Alloxan Diabetic Animals Research Articles

Rutin ameliorates nitrergic and endothelial dysfunction on vessels and corpora cavernosa of diabetic animals

Endothelial dysfunction is an early complication of diabetes and it is related to both micro- and macroangiopathies. In addition, >70% of diabetic patients develop autonomic neuropathies. Increased oxidative stress has a major role in the development of both nitrergic and endothelial dysfunction. The aim of this work is to evaluate whether rutin, a potent antioxidant, could ameliorate nitrergic and/or endothelial dysfunction in diabetic animals. Primary and secondary treatment protocols with rutin were investigated on rat aortic rings and the mesenteric arteriolar bed, and on rabbit aortic rings and corpora cavernosa (RbCC) from both euglycemic and alloxan-diabetic animals. Acetylcholine endothelium-dependent and sodium nitroprusside endothelium-independent relaxations were compared in tissues from euglycemic or diabetic animals. Electrical field stimulation (EFS)-induced relaxation was performed only in the RbCC. Endothelial-dependent relaxations were blunted by 40% in vessels and neuronal relaxation was blunted by 50% in RbCC taken from diabetic animals when compared to euglycemic animals. Pre-treatment with rutin restored both neuronal and endothelial dependent relaxations in diabetic animals towards the values achieved in control euglycemic tissues. Rutin was able to ameliorate both endothelial dysfunction and nitrergic neuropathy in animal experimental models. Rutin could be a lead compound in the primary or secondary preventive ancillary treatment of endothelial and nitrergic dysfunction in the course of diabetes.

Pituranthos tortuosus Essential Oil from Libya: Season Effect on the Composition and Antioxidant Activity

Pituranthos tortuosus has multi-local traditional applications, production of aroma, in culinary processes, killing insects and as a remedy for diabetes, infectious diseases, dyspepsia, inflammation, fever and hepatitis. The essential oil antioxidant quality and composition of the dried aerial part of P. tortuosus collected at two successive seasons (spring and summer) were investigated. Essential oils were obtained by hydrodistilla- tion, physically evaluated and analyzed by the GC-MS. The ability of the oil-batches to restore the glutathione level in the alloxan-induced diabetic rats was used to assess the antioxidant quality. A total of twenty-eight com- pounds representing 98.65 % of the 0.8 % oil-yields and nineteen compounds representing 98.39 % of the 0.3 % oil-yields were identified in the summer and spring oil-batches, respectively. The oxygenated (38.47 %) and non-oxygenated (36.31 %) monoterpenes were accumulated in the spring oil-batch. In contrast, sesquiterpenes were accumulated in the summer oil-batch which may reflects the effect of monoterpenes emission due to summer temperature and the different biosynthetic preferability of the plant during summer and spring seasons. 1,8-cineole (13.43 %), 9-epi-caryophyllene (11.62 %) and α-cadinol (21.51 %) were the major constituents of summer oil-batch, while α-thujene (21.22 %) and linalool (27.98 %) were major components of spring oil- batch. The glutathione level was restored significantly (P< 0.05) in the animal treated with summer (33.6 %) and spring (32.8 %) oil-batches compared to the alloxan diabetic animals (21.3 %). In conclusion, major chemical changes were recognized in the summer and spring volatile oil-batches evidenced by the variations in the percentages of the monoterpenes and sesquiterpenes in these oil-batches which affect the antioxidant quality of the oils.

Function and Gene Expression of Islets Experimentally Transplanted to Muscle and Omentum

Islet transplantation to the liver is a potential curative treatment for patients with type 1 diabetes. Muscle and the greater omentum are two alternative implantation sites, which can provide excellent engraftment and hold potential as future sites for stem-cell-derived beta-cell replacement. We evaluated the functional outcome after islet transplantation to muscle and omentum and found that alloxan-diabetic animals were cured with a low number of islets (200) at both sites. The cured animals had a normal area under the curve blood glucose response to intravenous glucose, albeit animals with intramuscular islet grafts had increased 120-min blood glucose levels. They also demonstrated an exaggerated counter regulatory response to hypoglycemia. The expression of genes important for beta-cell function was, at both implantation sites, comparable to that in native pancreatic islets. The gene expression of insulin (INS1 and INS2) and glucose transporter-2 was even increased, and the expression of lactate dehydrogenase decreased, at both sites when compared to native islets. We conclude that muscle and omentum provide excellent conditions for engraftment of transplanted islets. When compared to control, 200 islets implanted to the omentum displayed a restored glucose tolerance, whereas animals with intramuscular islet grafts of similar size displayed mild glucose intolerance.

