Attenuation of streptozotocin-induced diabetes in rats by pretreatment with chloroquine

1989 ◽  
Vol 76 (2) ◽  
pp. 137-141 ◽  
Author(s):  
Kojo A. Asamoah ◽  
Brian L. Furman ◽  
Donald A. Robb
Keyword(s):  
Plasma Protein ◽  
Plasma Glucose ◽  
Chronic Administration ◽  
Glycated Haemoglobin ◽  
Diabetic Rats ◽  
Immunoreactive Insulin ◽  
Protein Levels ◽  
Glucose Homoeostasis ◽  
Chloroquine Treatment ◽  
Plasma Immunoreactive Insulin

1. The effect of chronic administration of chloroquine on glucose homoeostasis was investigated in normal and diabetic rats by determining fasting plasma glucose, glycated plasma protein, plasma immunoreactive insulin, plasma protein and glycated haemoglobin. Animal weights, as well as the survival of the diabetic animals without insulin therapy, were also observed. 2. Apart from an elevation in the plasma immunoreactive insulin levels (4.1 ± 0.6 vs 2.1 ± 0.4 μg/l, P < 0.025), there were no significant differences among the other parameters compared with age-matched controls up to week 12 for the normal rats on chloroquine treatment. After 20 weeks of treatment, however, plasma glucose (7.2 ± 0.1 vs 8.4 ± 0.2 mmol/l, P < 0.005) and glycated haemoglobin (2.9 ± 0.1 vs 3.3 ± 0.1%, P < 0.01) levels were lower in the treated animals. Diabetic rats treated with chloroquine for 12 weeks before the onset of diabetes showed significantly higher plasma insulin and protein levels than control diabetic animals, while plasma glucose (17.7 ± 2.5 vs 29.4 ± 1.7 mmol/l, P < 0.005), glycated plasma protein and glycated haemoglobin (6.6 ± 0.4 vs 7.8 ± 0.4%, P < 0.05) levels were lower. 3. It is concluded that after a prolonged administration of chloroquine there is a hypoglycaemic effect in normal animals, and pretreatment with the drug ameliorates diabetes induced subsequently.

Comparison of the glucose-lowering properties of vanadyl sulfate and bis(maltolato)oxovanadium(IV) following acute and chronic administration

1995 ◽  
Vol 73 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Violet G. Yuen ◽  
J. H. McNeill ◽  
C. Orvig
Keyword(s):  
Oral Administration ◽  
Dose Response ◽  
Plasma Glucose ◽  
Intraperitoneal Injection ◽  
Chronic Administration ◽  
Diabetic Rats ◽  
Vanadyl Sulfate ◽  
Oral Gavage ◽  
Glucose Lowering ◽  
Glucose Levels

