Ultrastructure and membrane permeability of cultured pancreaticβ-cells exposed to alloxan or 6-hydroxydopamine

Summary Stereological techniques on electron microscopy micrographs were used to evaluate the morphological changes of cultured islet cells that had been exposed to alloxan or 6-hydroxydopamine.Trypan Blue exclusion by cells cultured for 3 days indicated that the cells were 100% viable. Electron microscopy revealed that nearly all of the surviving cultured cells were cells.Exposure to 5 mmol/l alloxan or 1–5 mmol/l 6-hydroxydopamine for 10 or 30 min caused a general swelling of the cultured cells with a concomitant swelling of mitochondria and nuclei. The size of the secretory granules was not affected by the drugs. Only 3–10% of the cells excluded Trypan Blue after exposure to 5 mmol/l alloxan or 6-hydroxydopamine.The data conform with the hypothesis that a primary action of alloxan and 6-hydroxydopamine is at the plasma membrane level of cells.Abbreviations and definitions A _cell Cell profile area (µm²), surface area of one cell section surface - V _n Nuclear volume density (%), number of points over the nucleus divided by the number of points over the total cell area × 100 - V _m Mitochondrial volume density (%), number of points over mitochondria divided by hits over the cytoplasm (points over the cell minus points over the nucleus) × 100 - V _g Granular volume density (%), number of points over granules divided by hits over the cytoplasm × 100     

仙蜜果植物茎花果降血糖作用研究

目的:研究仙蜜果植物茎、花及果实的降血糖作用。方法:分别制得仙蜜果植物茎、花及果实的乙醇提物和茎、花的水提物;采用给予小鼠腹腔注射四氧嘧啶法建立糖尿病模型,并按体质量随机分成14组。各组小鼠给药7d后测定血糖含量、体质量、胰腺指数及胸腺指数。结果:与模型组比较,各种提取物均可降低糖尿病小鼠的血糖水平,果实85%乙醇提物和花水提物的降糖作用有极显著性差异;各种提取物对胰腺均有保护和改善作用,对免疫系统的影响不明显。结论:仙蜜果植物具有降低血糖作用,是潜在的治疗糖尿病辅助药物。     

降糖通脉无糖型颗粒对糖尿病小鼠血糖的影响

目的验证降糖通脉无糖型颗粒降血糖的作用。方法应用四氧嘧啶复制糖尿病小鼠模型,进行降血糖及糖耐量药效学试验。结果四氧嘧啶尾静脉注射3d后,所有试验的糖尿病小鼠的血糖含量均超过25mmol／L。连续给药21d后,各组小鼠血糖含量,模型对照组血糖明显高于空白对照组,降糖通脉各组和盐酸二甲双胍组明显低于模型对照组。结论降糖通脉无糖型颗粒降血糖的作用明显,并可提高糖尿病小鼠的糖耐量。     

Anti-Diabetic Activities of the Methanol Leaf Extracts of Hymenocardia Acida (Tul.) in Alloxan-Induced Diabetic Rats

The effect of methanolic extract of Hymenocardia acida leaves on diabetes and associated lipidemia were investigated on experimentally-induced diabetic rats. The extract did not demonstrate any acutely toxic effect in rats within the dose range (250 mg/kg – 2000 mg/kg) employed in the study; hence it was well tolerated by the rats. In all experiments, the anti-diabetic effects were dose-dependent and comparable to that of glibenclamide (2 mg/kg) standard. At a dose of 500 mg/kg, lipid profile markers such as the serum total cholesterol (TC) levels, LDL-C, triglycerides and HDL-C were significantly lower (p <0.05) than those of both the treated and untreated controls.     

A method for enzymatic dissociation of cells from isolated pancreatic islets

Summary An enzymatic method for isolation of single cells from the islets of Langerhans is described. The isolated cells appeared well preserved and survived for at least 7 days when maintained in culture. The dry mass of the isolated islet cells was found to be decreased 30 min after administration of alloxan to obese-hyperglycemic mice. Isolated individual islet cells from obese-hyperglycemic mice had a higher dry mass than those from their lean litter mates. Traduzione a cura di G. U.     

The effect of acute alloxan diabetes on the sensitivity of the rat skeletal neuromuscular junction to drugs

Summary Preparations from alloxan diabetic rats showed a reduced sensitivity to the neuromuscular blocking action of (+)-tubocurarine but no alteration in sensitivity to the deplolarizing neuromuscular blocking drug decamethonium. Physostigmine was less effective in augmenting twitch height in preparations from alloxan diabetic rats and such preparations had a significantly lowered total cholinesterase activity compared with control preparations. An additional observation was a reduction in the effectiveness of the pre-junctionally active agent β-bungarotoxin in producing neuromuscular blockade in physostigmine-treated preparations from alloxan diabetic rats. All the changes produced by alloxan administration were prevented by treatment with insulin.     

