糖糠平降糖机制研究

目的:研究糖糠平的降糖机制。方法:观察糖糠平(YG-1)对四氧嘧啶糖尿病模型小鼠血糖、甘油三酯降低的影响;对蔗糖负荷四氧嘧啶糖尿病模型小鼠血糖升高的影响;对ip葡萄糖负荷大鼠胰岛素释放的影响。结果:YG-1对四氧嘧啶糖尿病小鼠血糖、甘油三酯有显著降低作用(P<0.05);对蔗糖负荷四氧嘧啶糖尿病小鼠血糖升高有显著抑制作用(P<0.05);对ip葡萄糖负荷大鼠胰岛素释放有显著增加作用(P<0.05)。结论:YG-1的降糖机制可能为类胰岛素作用,以及改变了靶细胞对内原性胰岛素敏感性的增强。     

Effects of canatoxin on the Ca(2+)-ATPase of sarcoplasmic reticulum membranes.

Canatoxin, a toxic protein isolated from the seeds of Canavalia ensiformis, was studied for its effects on the sarcoplasmic reticulum vesicles obtained from rabbit skeletal muscle. Canatoxin inhibited Ca2+ accumulation catalysed by the Ca(2+)-ATPase, without affecting the hydrolytic activity of this enzyme or membrane permeability to Ca2+. The effects of canatoxin were dose dependent, but not time dependent. It is concluded that canatoxin interacts with the Ca2+ pump and uncouples Ca2+ uptake from Ca(2+)-dependent ATP hydrolysis.     

Effect of ecdysterone on hyperglycemia in experimental animals

Ecdysterone, one of the insect-metamorphosing steroids isolated from plants (Amaranthaceae: Achyranthes fauriei), has been recognized to have a suppressive effect on hyperglycemia induced by several hyperglycemic agents. While the administration of ecdysterone did not alter the blood glucose level of normal animals, pretreatment with ecdysterone prior to hyperglycemic agents suppressed the hyperglycemia induced both by glucagon and by anti-insulin serum at only low levels as well. The effect of ecdysterone was also demonstrated using alloxan-diabetic animals. After the administration of ecdysterone to alloxan-diabetic mice, the blood glucose level was reduced to about one-half of the value observed before the administration of ecdysterone. The incorporation of [¹⁴C]glucose into protein of normal mouse liver and into glycogen of normal and mildly diabetic mouse liver was stimulated by treatment with ecdysterone.     

木姜叶柯总黄酮对大小鼠血糖和糖耐量的影响

目的 探讨木姜叶柯总黄酮对大小鼠血糖和糖耐量的影响.方法 采用遗传性高血糖小鼠、四氧嘧啶诱发高血糖小鼠模型、链脲菌素诱发大鼠高血糖模型,观察木姜叶柯总黄酮对大小鼠血糖和糖耐量的影响.结果 与模型组比较,木姜叶柯总黄酮低、中、高剂量(50、100、200 mg/kg)给药,明显降低遗传性高血糖小鼠的空腹血糖(P＜0.05);显著降低四氧嘧啶诱发高血糖小鼠的空腹血糖(P＜0.05),同时能显著改善其糖耐量(P＜0.05).木姜叶柯总黄酮低、中、高剂量(30、60、120 mg/kg)给药明显降低链脲菌素诱发高血糖大鼠的空腹血糖(P＜0.05)并能显著改善高血糖大鼠糖耐量(P＜0.05).结论 木姜叶柯总黄酮能显著改善高血糖大小鼠的血糖水平和糖耐量,提示其可用于糖尿病的治疗.     

丹皮多糖-2b降血糖作用的实验研究

目的：研究丹皮多糖－2b（CMP－2b)降血糖作用及作用机制。方法：用小鼠和大鼠建立葡萄糖性高血糖及四氧嘧啶性糖尿病模型，氢化可的松琥珀酸纳（HCSS)诱导胰岛素抵抗，观察丹皮多糖－2b对正常和高血糖模型动物的影响，并测定糖尿病动物SOD、Insulin、GHb、ApoA1等水平。结果：CMP－2b可降低葡萄糖和四氧嘧啶诱发的鼠高血糖，并能升高糖尿病小鼠SOD和大鼠ApoA1水平，降低GHb水平，改善小鼠胰岛素抵抗。结论：CMP－2b可有效地控制实验性高血糖，其降糖机理可能与改善机体对胰岛素的敏感性，促进外周组织对葡萄糖的利用有关。     