Evaluation of the Anti-Diabetic and Anti-Ulcer Properties of Some Jordanian and Iraqi Medicinal Plants; a Screening Study

A large number of Jordanian and Iraqi medicinal plants have been used in traditional medicine for hypoglycemic and anti-ulcer activities. We have started a screening program to evaluate the activity of some of these plants and their extracts taking in consideration their use as an alternative therapy. Various parts of several plants were extracted and the hypoglycemic effects of the aqueous extracts have been examined in normal, glucose loaded and alloxan diabetic experimental animals. Teucrium polium aqueous extract was studied for its anti-ulcer activity of ulcers induced in rats by starvation and reserpine and/or stress. The aqueous extract of the aerial parts of Artemisia herba alba was administered orally to normoglycemic and alloxan diabetic rabbits and rats and found to produce a significant hypoglycemic activity (normoglycaemic: plasma glucose levels reduced from 116±4 to 90±3mg/dL after 90minutes, p<0.001; diabetic animals from 471±7 to 399±9mg/dL, p<0.001). The aerial aqueous extract of Phangnalon rupestre, Sinapis arvensis and Eryngium creticum also exhibited significant hypoglycemic effects in euglycaemic and glucose loaded rats. The other plants examined (Ditrichia graveolens, Alkanna strigosa, , Centaurea iberica, Asphodelin lutea, Paronychia argentea, rosmarinus officinalis, Achillea santolina, Achillea micrantha, Allium sativum, Centaurea phyllacephala, Centaurea behen, Crataegus azarolus, Prosopis farcta and Myrtus communis) failed to produce a significant change in the plasma glucose levels. One herb was comprehensively tested in detail for its anti-ulcer activity; Teucrium polium aqueous extract (intraperitoneally;150mg/kg) produced an average of 50% healing of ulcers where as the orally administered extract produced 85% healing activity of ulcers when compared with the controls.

English

Urtica dioica&nbsp;has been shown to have capability of reducing blood glucose through enhancing insulin secretion. The aim of this study was to assess&nbsp;in vivo&nbsp;and&nbsp;in vitroeffects of aqueous and alcoholic extracts of&nbsp;U. dioica&nbsp;leaves on activities of Acetyl coenzyme A carboxylase (ACC), Nucleoside diphosphate kinase (NDPK) and insulin level and serum glucose concentration. The experimental animals were randomly distributed among 6 groups of 7 or 8 rats each. The treatment groups received 150 mg/kg of alloxan. Then rats were fed alcoholic and aqueous extracts of&nbsp;U. dioica&nbsp;at 50 mg/kg/day doses for a period of two weeks. Subsequently glucose, insulin levels, and ACC, NDPK activity were measured. Our studies showed significantly lower levels of glucose in the group of rats that were treated with ethanol extract of&nbsp;U. dioica&nbsp;leaves as compared with the control group (279.6 &plusmn; 24.3 vs. 393.6 &plusmn; 24.9 mg/dl), (p&lt;0.01). Present results showed significantly elevated levels of insulin in the group of rats treated with ethanol extract of&nbsp;U. dioica&nbsp;leaves as compared with the control group (7.6 &plusmn; 0.3 vs. 3.6 &plusmn; 0.2, &micro;g/l), (p&lt;0.01). Also, results showed significantly elevated activity of ACC and NDPK in the group of rats treated with ethanol and aqueous extract of&nbsp;U. dioica&nbsp;leaves as compared with the control group. The results of the present study indicated that alcoholic extract of&nbsp;U. dioica&nbsp;leaves was found to reduce glucose level and increase insulin secretion, ACC and NDPK activity in the alloxan diabetic animals. &nbsp; Key words:&nbsp;Urtica dioica, acetyl coenzyme A carboxylase, extract, nucleoside diphosphate kinase.