Numerous studies, both in vitro and in vivo, have demonstrated the insulin-mimetic properties of vanadium. Chronic oral administration of inorganic and organic compounds of both vanadium(IV) and vanadium(V) reduced plasma glucose levels and restored plasma lipid levels in streptozotocin-diabetic rats. We investigated the acute effects of both vanadyl sulfate and bis(maltolato)oxovanadium(IV) (BMOV), an organic vanadium compound, on plasma glucose levels by several routes of administration. Previous studies have shown that chronic administration of vanadyl sulfate has resulted in a sustained euglycemia following withdrawal of the drug. This effect was not observed following the chronic administration of BMOV; therefore, we investigated the effect of increasing the concentration of BMOV on the production of a sustained euglycemic response. An acute plasma glucose lowering effect was obtained with both vanadyl sulfate and BMOV when administered as a single dose by either oral gavage or intraperitoneal injection. In those animals that responded to vanadium treatment, plasma glucose levels were within the normal range within 2 to 6 h when given by i.p. injection or within 4 to 8 h when given by oral gavage. BMOV-treated rats that responded to treatment maintained the euglycemic effect for extended periods, ranging from 1 to 14 weeks following administration. However, vanadyl sulfate treated rats reverted to hyperglycemia within 12 to 24 h, depending on the route of administration. Intravenous administration of BMOV was effective in lowering plasma glucose levels only when administered by continuous infusion. An oral dose – response curve showed that BMOV was 2 to 3 times as potent as vanadyl sulfate. This difference in potency was observed with both oral and intraperitoneal administration, which suggests that the increase in potency with BMOV cannot be totally attributed to increased gastrointestinal absorption. Organic chelation of vanadium may facilitate uptake into vanadium-sensitive tissues. Chronic oral administration of higher concentrations of BMOV did not result in a sustained reduction in plasma glucose following withdrawal of the drug. All diabetic rats eventually responded to increased concentrations of BMOV with a restoration of plasma glucose levels to normal values; however, reversion to the hyperglycemic state occurred within 2 days of withdrawal of treatment. Chronic oral administration of BMOV did not produce a sustained euglycemic effect following withdrawal, but acute administrations of the compound by either oral gavage or intraperitoneal injection did produce a long-term reduction in plasma glucose levels. Rats treated chronically with vanadyl sulfate remained euglycemic even after the drug was withdrawn. However, acute treatment produced only a transient euglycemia.Key words: streptozotocin diabetic, acute, bis(maltolato)oxovanadium(IV), vanadyl sulfate, dose response.

Dosage effect of streptozotocin on rat tissue enzyme activities and glycogen concentration

1982 ◽  
Vol 60 (10) ◽  
pp. 1251-1256 ◽  
Author(s):  
Victor Chen ◽  
C. David Ianuzzo
Keyword(s):  
Body Weight ◽  
Enzyme Activities ◽  
Gastrocnemius Muscle ◽  
Glycogen Content ◽  
Normal Liver ◽  
Diabetic Rats ◽  
Immunoreactive Insulin ◽  
Glycogen Concentration ◽  
Plasma Immunoreactive Insulin ◽  
Rat Tissue

The effect of different dosages of streptozotocin (STZ) on selected rat tissue enzyme activities and glycogen concentration were investigated. The rats were administered STZ intravenously at 60 (STZ-60), 80 (STZ-80), 100 (STZ-100), and 150 (STZ-150) mg/kg body weight. They were used 3 weeks postinjection. Mortality prior to kill occurred only in the STZ-100 and STZ-150 rats. All diabetic rats showed reduced growth rate, hyperglycemia, hypoinsulinemia, and hyperlipemia. Phoshofructokinase (PFK) and succinate dehydrogenase (SDH) activities were significantly reduced in the red gastrocnemius muscle of all diabetic rats, and in the white gastrocnemius and soleus of STZ-100 and STZ-150 groups. PFK activity in the heart remained unaltered, but SDH activity was below normal. Liver SDH activity was not affected by insulin deficiency. Glycogen content was markedly increased in the heart and decreased in the liver of all diabetic rats. Glycogen content in the skeletal muscle was similar to the controls, except for the lower values in the soleus of STZ-100 and STZ-150 rats. When STZ-80 and STZ-150 rats were given insulin therapy, the STZ-80 rats showed a greater response to the treatment. Despite similar levels of plasma immunoreactive insulin among all groups of diabetic rats, the STZ-100 and STZ-150 rats had higher mortality, greater loss in body weight, and alterations in enzyme activities and glycogen content in the tissues studied.

scholarly journals Mediation of Endogenous β-Endorphin by Tetrandrine to Lower Plasma Glucose in Streptozotocin-Induced Diabetic Rats

2004 ◽  
Vol 1 (2) ◽  
pp. 193-201 ◽  
Author(s):  
Jen-Hao Hsu ◽  
Yang-Chang Wu ◽  
Shorong-Shii Liou ◽  
I-Min Liu ◽  
Lee-Wen Huang ◽  
...  
Keyword(s):  
Adrenal Medulla ◽  
Soleus Muscle ◽  
Plasma Glucose ◽  
Nicotinic Receptors ◽  
Diabetic Rats ◽  
Lower Plasma ◽  
Glucose Lowering ◽  
Protein Levels ◽  
Lower Plasma Glucose ◽  
Glucose Lowering Effect