Dopamine agonist-induced hyperglycemia in rats: structure-activity relationships and mechanisms of action

The concentration of blood glucose was measured in rats after administration of a number of drugs characterized as dopamine agonists. Compounds that cause release of dopamine, or agents that block the reuptake of dopamine, did not elevate blood glucose. Some direct dopamine receptor stimulants (lergotrile, bromocriptine, apomorphine) caused hyperglycemia, but other agonists (e.g. pergolide) did not. Further experiments with lergotrile, the most active hyperglycemic dopamine agonist, revealed that the blood glucose increase was accompanied by a marked elevation in liver glycogen, indicating a gluconeogenic effect of the compound. This hypothesis was supported by using inhibitors of gluconeogenesis (L-tryptophan or 3-mercaptopicolinic acid) to block lergotrile's hyperglycemic action. Structure-activity relationships among close analogues of lergotrile suggest that the cyano moiety in the lergotrile molecule may be of importance in the hyperglycemic action of lergotrile. These results indicate that central dopamine stimulation per se does not cause hyperglycemia in rats.     

Different neuroprotective responses of Ginkgolide B and bilobalide, the two Ginkgo components, in ischemic rats with hyperglycemia

Ginkgo biloba extracts show neuroprotective effects during cerebral ischemia, but with various components, the mechanisms of action remain unclear. In this study, we tested the effects of Ginkgolide B (GB) and bilobalide (BB) on normoglycemic and hyperglycemic rats subjected to transient cerebral ischemia. Rats were administered p.o. with different Ginkgo components GB (6 mg/kg) or BB (6 mg/kg) once daily for 7 days. Hyperglycemia was made by jugular vein infusion of glucose and transient middle cerebral artery occlusion/reperfusion was induced by a suture insertion technique. Results showed that both GB and BB exerted neuroprotection under normoglycemia, as determined by infarct volume and neurological deficit scores. Yet, BB showed less protective effects during hyperglycemic cerebral ischemia. Cerebral blood flow (CBF) was evaluated during occlusion and the first hour of reperfusion. BB but not GB caused acute increase in CBF after reperfusion, especially in hyperglycemia. Reactive oxygen species and malondialdehyde levels were reduced by GB in both models but BB were not effective in reactive oxygen species or malondialdehyde control in hyperglycemia ischemic rats. These results suggested that CBF plays crucial roles during early stage of reperfusion in the presence of hyperglycemia. Administration of compound that improves CBF may have little effect in hyperglycemic stroke.     

灵芝多糖调节血糖血脂作用的实验研究

目的:研究灵芝多糖对四氧嘧啶致高血糖大鼠血糖、血脂水平及四氧嘧啶致高血糖小鼠、去甲肾上腺素致高血糖小鼠及正常小鼠血糖水平的影响.方法:制备四氧嘧啶致高血糖大鼠模型,给药4周后取血测定血糖及血脂水平;制备四氧嘧啶致糖尿病小鼠模型及去甲肾上腺素致高血搪小鼠模型,给药2周后取血测定血搪水平.结果:灵芝多搪能明显降低四氧嘧啶所致搪尿病大鼠的血糖和血脂水平,其中高剂量组与模型对照组相比均有显著意义(P<0.05),并能明显降低四氧嘧啶所致糖尿病小鼠及去甲肾上腺素所致高血糖小鼠的血糖水平,其中高剂量组与模型对照组相比均有显著意义(P<0.05),而对正常小鼠血糖水平影响较小、低、中、高剂量组与正常对照组相比均无显著意义(P>0.05).结论:灵芝多糖对四氧嘧啶致高血糖大鼠有明显的降血搪、血脂作用,对四氧嘧啶致高血糖小鼠及去甲肾上腺素致高血糖小鼠具有明显降血搪作用,而对正常小鼠血糖水平影响较小.     