Acid Amyloglucosidase and Carbohydrate Regulation

High activity of the exoamylolytic enzyme, acid amyloglucosidase, was found in isolated pancreatic islets of the mouse. Enzyme activity was optimum at pH 5.0-5.5 and the activity at pH 5.0 was two times that of liver and ten times that of skeletal muscle. Acid amyloglucosidase activity in islets isolated from alloxan diabetic animals was reduced to about 10% of the normal value indicating that the major part of the enzyme activity is confined to islet β-cells. In contrast, islets isolated from insulin-hypersecreting obese mice (AO-mice) were found to have markedly elevated levels of acid amyloglucosidase activity.

The antidiabetic activity of total lignan from Fructus Arctii against alloxan‐induced diabetes in mice and rats

The antidiabetic activity of the total lignan from the plant Fructus Arctii, used in China for the control of diabetes, was investigated in models of alloxan-induced diabetic mice and hyperglycemic-hyperlipidemic diabetic rats. The biochemical parameters studied were: blood glucose, glucose tolerance, serum insulin, serum triglycerides, total cholesterol and high density lipoprotein (HDL). Total lignan was given to mice and rats daily for 10 days at doses of 2.0, 1.0, 0.5 g/kg and 1.38, 0.69, 0.35 g/kg respectively. The alloxan-diabetic animals showed significant reductions in plasma glucose, triglycerides and total cholesterol after treatment with the total lignan from the plant Fructus Arctii and glibenclamide (used as standard) compared with the diabetic controls, while the glucose tolerance, serum insulin level and HDL-cholesterol were elevated without the risk of hypoglycemia. In conclusion, the total lignan from the plant Fructus Arctii has been proven to be a safer antidiabetic agent and might help to prevent diabetic complications. It can serve as a good adjuvant in the present armamentarium of antidiabetic drugs.

Hypoglycemic and Antilipidperoxidative Effects of a Polyherbal Formulation, Diakyur, in Experimental Animal Models

The present study investigates the effect of Diakyur, a polyherbal formulation composed of powder of Cassia javanica and dried, standardised aqueous extracts of Cassia auriculata, Salacia reticulata, Gymnema sylvestre, Mucuna pruriens, Syzygium jambolanum, Terminalia arjuna on blood glucose level of normal and diabetic animals as well as lipid peroxide level in normal and 28 day drug treated diabetic rats. The raw materials and the formulation were standardised by high performance thin layer chromatography (HPTLC) and high pressure liquid chromatography (HPLC) method of analysis. The hypoglycemic activity and glucose tolerance test were studied in normal and alloxan (150 mg/kg, i.p) induced diabetic rats and rabbits after administration of Diakyur at the dose of 1600 mg/kg, p.o. Blood glucose level was determined by O-toluidine method. Lipid peroxide levels of plasma, erythrocyte membrane, liver and kidney tissues were studied in alloxan induced diabetic rats after 28 days drug treatment. At the dose of 1600 mg/kg, p.o Diakyur showed a hypoglycemic effect at varying degree of significance (p < 0.05‐ 0.001) in normal as well as alloxan induced diabetic rats and rabbits in comparison with respective control groups. Diakyur treatment in the glucose tolerance test showed the maximum effect at 180th min of glucose administration in both normal and alloxan diabetic animals. The drug treated alloxan diabetic rats showed significant (p < 0.001) reduction in plasma, erythrocyte membrane, liver and kidney lipid per

In vivo effect ofTrigonella foenum graecumon the expression of pyruvate kinase, phosphoenolpyruvate carboxykinase, and distribution of glucose transporter (GLUT4) in alloxan-diabetic rats