The role of β-endorphin in the plasma glucose-lowering action of tetrandrine in streptozotocin-induced diabetic rats (STZ-diabetic rats) was investigated. The plasma glucose concentration was assessed by the glucose oxidase method. The enzyme-linked immunosorbent assay was used to determine the plasma level of β-endorphin-like immunoreactivity (BER). The mRNA levels of glucose transporter subtype 4 (GLUT4) in soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver of STZ-diabetic rats were detected by Northern blotting analysis. The expressed protein of GLUT4 or PEPCK was characterized by Western blotting analysis. Tetrandrine dose-dependently increased plasma BER in a manner parallel to the decrease of plasma glucose in STZ-diabetic rats. Moreover, the plasma glucose-lowering effect of tetrandrine was inhibited by naloxone and naloxonazine at doses sufficient to block opioid μ-receptors. Further, tetrandrine failed to produce plasma glucose-lowering action in opioid μ-receptor knockout diabetic mice. Bilateral adrenalectomy eliminated the plasma glucose-lowering effect and plasma BER-elevating effect of tetrandrine in STZ-diabetic rats. Both effects were abolished by treatment with hexamethonium or pentolinium at doses sufficient to block nicotinic receptors. Tetrandrine enhanced BER release directly from the isolated adrenal medulla of STZ-diabetic rats and this action was abolished by the blockade of nicotinic receptors. Repeated intravenous administration of tetrandrine (1.0 mg/kg) to STZ-diabetic rats for 3 days resulted in an increase in the mRNA and protein levels of the GLUT4 in soleus muscle, in addition to the lowering of plasma glucose. Similar treatment with tetrandrine reversed the elevated mRNA and protein levels of PEPCK in the liver of STZ-diabetic rats. The obtained results suggest that tetrandrine may induce the activation of nicotinic receptors in adrenal medulla to enhance the secretion of β-endorphin, which could stimulate opioid μ-receptors to increase glucose utilization or/and reduce hepatic gluconeogenesis to lower plasma glucose levels in STZ-diabetic rats.

Glucocorticoid effects on respiration and metabolism by rat liver homogenates

1962 ◽  
Vol 202 (2) ◽  
pp. 343-346 ◽  
Author(s):  
Dennis D. Goetsch ◽  
L. E. McDonald
Keyword(s):  
Lactic Acid ◽  
Oxygen Uptake ◽  
Rat Liver ◽  
Inorganic Phosphate ◽  
Chronic Administration ◽  
Glucocorticoid Treatment ◽  
Carbohydrate Utilization ◽  
Protein Levels ◽  
Liver Homogenates ◽  
And Control

The effects of glucocorticoid administration on oxygen uptake, glucose and glycogen disappearance, lactic acid formation, and inorganic phosphate and protein levels in rat liver homogenates have been studied. A single injection of hydrocortisone, prednisolone, or 9 α-fluoroprednisolone 5 hr before sacrifice resulted in a highly significant increase in oxygen uptake by rat liver homogenates, whereas chronic administration of prednisolone daily for 7 days caused a marked inhibition in homogenate respiration. Glycolytic rate did not appear to be affected by single injections since endogenous carbohydrate utilization was similar in liver homogenates prepared from control and treated animals. Incubation of liver homogenates under aerobic conditions disclosed that inorganic phosphate levels were decreased in homogenates from corticoid-treated rats, whereas these levels were similar in treated and control liver homogenates incubated under nitrogen. Under anaerobic conditions, liver homogenates from treated rats accumulated lactic acid more rapidly than untreated liver homogenates. Glucocorticoid treatment did not appear to affect protein disappearance since no differences between protein levels in treated and untreated rat liver homogenates were detected following incubation.