Effects of acute and subacute cadmium administration on carbohydrate metabolism in mice

The administration of single doses of cadmium acetate (2.0–6.0 mg/kg, ip) produces hyperglycemia and glucose intolerance in intact mice. Adrenalectomy prevents the hyperglycemic effect but not the glucose intolerance. Glucose intolerance is associated with a decreased pancreatic secretory activity as evidenced by decreased insulinogenic indices in Cd-treated mice. The administration of 4.0 mg/kg of Cd daily for 14 days produces tolerance to Cd-induced hyperglycemia. The subacute treatment did not produce changes in resting blood glucose levels, nor did it produce a decrease in glucose tolerance. A significant reduction in circulating serum insulin was detected after subacute Cd administration. It is suspected that a Cd-induced decrease in renal threshold to glucose masks the effect of lowered serum insulin concentrations.     

乌拉坦诱导的高血糖反应(英文)

目的:观察麻醉剂量的乌拉坦对空腹大鼠、葡萄糖负荷大鼠,肾上腺素或四氧嘧啶诱发高血糖大鼠血糖水平的影响,并探讨其对外源性胰岛素降血糖作用的影响。方法:葡萄糖氧化酶法测定血糖含量。结果:麻醉剂量1.5g·kg~(-1)乌拉坦(sc,ip各半)显著升高空腹大鼠和葡萄糖负荷大鼠的血糖水平,但对肾上腺素(胰岛功能正常)或四氧嘧啶(胰岛功能受损)诱发的高血糖大鼠的血糖水平无明显影响。在四氧嘧啶诱发的高血糖大鼠,乌拉坦显著对抗外源性胰岛素的降血糖作用。结论:乌拉坦升高血糖的作用除与已知的释放肾上腺素有关外,抑制胰岛素的降血糖作用也是其升高血糖的机制之一。     

Effects of acute and chronic hyperglycemia on morphine-induced inhibition of gastrointestinal transit in mice

Using the charcoal meal test, the effects of morphine (3, 5 and 7 mg/kg) on gastrointestinal transit was assessed in normoglycemic as well as in acute and chronic hyperglycemic mice. Acute hyperglycemia was induced by intraperitoneal injection of glucose (5.04 g/kg), while chronic hyperglycemia was induced by streptozotocin injection (200 mg/kg i.p., 7-8 days before). Acute hyperglycemia augmented the inhibitory effect of morphine on gut transit, however, chronic hyperglycemia failed to modify the effects of morphine. The results indicate that hyperglycemia per se may not be the primary mechanism for the altered sensitivity to morphine in experimental models of diabetes.     

人参糖肽的降血糖作用(英文)

目的:研究人参糖肽降血糖作用。方法:观察人参糖肽对正常小鼠或家兔以及由四氧嘧啶和链尿菌素引起高血糖大鼠或小鼠的降血糖作用。血糖和肝糖元含量分别用显色剂邻甲苯胺和碘试剂呈色后,用分光光度计测定。结果:给正常小鼠ip或sc人参糖肽(50,100和200mg/kg)或按30和60mg/g剂量给正常家兔im人参糖肽,能明显降低正常动物的血糖和肝糖元,并且有剂量依赖关系;人参糖肽降血糖作用可持续16h;其次,人参糖肽对实验性高血糖动物也有明显的降血糖活性。结论:注射人参糖肽无论对正常动物还是高血糖动物都有明显的降低血糖和肝糖元作用。     

广西藤茶中杨梅树皮素降血糖的实验研究

目的 观察杨梅树皮素(MYR)对多种动物模型的降血糖作用。方法 采用四氧嘧啶所致糖尿病模型、肾上腺素和葡萄糖引起的高血糖小鼠模型，以及正常小鼠，在口服给药后，测定各模型小鼠的血糖水平。结果 MYR对四氧嘧啶所致糖尿病小鼠有较好的治疗作用，对肾上腺素、葡萄糖引起的高血糖小鼠也有明显的降血糖作用，但对正常小鼠血糖无明显影响。结论 MYR对多种动物模型具有较好的降血糖作用。     

Metabolic changes induced by urethane-anesthesia in rats

1. Fasting hyperglycemia was observed in urethane-anesthetized rats. No significant changes had been observed in fed animals. The effect is dose-dependent, being ineffective doses lesser than 1.4 g/kg of body weight. 2. Urethane originates a rise in glycemia during the first 10 min of anesthesia followed by control values at 30 min, and a latter hyperglycemic phase for more than 60 min that remain at 2 hr. 3. The negative correlationship between plasma glucose, lactate and amino acid levels suggest that gluconeogenesis may be the main responsibility of the observed hyperglycemia during the first phase, but it is possible that during the second phase a decrease in the consumption of glucose may take place as a consequence of the competitive effects of ketone bodies increased during the first 30 min of anesthesia. 4. We postulate that the mechanism of the hyperglycemic response to urethane is a sympathetic response with release of catecholamines both in the liver and in the adrenal gland which enhances gluconeogenesis and lipolysis.     