Plasma glucose levels are maintained by a precise balance between glucose production and its use. Liver pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK), 2 key enzymes of glycolysis and gluconeogenesis, respectively, play a crucial role in this glucose homeostasis along with skeletal muscle glucose transporter (GLUT4). In the diabetic state, this balance is disturbed owing to the absence of insulin, the principal factor controlling this regulation. In the present study, alloxan-diabetic animals having high glucose levels of more than 300 mmol/L have been taken and the administration of Trigonella seed powder (TSP) to the diabetic animals was assessed for its effect on the expression of PK and PEPCK in liver and GLUT4 distribution in skeletal muscle of alloxan-diabetic rats. TSP treatment to the diabetic animals resulted in a marked decrease in the plasma glucose levels. Trigonella treatment partially restored the altered expression of PK and PEPCK. TSP treatment also corrected the alterations in the distribution of GLUT4 in the skeletal muscle.

A new tactic to treat postprandial hyperlipidemia in diabetic rats with gastroparesis by improving gastrointestinal transit

Improvement of gastrointestinal transit was thought to be a new tactic to treat postprandial hypertriglyceridemia in diabetic individuals with gastroparesis. Diabetic gastroparesis, lipid load testing, and the effect of domperidone or aqueous extract of rhizomes of Rheum palmatum L. on postprandial hypertriglyceridemia were evaluated in alloxan-induced diabetic rats. Alloxan diabetic animals had a slow gastrointestinal transit, together with delayed and exaggerated postprandial hypertriglyceridemia, after oral administration of olive oil, which was significantly improved after oral administration of domperidone or R. palmatum L. However, atropine could prevent the effects of R. palmatum L. The reduced postprandial hypertriglyceridemia was highly correlated with the improvement in gastrointestinal transit. These results suggest that promotion of gastrointestinal transit may be useful for the treatment of postprandial hypertriglyceridemia in diabetic patients with gastroparesis. R. palmatum L. may become a new choice for these patients since it has more potential benefits than domperidone.

Differential effects of vanadium, tungsten and molybdenum on inhibition of glucose formation in renal tubules and hepatocytes of control and diabetic rabbits: beneficial action of melatonin and N-acetylcysteine.

Effect of vanadyl acetylacetonate (VAc), tungstate and molybdate on gluconeogenesis has been studied in isolated hepatocytes and kidney-cortex tubules. In renal tubules of control and alloxan-diabetic animals, the rank order of the metal-compounds-induced (i) inhibition of glucose formation from alanine+glycerol+octanoate or aspartate+glycerol+octanoate, (ii) decrease in the mitochondrial membrane potential (delta psim), (iii) increase in the hydroxyl free radicals (HFR) generation and (iv) decline in glucose-6-phosphatase activity was the following: VAc > tungstate > molybdate. Moreover, in contrast to VAc, both tungstate and molybdate at 100 microM concentration did not practically decrease glucose production in hepatocytes isolated from diabetic rabbits, and significantly increased the rate of lactate formation in renal tubules. N-acetylcysteine at 2 mM concentration partially attenuated vanadium-induced alterations in glucose formation, delta psim and the cellular glutathione redox state, whereas 0.1 mM melatonin did not abolish vanadium-induced changes in gluconeogenesis despite attenuation of vanadium effects on HFR formation and delta psim decline. However, similarly to control rabbits, following 6 days of intraperitoneal administration of both VAc (1.275 mg V/kg body weight daily) and melatonin (1 mg/kg body weight daily) to alloxan-diabetic animals, vanadium-induced elevated serum creatinine and urea levels were decreased, indicating the beneficial effect of melatonin on diabetes- and vanadium-induced nephrotoxicity in rabbits. As serum glucose levels were also significantly diminished by vanadium+melatonin treatment of diabetic animals, the combination therapy of vanadium compounds and melatonin needs a careful evaluation.

Protective effects of sodium orthovanadate in diabetic reticulocytes and ageing red blood cells of Wistar rats.

