These findings suggest that variables related to defensive mechanisms, such as lymphocyte recirculation and particles uptake into the lymph nodes can benefit from insulin treatment, whereas glycemic control can benefit transport mechanisms in the lymphatic system, such as lymph flow and lymphatic transport of particles.     

蜜环菌菌索多糖对四氧嘧啶致胰岛细胞损伤的保护作用

目的研究蜜环菌菌索多糖(AMP-1)对四氧嘧啶(AXN)致胰岛细胞损伤的影响。方法培养大鼠胰岛素瘤细胞(INS-1),以AXN损伤细胞,培养液中加入不同浓度的AMP-1(2、10、50、100、500、1000mg.L-1),用MTT法测细胞存活率;使用放免法检测不同浓度AMP-1对INS-1细胞葡萄糖刺激性的胰岛素分泌量的变化;用比色法检测INS-1细胞一氧化氮(NO)、一氧化氮合酶(NOS)、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)等指标的变化。结果AMP-1可减少AXN对INS-1细胞的损伤,AMP-1处理组的INS-1细胞存活率增加;在5.6mmol.L-1、16.7mmol.L-1葡萄糖刺激下,AMP-1(50、100、500、1000mg.L-1)剂量依赖性地促进了INS-1细胞葡萄糖刺激性的胰岛素分泌;AMP-1能使INS-1细胞NOS活性降低,MDA和NO含量减少,同时增强了SOD的活性,增加了GSH的含量。结论一定浓度范围的AMP-1对葡萄糖刺激下INS-1细胞的胰岛素分泌的促进作用,可能与AMP-1能够增加细胞清除自由基能力有关。     

Aortic endothelium of alloxan diabetic rabbits: A quantitative study using scanning electron microscopy

Summary Scanning electron microscope studies of the aorta and other major arteries have been performed in alloxan-induced diabetic rabbits. After 5 weeks, a variety of structural abnormalities of the endothelial lining were detected including a significant increase in the number of argyrophilic cells and an increased number of craters or openings in the endothelial junctional region. Evidence of more extensive micro-damage was present after 5 months duration of diabetes. These zones with structural changes in the endothelial lining of major vessels seem to be areas of high predilection to atherosclerosis in diabetes.     

Effect of genetic background on the capacity for islet cell replication in mice

Summary Proliferation of islet cells may compensate for both an increased peripheral insulin resistance and islet cell destruction but the capacity for regeneration may be genetically determined. For the latter reason, glucose-stimulated islet cell replication was estimated in both inbred C57BL/6J (BL/6) and C57BL/KsJ (BL/Ks) mice. Islets isolated from both strains were exposed to high concentrations of glucose in vitro or in vivo for a prolonged time period. This was achieved either by culturing the islets free-floating in a high glucose concentration medium for 3 days or implanting the islets intrasplenically in insufficient numbers to cure alloxan-diabetic syngeneic recipients. In both strains high glucose concentration culture was found to increase the autoradiographic labelling index of the islets but the replicatory activity decreased with age. The proliferative rate of the islet cells of the BL/6 mice was about twice as high as that of the BL/Ks mice irrespective of age and glucose concentration. Likewise, the labelling index of intrasplenic BL/6 islets implanted into alloxan-diabetic mice was twice as high as that of the islets implanted into alloxan-diabetic BL/Ks mice. The replicatory activity of the latter islets did not differ statistically from that of islets implanted into non-diabetic control BL/Ks mice. No differences in the rates of proinsulin and total protein biosynthetic rates were observed between high glucose concentration-cultured islets of the two mouse strains. The present results indicate that the proliferative response of pancreatic islets to a prolonged glucose stimulation may be genetically determined. This may play a significant role in the development of different diabetic syndromes both in laboratory animals and man.