Myocardial injury following endogenous catecholamine release in rabbits

Catecholamines (CAT) given in large doses produce cardiomyopathic changes in several animal species. This study was designed to determine if endogenous release can also induce cardiac injury. Rabbits were infused with doses of tyramine (TYR), ranging from 200 to 500 micrograms/min/kg, i.v. for 90 min. Arterial pressure and heart rate were measured, as were total CAT concentrations, blood gases, pH and glucose. Two days later the animals were killed and cardiac injury assessed using a histological scoring system. All data were compared with controls given saline. Initial CAT averaged 452 pg/ml, rose to 2890 pg/ml after starting TYR, 500 micrograms/min/kg, and remained elevated for the duration of infusion. Circulating CAT levels were a function of TYR dose, and bore a linear relationship to the histological score (P less than 0.001). Development of lesions was unaltered by beta 1 blockade with practolol, but sharply reduced by alpha blockade with phentolamine (P less than 0.01). Pretreatment with insulin also reduced lesion formation, but diabetic (alloxan) rabbits showed no greater CAT injury. It is concluded that endogenous release of CAT induces myocardial injury in the rabbit in a dose-dependent manner. This is unrelated to myocardial O2 demand, and microvascular pathology was absent. Activation of alpha adrenergic pathways is likely the dominant or exclusive mechanism.     

Increased intestinal absorption of insulin in a micellar solution: Water-in-oil-in-water insulin micelles

Summary Water-in-oil-in-water (W/O/W) insulin micelles were prepared, and the possibility of insulin absorption in a micellar form was examined. In this preparation, insulin was trapped in oil droplets of oleic acid in glyceryl-α-monooleate. (1) W/O/W insulin micelles were absorbed from the ligated jejunal loop of rabbits to the order of 12.3 to 58.5% of the dose given (10 U/kg body weight) during the 3-h experimental period. (2) Alloxan diabetic rats were treated with intrajejunal administration of W/O/W insulin micelles at a dosage of either 25 or 50 U/100 g body weight, three times daily for as longs as 14 days. During treatment, a significant reduction in the daily excretion of urinary glucose was observed, concomitant with a decrease in fasting blood glucose. Quantitative estimates suggested that the effectiveness of 25 U/100 g of intrajejunal W/O/W insulin micelles was comparable to that of regular insulin at a dosage of 1 U/100 g i.m. These results would indicate that W/O/W insulin micelles, when given enterally, are more effective in lowering blood and urinary glucose levels than W/O/W insulin emulsions in which insulin was trapped in oil droplets of triglyceride.     

Effect of D-400, an Ayurvedic Herbal Formulation on Experimentally Induced Diabetes Mellitus

In the present study, after D-400 treatment a significant reduction in blood sugar levels in alloxan induced diabetes was observed, an oral glucose tolerance test (OGTT) showed a significant lowering of AUC in streptozotocin induced diabetes in rats. There was a rise in hepatic glycogen level closer to normal after D-400 treatment. In the pancreas of diabetic rats, D-400 therapy showed a significant increase in islet number and beta cell count and appeared to bring about blood glucose homeostasis by increasing insulin secretion through repair/regeneration of endocrine pancreas which may be responsible for the prevention of hepatic glycogenolysis.     

In vivo assessment of antidiabetic and antioxidant activities of rosemary (Rosmarinus officinalis) in alloxan-diabetic rabbits

Rosemary (Rosmarinus officinalis), used in traditional Turkish folk medicine for the treatment of hyperglycaemia, is widely accepted as one of the medicinal herb with the highest antioxidant activity. Accordingly, the present study was designed to investigate the possible actions of ethanolic extract of the leaves of Rosmarinus officinalis on glucose homeostasis and antioxidant defense in rabbits. In the first set of experiments, hypoglycaemic effects of oral administration of various doses (50, 100 and 200 mg/kg) of the extract were examined in normoglycaemic and glucose-hyperglycaemic rabbits. Optimal effect was observed in both of the animal groups with a dose of 200 mg/kg of the extract and this activity was independent from the effects of insulin. In another part of experiments, acute effect of various doses of the Rosmarinus officinalis extract on blood glucose and serum insulin levels was studied in alloxan-induced diabetic rabbits. Of the three doses of extract, the highest dose (200 mg/kg) significantly lowered blood glucose level and increased serum insulin concentration in alloxan-diabetic rabbits. The last set of experiments designed to investigate the subacute effect of the Rosmarinus officinalis extract on repeated administration in alloxan-diabetic rabbits. At the doses of 100 and 200 mg/kg, antihyperglycaemic effect of extract was accompanied by a significant increase in serum insulin levels in diabetic rabbits. Furthermore, during 1 week of treatment of diabetic rabbits with a dose of 200 mg/kg of the extract showed that the extract possessed a capability to inhibit the lipid peroxidation and activate the antioxidant enzymes. It was concluded that probably, due to its potent antioxidant properties, the Rosmarinus officinalis extract exerts remarkable antidiabetogenic effect.