Improvement in cardiac function in streptozotocin-diabetic rats by salt loading

1994 ◽  
Vol 72 (11) ◽  
pp. 1288-1293 ◽  
Author(s):  
Soter Dai ◽  
Heather Fraser ◽  
Violet G. Yuen ◽  
John H. McNeill

Effects of salt loading by drinking 0.9% NaCl solution on the myocardial performance in nondiabetic and diabetic Wistar rats were studied using the isolated working heart apparatus. Body weight and fluid and food intakes of these animals were monitored. Blood pressure and plasma levels of glucose, insulin, cholesterol, and triglycerides were also measured. Diabetes was induced by intravenous injection of streptozotocin (60 mg/kg). Diabetic rats were found to develop myocardial dysfunction at 8 weeks after STZ injection, accompanied by significant increases in food and fluid intakes, slowed body weight gain, hyperglycemia, hypoinsulinemia, and hyperlipidemia but without significant changes in blood pressure. Salt loading did not cause significant changes in any of the parameters studied in nondiabetic rats. However, in streptozotocin-diabetic rats given saline to drink, the impaired myocardial function was significantly improved and was associated with a significant reduction in hyperphagia and hyperlipidemia. Plasma glucose levels significantly decreased at weeks 1–3 but increased to the levels of untreated diabetic animals at weeks 4–7. There was an increase in fluid intake, but neither blood pressure nor plasma insulin levels were significantly affected. It is suggested that the improvements in cardiac function and hyperlipidemia in diabetic rats by salt loading may be related to each other; however, the mechanisms for these effects are not clear but are unlikely to be due to changes in glycemic control.Key words: streptozotocin diabetes, salt loading, cardiac dysfunction.

1992 ◽  
Vol 70 (12) ◽  
pp. 1583-1589 ◽  
Author(s):  
Soter Dai ◽  
John H. McNeill

The present study compares the cardiovascular consequences of a 6-week fructose feeding in nondiabetic and streptozotocin-diabetic rats. Myocardial performance of these animals was determined using the isolated perfused working heart preparation. Systolic blood pressure, pulse rate, ventricular weight/body weight ratio, and plasma levels of glucose, insulin, triglycerides, and cholesterol were measured. In nondiabetic rats, fructose drinking caused significant increases in blood pressure, pulse rate, and plasma concentrations of insulin and triglycerides. Streptozotocin-diabetic animals exhibited significantly less body weight growth, slower pulse rate, higher plasma levels of cholesterol and triglycerides, ventricular enlargement, and functional impairment of the myocardium. The fructose-loaded diabetic rats had larger increases in plasma cholesterol and triglycerides than did control fructose-fed rats, but the fructose-induced increases in blood pressure and pulse rate were attenuated significantly. However, plasma levels of glucose and insulin and the degree of ventricular enlargement and myocardial dysfunction were not significantly different from those of control diabetic rats. These results show that fructose loading for 6 weeks can cause increases in blood pressure, pulse rate, and plasma lipids in both nondiabetic and diabetic rats. However, fructose ingestion does not significantly alter glycemic control or affect the development of myocardial dysfunction in streptozotocin-diabetic rats.Key words: fructose, diabetes, hypertension, hyperlipidemia, myocardial dysfunction.


2019 ◽  
Vol 19 (4) ◽  
pp. 503-510 ◽  
Author(s):  
Mohamed Eddouks ◽  
Farid Khallouki ◽  
Robert W. Owen ◽  
Morad Hebi ◽  
Remy Burcelin

Aims: Arganimide A (4,4-dihydroxy-3,3-imino-di-benzoic acid) is a compound belonging to a family of aminophenolics found in fruit of Argania spinosa. The purpose of this study was to investigate the glucose and lipid lowering activity of Arganimide A (ARG A). Methods: The effect of a single dose and daily oral administration of Arganimide A (ARG A) on blood glucose levels and plasma lipid profile was tested in normal and streptozotocin (STZ) diabetic rats at a dose of 2 mg/kg body weight. Results: Single oral administration of ARG A reduced blood glucose levels from 26.50±0.61 mmol/L to 14.27±0.73 mmol/L (p<0.0001) six hours after administration in STZ diabetic rats. Furthermore, blood glucose levels were decreased from 5.35±0.30 mmol/L to 3.57±0.17 mmol/L (p<0.0001) and from 26.50±0.61 mmol/L to 3.67±0.29 mmol/L (p<0.0001) in normal and STZ diabetic rats, respectively, after seven days of treatment. Moreover, no significant changes in body weight in normal and STZ rats were shown. According to the lipid profile, the plasma triglycerides levels were decreased significantly in diabetic rats after seven days of ARG treatment (p<0.05). Moreover, seven days of ARG A treatment decreased significantly the plasma cholesterol concentrations (p<0.001). Conclusion: ARG A possesses glucose and lipid-lowering activity in diabetic rats and this natural compound may be beneficial in the treatment of diabetes.