乌拉坦对大鼠胰岛素水平的影响(英文)

目的　观察麻醉剂量的乌拉坦对空腹大鼠、葡萄糖负荷大鼠和肾上腺素诱发高血糖大鼠血浆胰岛素水平的影响。方法　采用放射免疫测定法测定血浆胰岛素活性。结果　麻醉剂量的乌拉坦 (1 .5g·kg-1 ,sc ,ip各半 )给药后 2 0min显著升高空腹大鼠及葡萄糖负荷大鼠血浆胰岛素水平 ,给药后 50min血浆胰岛素水平分别从 (1 1± 4)及 (1 1± 4)mU·L-1 升至 (2 5±1 1 )及 (47± 6)mU·L-1 ;相同剂量的乌拉坦给药后 1 4 0min使肾上腺素诱发的高血糖大鼠血浆胰岛素水平从 (1 0± 3)升至 (51± 1 8)mU·L-1 。与血浆胰岛素水平的变化相比 ,乌拉坦给药后 50min显著升高空腹大鼠和葡萄糖负荷大鼠的血糖水平 ,但对肾上腺素诱发的高血糖大鼠的血糖水平无明显影响。结论　乌拉坦显著升高空腹大鼠、葡萄糖负荷大鼠及肾上腺素诱发的高血糖大鼠血浆胰岛素水平。乌拉坦促进胰岛素分泌的机制包括高血糖依赖性促分泌和非血糖依赖性促分泌两种     

Platelet release reaction and aggregation induced by canatoxin, a convulsant protein: evidence for the involvement of the platelet lipoxygenase pathway.

Canatoxin is a toxic protein isolated from Canavalia ensiformis seeds. It induces death preceded by convulsions of spinal cord origin and also produces in vitro aggregation of platelets in rabbit, human and guinea-pig plasma. The aggregating effect is dose-dependent at nanomolar concentrations. Rabbit platelets pretreated with canatoxin became refractory to a second exposure to this protein or to collagen, but were still responsive to ADP, Paf-acether or arachidonic acid. [14C]-5-hydroxytryptamine was released from pre-labelled platelets on stimulation with canatoxin. Washed rabbit platelets, but not thrombin-degranulated ones, aggregated on stimulation with canatoxin provided that fibrinogen was added before the toxin. Canatoxin's pro-aggregating activity was inhibited by mepacrine, EDTA, caffeine, prostacyclin, adenosine monophosphate and also by the ADP scavenger system, creatine phosphokinase/creatine phosphate. Furthermore, 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW 755C), eicosatetraynoic acid (ETYA) and nordihydroguaiaretic acid (NDGA) were potent inhibitors of canatoxin-induced aggregation. In contrast, no inhibition was seen with indomethacin. The data indicate that canatoxin is mainly a release-reaction-promoting agent, being devoid of any direct aggregating activity. Thus the aggregation is totally dependent on the release of ADP. Furthermore, canatoxin-induced platelet activation is probably dependent on platelet phospholipase A2 and lipoxygenase activity but is not dependent on cyclo-oxygenase products or the release of Paf-acether.     