The reticulocytes and the ageing red blood cells (RBCs) namely young (Y), middle-aged (M) and old RBCs (O) of female Wistar rats from different groups such as control animals (C), controls treated with vanadate (C + V), alloxan-induced diabetic (D), diabetic-treated with insulin (D + I) and vanadate (D + V), were fractionated on a percoll/BSA gradient. The following enzymes were measured - hexokinase (HK), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione-s-transferase (GST), alanine aminotransferase (AlaAT), aspartate aminotransferase (AsAT) and arginase in the hemolysates of all the RBCs fractions. Decreases in the activity of HK and AsAT by about 70%, arginase and GSH-Px by 30% in old RBCs were observed in comparison to reticulocytes of control animals. Increases in the activity of GSSG-R by 86%, AlaAT by more than 400% and GST by 70% were observed in old RBCs in comparison to reticulocytes of control animals. Alloxan diabetic animals showed a further decrease in the activities of HK in Y RBCs by 37%, M RBCs by 39% and O RBCs by 32%, GSH-Px activity in Y RBCs by 13%, M RBCs by 20% and O RBCs by 33% and GST activity in Y RBCs by 14%, M RBCs by 42% and O RBCs by 60% in comparison to their corresponding cells of control animals. An increase in the activity of all the enzymes studied was also observed in reticulocytes of diabetic animals in comparison to reticulocytes of controls. The GSSG-R activity was found to be increased in Y RBCs by 49%, M RBCs by 67% and O RBCs by 64% as compared to the corresponding age-matched cells of control animals. The activity of arginase also decreased in Y RBCs by about10%, M RBCs by 20% and O RBCs by 30% in comparison to the age-matched cells of control animals. A decrease in the activity of AsAT in Y and M RBCs by 30%, and O RBCs by 25% was observed in diabetic animals in comparison to the age-matched cells of control animals. The activity of AlaAT was found to be decreased by more than 10% in Y and M RBCs and 25% in O RBCs of diabetic animals in comparison to the age-matched cells of control animals. Insulin administration to diabetic animals reversed the altered enzyme activity to control values. Vanadate treatment also reversed the enzyme levels except for that of GST in old cells.

Inhibition of gluconeogenesis by vanadium and metformin in kidney-cortex tubules isolated from control and diabetic rabbits

Effect of vanadyl acetylacetonate (VAc) and metformin on gluconeogenesis has been studied in isolated hepatocytes and kidney-cortex tubules of rabbit. Glucose formation from alanine+glycerol+octanoate, pyruvate or dihydroxyacetone was inhibited by 50–80% by 100 μM VAc or 500 μM metformin in renal tubules of control and alloxan-diabetic animals, while the inhibitory action of these compounds in hepatocytes was less pronounced (by about 20–30%). In contrast to VAc, metformin increased the rate of lactate formation by about 2-fold in renal tubules incubated with alanine+glycerol+octanoate. In view of VAc-induced changes in intracellular gluconeogenic intermediates and gluconeogenic enzyme activities, it is likely that this compound may decrease fluxes through pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase and glucose-6-phosphatase. In contrast to VAc, metformin-induced decrease in renal gluconeogenesis may result from a decline of cytosolic oxaloacetate level and consequently PEPCK activity. Following 6 days of VAc administration (1.275 mg V kg −1 body weight daily) the blood glucose level in alloxan-diabetic rabbits was normalised while blood glucose changes in control animals were not observed. On the contrary, in diabetic animals treated for 6 days with metformin (200 mg kg −1 body weight day −1) a high blood glucose level was maintained. Unfortunately, VAc-treated control and diabetic rabbits exhibited elevated serum urea and creatinine levels. In VAc-treated animals vanadium was accumulated in kidney-cortex up to 7.6±0.6 μg V g −1 dry weight. In view of a potential vanadium nephrotoxicity a therapeutic application of vanadium compounds needs a critical re-evaluation.