1985 ◽  
Vol 106 (2) ◽  
pp. 225-231 ◽  
Author(s):  
A.-M. Mendes ◽  
R. J. Madon ◽  
D. J. Flint

ABSTRACT Cortisol implants in normal and diabetic rats reduced body weight, adiposity, insulin receptor concentration and both basal and insulin-stimulated rates of lipogenesis in isolated adipocytes, whilst insulin sensitivity was unchanged. In normal but not diabetic rats these changes were accompanied by increased serum glucose and insulin concentrations. In contrast, progesterone implants in normal and diabetic rats increased body weight gain, adiposity, insulin receptor concentration and both basal and insulin-stimulated rates of lipogenesis in adipose tissue, again without affecting insulin sensitivity. Progesterone did not affect serum insulin concentrations in normal or diabetic rats but accelerated the decline in serum glucose concentrations which occurred during an overnight fast in diabetic rats. The results suggest that (1) cortisol inhibits lipogenesis in adipose tissue without affecting insulin sensitivity, (2) cortisol reduces insulin binding in adipose tissue without a requirement for hyperinsulinaemia, which might itself indirectly lead to down-regulation of the insulin receptor, and (3) in diabetic rats progesterone stimulates lipogenesis in adipose tissue without any increase in food intake or serum insulin concentrations suggesting that progesterone may have a direct anabolic role in adipose tissue. J. Endocr. (1985) 106, 225–231


1993 ◽  
Vol 71 (3-4) ◽  
pp. 270-276 ◽  
Author(s):  
Violet G. Yuen ◽  
Chris Orvig ◽  
Katherine H. Thompson ◽  
John H. McNeill

Decreased cardiac function in streptozotocin-diabetic rats has been used as a model of diabetes-induced cardiomyopathy, which is a secondary complication in diabetic patients. The present study was designed to evaluate the therapeutic effect of a new organic vanadium complex, bis(maltolato)oxovanadium(IV), (BMOV), in improving heart function in streptozotocin-diabetic rats. There were four groups of male, Wistar rats: control (C), control treated (CT), diabetic (D), and diabetic treated (DT). Treatment consisted of BMOV, 0.5 mg/mL (1.8 mM) for the first 3 weeks and 0.75 mg/mL (2.4 mM) for the next 22 weeks, in the drinking water of rats allowed ad libitum access to food and water. BMOV lowered blood glucose to < 9 mM in 70% of DT animals without any increase in plasma insulin levels, and mean blood glucose and plasma lipid levels were significantly lower in DT vs. D rats. Tissue vanadium levels were measured in plasma, bone, kidney, liver, muscle, and fat of BMOV-treated rats. Plasma vanadium levels averaged 0.84 ± 0.07 μg/mL (16.8 μM) in CT rats and 0.76 ± 0.05 μg/mL (15.2 μM) in DT animals. The highest vanadium levels at termination of this chronic feeding study were in bone, 18.3 ± 3.0 μg/g (0.37 μmol/g) in CT and 26.4 ± 2.6 μg/g (0.53 μmol/g) in DT rats, with intermediate levels in kidney and liver, and low, but detectable levels in muscle and fat. There were no deaths in either the CT or DT group, and no overt signs of vanadium toxicity were present. Tissue vanadium levels were not correlated with the glucose-lowering effect. Isolated working heart parameters of left ventricular developed pressure (LVDP) and rate of pressure development (+dP/dT, and −dP/dT) indicated that BMOV treatment resulted in significant correction of the heart dysfunction associated with streptozotocin-induced diabetes in rat.Key words: bis(maltolato)oxovanadium(IV), vanadium, diabetes, streptozotocin, myocardial dysfunction.


2004 ◽  
Vol 47 (4) ◽  
pp. 545-551 ◽  
Author(s):  
Ricardo Galletto ◽  
Vera Lúcia Dias Siqueira ◽  
Edilene Bega Ferreira ◽  
Arildo José Braz Oliveira ◽  
Roberto Barbosa Bazotte

In this study we investigated the antidiabetic and hypolipidemic potential of dried powdered leaves of Gymnema sylvestre (GS). The acute effect of GS administered by oral gavage on glucose blood level of and lipids in non-diabetic and alloxan-diabetic rats were investigated in the following conditions: a) after a balanced meal; b) after the ingestion of 1000 mg/kg amylose or 1000 mg/kg glucose; c) after the ingestion of a mixture of 12 mL/kg soybean oil + 1% cholesterol (SOC). In addition, the effect of the treatment with GS during two (sub-acute) or four weeks (chronic) on body weight, food and water ingestion, glucose blood level and lipids in non-diabetic and alloxan-diabetic rats were measured. The dose of GS utilized in the majority of the experiments, i.e., 30 mg/kg, corresponds to that given to treat diabetes in Brazil. GS acutely did not influence the elevation of glycemia promoted by a balanced meal or by the administration of amylose or glucose; but promoted more intense (P<0.05) elevation of serum lipids after the administration of SOC. Moreover, the sub-acute and chronic treatment with GS in non-diabetic and alloxan-diabetic rats did not change: a) the body weight gain; b) food and water ingestion; c) the blood level of glucose and lipids. Thus we concluded that GS, at least in the form commercialized in the Brazil, i.e., dried powdered leaves, require further experimental and clinical trials before being recommended to treat diabetes and hyperlipidemia.


Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 4
Author(s):  
Fotini Filippopoulou ◽  
George I. Habeos ◽  
Vagelis Rinotas ◽  
Antonia Sophocleous ◽  
Gerasimos P. Sykiotis ◽  
...  

Glucocorticoids are used widely on a long-term basis in autoimmune and inflammatory diseases. Their adverse effects include the development of hyperglycemia and osteoporosis, whose molecular mechanisms have been only partially studied in preclinical models. Both these glucocorticoid-induced pathologies have been shown to be mediated at least in part by oxidative stress. The transcription factor nuclear erythroid factor 2-like 2 (NRF2) is a central regulator of antioxidant and cytoprotective responses. Thus, we hypothesized that NRF2 may play a role in glucocorticoid-induced metabolic disease and osteoporosis. To this end, WT and Nrf2 knockout (Nrf2KO) mice of both genders were treated with 2 mg/kg dexamethasone or vehicle 3 times per week for 13 weeks. Dexamethasone treatment led to less weight gain during the treatment period without affecting food consumption, as well as to lower glucose levels and high insulin levels compared to vehicle-treated mice. Dexamethasone also reduced cortical bone volume and density. All these effects of dexamethasone were similar between male and female mice, as well as between WT and Nrf2KO mice. Hepatic NRF2 signaling and gluconeogenic gene expression were not affected by dexamethasone. A 2-day dexamethasone treatment was also sufficient to increase insulin levels without affecting body weight and glucose levels. Hence, dexamethasone induces hyperinsulinemia, which potentially leads to decreased glucose levels, as well as osteoporosis, both independently of NRF2.


Author(s):  
M. James C. Crabbe ◽  
B. Üstündag ◽  
M. Cay ◽  
M. Naziroglu ◽  
N. Ilhan ◽  
...  

1986 ◽  
Vol 251 (3) ◽  
pp. H571-H580 ◽  
Author(s):  
B. Rodrigues ◽  
J. H. McNeill

The isolated perfused working heart was used to study hypertensive diabetes-induced alterations in cardiac function at 6 and 12 wk after diabetes was induced. At 6 wk after diabetes induction, cardiac performance was depressed in the diabetic animals. However, there was no difference in cardiac function between normotensive Wistar and spontaneously hypertensive (SHR) diabetic rats. Wistar-Kyoto (WKY) rats were also included as normotensive controls in our 12-wk study. Hearts from 12-wk SHR and Wistar diabetic animals exhibited a depressed left ventricular developed pressure and positive and negative dP/dt when compared with control animals. However, this depression was not seen in the WKY diabetic animals. In addition, quantitation of various parameters of heart function revealed highly significant differences between SHR diabetic animals and all other groups associated with an increased mortality. Serum lipids were elevated in SHR and Wistar and were unaffected in WKY diabetic rats. Furthermore, thyroid hormone levels were not depressed in WKY diabetic rats as seen in the other two diabetic groups. This normal lipid metabolism and thyroid status could, in part, explain the lack of cardiac dysfunction in these animals. The data provide further evidence that the combination of hypertension and diabetes mellitus produces greater myocardial dysfunction than with either disease alone and is associated with a significant mortality.


1989 ◽  
Vol 256 (5) ◽  
pp. H1274-H1281 ◽  
Author(s):  
D. N. Darlington ◽  
K. Kaship ◽  
L. C. Keil ◽  
M. F. Dallman

To determine under resting, unstressed conditions the circulating glucocorticoid concentrations that best maintain sensitivity of the vascular smooth muscle and baroreceptor responses to vasoactive agents, rats with vascular cannulas were sham-adrenalectomized (sham) or adrenalectomized (ADRX) and provided with four levels of corticosterone replacement (approximately 100 mg fused pellets of corticosterone: cholesterol 0, 20, 40, and 80% implanted subcutaneously at the time of adrenal surgery). Changes in vascular and baroreflex responses were determined after intravenous injection of varying doses of phenylephrine and nitroglycerin with measurement of arterial blood pressure and heart rate in the conscious, chronically cannulated rats. Vascular sensitivity was decreased, and resting arterial blood pressure tended to be decreased in the adrenalectomized rats; both were restored to normal with levels of corticosterone (40%), which also maintained body weight gain, thymus weight, and plasma corticosteroid binding globulin concentrations at normal values. The baroreflex curve generated from the sham group was different from the curves generated from the ADRX+0, 20, and 40% groups, but not different from that of the ADRX+80% group, suggesting that the baroreflex is maintained by higher levels of corticosterone than are necessary for the maintenance of the other variables. These data demonstrate that physiological levels of corticosterone (40% pellet) restore vascular responsiveness, body weight, thymus weight, and transcortin levels to normal in ADRX rats, whereas higher levels (80% pellet) are necessary for restoration of the baroreflex.


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