Central Nervous Effects of the Convulsant Protein Canatoxin *

Abstract: Some pharmacological-toxicological effects of canatoxin, a toxic protein purified from the seeds of Canavalia ensiformis have been studied in mice and rats. The most obvious effect, a lethal tonic convulsion, was generally produced 10–15 min. after intravenous injection of 2–3 mg/kg of the highly purified protein (mol. wt. 88,000). After intraperitoneal, intramuscular or subcutaneous administration the convulsion produced by the same toxin dosis occurred within 24 hours. A spinal transection at the midthoracic level did not abolish the convulsions of the hindlimbs while destruction of the medulla below this level completely blocked the convulsions of the hindlimbs. The convulsions of the head and forelimbs were unaffected by these surgical pre-treatments. The toxic protein did neither affect the isolated skeletal muscle nor did it potentiate nerve impulse induced contractions. The convulsive effect of canatoxin was potentiated by reserpine and attenuated by phenobarbital, diazepam, methenesine and also by haloperidol and spiroperidol. The total concentration of brain and spinal cord neurotransmitters seemed to remain unchanged after subconvulsive and convulsive doses of canatoxin. In the conscious rat the toxic protein did not change the blood pressure except for a shortlasting hypertensive response observed immediately before the onset of the convulsions. The heart frequency was lowered at subconvulsive and convulsive dosis but no effect was seen on the frequency of the rat isolated right atria exposed to high doses of canatoxin. The body temperature was lowered by a convulsive dosis of the toxic protein. The purified toxin did not show any haemagglutinating property or haemolytic phospholipase A2-like activity. The results strongly suggest a central nervous site for the action of canatoxin. However, if the effects are produced by the intact protein or not as well as its exact mode of action, remain unexplained.     

Effects of atorvastatin and pravastatin on glucose tolerance in diabetic rats mildly induced by streptozotocin

Effects of atorvastatin and pravastatin on glucose tolerance in mildly induced diabetic rats by streptozotocin at 24 mg/kg, i.v. were studied. Non-diabetic and diabetic rats were given orally 0.5% carboxymethylcellulose (control), 8 mg/kg atorvastatin or 8 mg/kg pravastatin once a day for 6 weeks. An oral glucose tolerance test (OGTT) was carried out 1, 2, 3, and 6 weeks after the administration. The blood glucose and plasma insulin levels measured before OGTT in the diabetic rats were not different from those in the non-diabetic rats. However, the hyperglycemic response to OGTT in the diabetic rats significantly exceeded that in the non-diabetic rats. The plasma insulin increased by OGTT in the diabetic rats appeared to be lower than that in the non-diabetic rats. Statin treatments for 1 week did not modify the OGTT-induced hyperglycemia appreciably, although there were some significant differences. More than 2 weeks after administration, the blood glucose levels at several time points after a glucose intake in the atorvastatin-treated diabetic rats were significantly higher than the respective levels in the control diabetic rats. Neither atorvastatin nor pravastatin modified the OGTT-induced insulin secretion. Statins, especially atorvastatin, may influence the glucose tolerance in mildly induced diabetic rats without alterations of insulin secretion.     

Role of the sympathetic and renin angiotensin systems in the glucose-induced increase of blood pressure in rats

The pressor effect induced by acute hyperglycemia is not well understood, therefore, it was of interest to study the effect of intravenous glucose infusion on the mean arterial pressure of anesthetized Wistar rats. Animals received glucose (100 mg/kg/min, i.v.), mannitol or saline during 30 min, but only glucose increased the mean arterial pressure (about 40 mm Hg), plasma glucose, insulin and nitric oxide (NO). Pretreatment with reserpine or indorenate (a central antihypertensive) inhibited completely the pressor effect of glucose. Reserpine also decreased the plasma NO levels. Pretreatment with ramipril or with streptozotocin decreased the late phase of the glucose-induced pressor response and the NO levels, the latter treatment also abolishes insulin plasma concentrations. The present results suggest that the pressor effect induced by glucose has an early phase due to an increase of efferent sympathetic discharges and a delayed phase produced by the activation of the renin angiotensin system.     

Lipoxygenase-mediated secretory effect of canatoxin the toxic protein from Canavalia ensiformis seeds

Canatoxin was shown to induce serotonin release from rabbit platelets and rat brain synaptosomes, as well as to release insulin from isolated pancreatic islets. All these effects were dose-dependent and were inhibited by lipoxygenase inhibitors, such as nordihydroguaiaretic acid and esculetin, but not by indomethacin, a cyclooxygenase inhibitor. The data suggest that canatoxin-induced secretory effect results from the activation of the lipoxygenase pathway which would elicit exocytosis. Thus, canatoxin might be a useful tool for the study of biological events that involve lipoxygenase mediation.