In Vivo and in Vitro Effects of Adenosine-5???-0-(2-thiodiphosphate) on Pancreatic Hormones in Dogs

Adenosine-5'-O-(2-thiodiphosphate) (ADP beta S), a P2y purinergic agonist, has been shown to be a potent insulin secretagogue on the isolated rat pancreas. In the present work the effects of ADP beta S on insulin somatostatin, and glucagon secretions were investigated in dogs. In vivo, in anesthetized fasted dogs, i.v. ADP beta S (0.1 mg kg-1) induced an immediate increase in insulin and somatostatin-like immunoreactivity (SLI) but not in glucagon pancreaticoduodenal outputs. In conscious fasted dogs, i.v. ADP beta S (0.1 mg kg-1) produced an immediate and transient augmentation in plasma insulin levels but not in plasma SLI and glucagon levels. In vitro, the effects of ADP beta S were investigated on the isolated uncinate process of dog pancreas, from normal and alloxan-diabetic animals. In normal uncinate process, in presence of 8.3 mM glucose, ADP beta S (1 microM) stimulated insulin and SLI releases but not glucagon release. On uncinate process from diabetic animals, ADP beta S (1 microM) retained its stimulating effects but the responses were impaired as compared with normal dogs: Insulin response was drastically diminished and SLI response strongly enhanced. In conclusion, ADP beta S is a potent insulin secretory agent in dog. This P2y purinoceptor agonist, which exerts a direct stimulatory effect on pancreatic SLI, is interestingly devoid of direct glucagonotropic properties.

Favourable effect of tryptophan/insulin treatment on serotoninergic imbalance in alloxan diabetic rats

1. 1. The effects of insulin and/or tryptophan (Try) administration on Try, serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA) in raphe nuclei and hypothalamus and serum levels of large neutral amino acids [Try, valine, isoleucine, leucine, tyrosine and phenylalanine, (LNAA)] was investigated in diabetic rats. 2. 2. Alloxan diabetic animals (15 days) were treated up to 45 days with l-Try (50 mg/kg i.p., daily) and/or insulin (4 I.U./rat, daily). 3. 3. In saline treated diabetic rats a significant decrease in Try and significant increase in 5-HT concentrations was observed in the raphe nuclei and hypothalamus, while the values of 5-HIAA were significantly increased only in the raphe nuclei as compared to the nondiabetic, saline treated control rats. 4. 4. The administration of Try in combination with insulin to diabetic rats altered the levels of brain Try, 5-HT, 5-HIAA and serum concentrations of valine, leucine and isoleucine towards the values in the control (nondiabetic) group. 5. 5. Our results suggest that simultaneous use of Try and insulin has positive effect on the alterations in Try and 5-HT metabolism, that occurred in long-term alloxan diabetic rats despite insulin application.

Adrenergic activation of glycogen phosphorylase in primary culture diabetic cardiomyocytes.

The basis of catecholamine-induced activation of glycogen phosphorylase was investigated in adult rat cardiomyocytes isolated from normal and alloxan-diabetic animals. Cells derived from diabetic animals exhibited a hypersensitive response to epinephrine stimulation that was apparent 3 h after cell isolation and was further enhanced on maintenance of the myocytes in culture for 24 h. Normal cells initially lacked the hypersensitive response to epinephrine stimulation, although on maintenance of these cells in culture for 24 h, the hypersensitive response was acquired in vitro. To assess alpha- and beta-adrenergic mediation of the response, normal and diabetic cardiomyocytes were incubated with propranolol, a beta-blocker, before direct alpha 1-receptor stimulation with phenylephrine. Both normal and diabetic myocytes failed to undergo activation of phosphorylase in 3- or 24-h cell cultures. In addition, the effects of epinephrine on phosphorylase activation were completely inhibited by propranolol, whereas prazosin, an alpha-blocker, was unsuccessful. The present data suggest that the hypersensitive response of glycogen phosphorylase in normal and diabetic cardiomyocytes is solely mediated through beta-adrenergic receptor activation.

Post-receptor defect accounts for phosphorylase hypersensitivity in cultured diabetic cardiomyocytes.