NEONATAL ISLET CELL TRANSPLANTATION IN THE DIABETIC RAT: EFFECT ON HEPATIC ENZYME ACTIVITY AND GLUCOSE HOMEOSTASIS

1977 ◽  
Vol 74 (2) ◽  
pp. 231-241 ◽  
Author(s):  
YVONNE MANGNALL ◽  
ANNE SMYTHE ◽  
D. N. SLATER ◽  
GILLIAN R. MILNER ◽  
R. D. G. MILNER ◽  
...  
Keyword(s):  
Diabetic Animal ◽  
Pancreatic Tissue ◽  
Diabetic Rats ◽  
Neonatal Rat ◽  
Diabetic Rat ◽  
Immunoreactive Insulin ◽  
Hepatic Glycogen ◽  
Islet Cell Transplantation ◽  
Glycogen Concentration ◽  
Serum Immunoreactive Insulin

Intraperitoneal transplantation of collagenase-digested, isogeneic, neonatal rat pancreatic tissue successfully reversed streptozotocin-induced diabetes in 77% of recipients. The low serum immunoreactive insulin, hyperglycaemia, glycosuria and weight loss, characteristic of the diabetic animal, were corrected and the reduced activities of hepatic glucokinase and pyruvate kinase, and the low glycogen concentration of the liver of diabetic rats were restored to normal. Forty-three per cent of the successfully transplanted rats became normoglycaemic within 1 month of transplantation whereas 57% took from 1 to 6 months to achieve normoglycaemia and displayed a mild glucose intolerance when subjected to a glucose load. The rats which had not become normoglycaemic 6 months after transplantation showed some amelioration of the diabetic state, as shown by increased serum immunoreactive insulin and hepatic glycogen concentration and a slow weight gain compared with diabetic controls.

Comparative evaluation of probiotics effects on plasma glucose, lipid, and insulin levels in streptozotocin-induced diabetic rats

2017 ◽  
Vol 33 (7) ◽  
pp. e2912 ◽  
Author(s):  
Faeghe Memarrast ◽  
Soudeh Ghafouri-Fard ◽  
Sedighe Kolivand ◽  
Saeedeh Jafary-Nodooshan ◽  
Nadia Neyazi ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Comparative Evaluation ◽  
Diabetic Rats ◽  
Insulin Levels

scholarly journals Short-Term Feeding of Fibre-Enriched Biscuits: Protective Effect against Hepatotoxicity in Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Ochuko L. Erukainure ◽  
Osaretin A. T. Ebuehi ◽  
Folasade O. Adeboyejo ◽  
Olufunmilola O. Oladunmoye ◽  
Muhammad Aliyu ◽  
...  
Keyword(s):  
Protective Effect ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hepatic Function ◽  
Treated Group ◽  
Albumin Level ◽  
Diabetic Rats ◽  
Protein Levels ◽  
Significant Difference ◽  
Alloxan Monohydrate

The effects of fibre-enriched biscuit on biomarkers associated with hepatotoxicity in diabetic rats were investigated. Diabetes was induced by single intraperitoneal injection of alloxan monohydrate. Treatment lasted for 14 days after which the rats were sacrificed by cervical dislocation. Blood serum was analyzed to determine hepatic function enzymes. The liver was also analyzed to determine hepatic lipid profile and antioxidant enzymes. Induction of diabetes led to elevated levels of ALP, AST, and ALT. These were, however, significantly (p<0.05) reduced in the fibre-enriched biscuit fed (treated) group. There was no significant difference in the serum bilirubin and total protein levels of the studied groups. Reduced albumin level was observed in the diabetic group; this was further lowered on feeding with fibre-enriched biscuits. Induction of diabetes led to increased hepatic level of cholesterol, triglyceride (TG), low density lipoprotein (LDL), and lipid peroxidation and decreased activities of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) and HDL level. These were significantly (p<0.05) reversed on feeding with fibre-enriched biscuit. This study portrays the protective effect of fibre-enriched biscuit on increased oxidative stress and hyperlipidemia in hepatic tissues of alloxan-induced diabetic rats.

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