The basis for the hypersensitive response of glycogen phosphorylase to epinephrine stimulation was investigated in adult rat cardiomyocytes isolated from normal and alloxan-diabetic animals. To assess potential G-protein involvement in the response, normal and diabetic derived myocytes were incubated with either cholera or pertussis toxin prior to hormonal stimulation. Pretreatment of cardiomyocytes with cholera toxin resulted in a potentiated response to epinephrine stimulation whereas pertussis toxin did not affect the activation of this signaling pathway. To determine if the enhanced response of phosphorylase activation resulted from an alteration in adenylate cyclase activation, the cells were challenged with forskolin. After 3 hr in primary culture, diabetic cardiomyocytes exhibited a hypersensitive response to forskolin stimulation relative to normal cells. However, after 24 hr in culture, both normal and diabetic myocytes responded identically to forskolin challenge. The present data suggest that a cholera toxin sensitive G-protein mediates the hypersensitive response of glycogen phosphorylase to catecholamine stimulation in diabetic cardiomyocytes and this response which is present in alloxan-diabetic cells and is induced in vitro in normal cardiomyocytes is primarily due to a defect at a post-receptor site.

Hypoglycemic activity op several seaweed extracts

The hypoglycemic activity of several seaweed extracts on rabbits was studied. Ethanol extracts of Laminaria ochroleuca, Saccorhiza polyschides and Fuctis vesiculosus were administered orally to normal animals and their effects on glycemia and triglyceridemia evaluated. Crude polysaccharides and protein solutions from Himanthalia elongata and Codium tomentosum were also assayed. Polysaccharides and proteins from H. elongata caused a significant reduction in blood glucose 8 h after intravenous administration. A dose of 5 mg/kg of crude polysaccharide lowered glycemia about 18% in normal rabbits and by about 50% in alloxan-diabetic animals, while the protein solution lowered glycemia in diabetic rabbits by about 30%.

Dissociation of adenosine from metabolic regulation of coronary flow in the lamb.

The objective of these studies was to evaluate the contribution of an adenosine mechanism to metabolic regulation of coronary flow. Cardiac O2 metabolism (MVO2) was altered by changing cardiac output while aortic pressure and heart rate were held constant (paced). Ganglionic (tetraethylammonium chloride) and beta blockade (propranolol) were employed. Relationships of coronary flow to MVO2 were determined in control and alloxan diabetic animals. The latter have previously been shown to have reduced sensitivity to adenosine [Am. J. Physiol. 243 (Heart Circ. Physiol. 12): H252-H258, 1982]. In each group, responses were measured before and after adenosine receptor blockade with aminophylline (10 mg/kg). Responses to infused adenosine were also compared. A linear relationship between adenosine infusion rate and flow was found in all conditions. Aminophylline caused a 70% reduction in adenosine sensitivity in controls. In the diabetics, adenosine sensitivity was much reduced and was identical with blocked controls. A close correlation between left ventricular work and MVO2 was found in both groups. Coronary flow increased linearly with MVO2, and the slopes before and after aminophylline were identical. Myocardial O2 extraction remained unchanged. The same relationships were found in the diabetics, and responses did not differ from controls. Thus, in two conditions of sharply reduced sensitivity to exogeneous adenosine, coronary flow (and resistance) were as equally well matched to MVO2 as in controls. These data suggest that mechanisms other than, or in addition to, adenosine provide the close link between MVO2 and coronary flow with changing cardiac work loads.

Effect of acute hypoxia on cardiac function in alloxan-diabetic dogs.

The aim of the present study was to examine the left ventricular and haemodynamic parameters during acute hypoxia induced by carbon monoxide intoxication and/or after norepinephrine administration in metabolically healthy and alloxan-diabetic dogs. In metabolically healthy animals after carbon monoxide intoxication followed by norepinephrine administration myocardial oedema occurred with a concomitant elevation of diastolic stiffness in the left ventricular wall, resulting in impaired cardiac performance. In the alloxan-diabetic animals no myocardial oedema developed and therefore no further increase of the originally elevated left ventricular diastolic stiffness could be observed. Close correlations were demonstrable between the enhanced water content and diastolic stiffness of the left ventricular wall in metabolically healthy animals as well as between the myocardial contractile force and cardiac output index in both control and diabetic dogs. In contrast to the controls, following norepinephrine administration per se decrease of cardiac performance could be observed in the alloxan-diabetic animals. Based on these results, it can be concluded that an increase of left ventricular diastolic stiffness impairs the cardiac performance in acute hypoxia following norepinephrine administration both in control and in diabetic animals, even if different reasons are responsible for it.