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 ◽  
...  

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.

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Saheem Ahmad ◽  
Mohd. Sajid Khan ◽  
Sultan Alouffi ◽  
Saif Khan ◽  
Mahvish Khan ◽  
...  

Proteins undergo glycation resulting in the generation of advanced glycation end products (AGEs) that play a central role in the onset and advancement of diabetes-associated secondary complications. Aminoguanidine (AG) acts as an antiglycating agent by inhibiting AGE generation by blocking reactive carbonyl species (RCS) like, methylglyoxal (MGO). Previous studies on antiglycating behavior of AG gave promising results in the treatment of diabetes-associated microvascular complications, but it was discontinued as it was found to be toxic at high concentrations (>10 mmol/L). The current article aims at glycation inhibition by conjugating gold nanoparticles (Gnp) with less concentration of AG (0.5-1.0 mmol/L). The HPLC results showed that AG-Gnp fairly hampers the formation of glycation adducts. Moreover, the in vivo studies revealed AG-Gnp mediated inhibition in the production of total-AGEs and - N ε -(carboxymethyl)lysine (CML) in the diabetic rat model. This inhibition was found to be directly correlated with the antioxidant parameters, blood glucose, insulin, and glycosylated hemoglobin levels. Furthermore, the histopathology of AG-Gnp-treated rats showed good recovery in the damaged pancreatic tissue as compared to diabetic rats. We propose that this approach might increase the efficacy of AG at relatively low concentrations to avoid toxicity and might facilitate to overcome the hazardous actions of antiglycating drugs.


2013 ◽  
Vol 220 (3) ◽  
pp. 291-304 ◽  
Author(s):  
Mohamed Lotfy ◽  
Jaipaul Singh ◽  
Hameed Rashed ◽  
Saeed Tariq ◽  
Erika Zilahi ◽  
...  

Glucagon-like peptide 1 (GLP1) agonists are promising therapeutic agents in the treatment of diabetes mellitus. This study examines the mechanism of the protective effects of exenatide in experimental diabetes, employing four groups of ten rats each, in which two groups were streptozotocin-induced diabetic and two were control groups. One control and one diabetic group were treated with exenatide (1 μg/kg body weight (BW)) for 10 weeks. Blood plasma was taken for biochemical analyses while pancreatic tissue was taken for immunofluorescence and immunoelectron microscopy studies and real-time PCR to examine the expression of genes. The results show that exenatide improved BW gain and reduced blood glucose in diabetic rats compared with controls. Similarly, exenatide enhanced insulin release from the pancreatic fragments and improved liver and kidney functions and lipid profile in diabetic rats compared with controls. Exenatide not only induced significant increases in serum insulin level but also elevated the number of insulin-, GLP1- and exenatide-positive cells compared with untreated controls. Exenatide also elevated the number of catalase- and glutathione reductase-positive cells in diabetic rat pancreas compared with controls. Exenatide caused significant elevation in the expressions of pancreatic duodenal homeobox-1, heat shock protein-70, glutathione peroxidase, insulin receptor and GLP1 receptor genes in the pancreas of both control and diabetic rats compared with untreated animals. The results have demonstrated that exenatide can exert its beneficial and protective effects by elevating the levels of endogenous antioxidants and genes responsible for the survival, regeneration and proliferation of pancreatic β-cell.


2016 ◽  
Vol 8 (4) ◽  
pp. 414-421 ◽  
Author(s):  
Rasheed Bolaji IBRAHIM ◽  
Jubril Olayinka AKOLADE ◽  
Raliat Abimbola ALADODO ◽  
Omoaruemike Ebele OKEREKE ◽  
Sarah Abimbola AKANDE

The antidiabetic potentials of Heliotropium indicum L. leaf aqueous (HILA) extract used for the management of diabetes by Traditional Medicinal Practitioners (TMPs) in Nigeria was assessed. Alloxan (ALX)-induced hyperglycaemic rats were orally administered with known folkloric dosage of 30 and 75 mg/kg b. wt. of HILA extract, once a day, for 14 days. Fasting blood glucose (FBG) levels were monitored and pancreatic histology was examined. Net hepatic glycogen (GLY) concentration and lipid profiles were also determined. Prior to treatment, ALX-induced hyperglycaemia (>250 mg/dL) was established in rats. Oral administration of 30 and 75 mg/kg b. wt. HILA extract to diabetic rats for 14 days caused significant reduction in FBG to baseline values observed in non-diabetic conditions. Treatment with HILA extract also showed improvement in lipid abnormalities observed in hyperglycaemic condition, levels of triglyceride, total cholesterol and LDL-cholesterol were significantly reduced and HDL-cholesterol increased resulting in improved artherogenic index. Hepatic GLY concentration was significantly increased in diabetic rat treated with the extract. Histological examinations showed degenerated and sparse pancreatic islets β-cells in non-treated diabetic rat, whereas microscopy of treated rats showed mild to normal architecture with enriched β-cells. Preliminary phytochemical profiling of the extract revealed the presence of alkaloids (2.54 mg/g), saponins (0.28 mg/g), phenols (0.04 mg/g) and anthraquinones (0.01 mg/g). Results from this study revealed that the aqueous leaf extract of H. indicum possesses not only antihyperglycaemic, but also antidyslipidemic activities, that may prove to be of clinical importance in the management of diabetes and associated secondary complications.


2019 ◽  
Vol 15 (6) ◽  
pp. 634-647
Author(s):  
Sahar M. Abou-Seri ◽  
AlShaimaa M. Taha ◽  
Mona A. Mohamed ◽  
Nour M. Abdelkader

Background:Sulphonylureas are the oldest and commonly used to treat diabetic patients, but its efficacy declines by time. It was reported that quinazoline nucleus exhibits a potent hypoglycemic effect in diabetic animal models.Objective:The current study aimed to synthesize new quinazoline-sulfonylurea conjugates and evaluate their hypoglycemic effects in alloxan-induced diabetic rats.Methods:The conjugates were synthesized by bioisosteric replacement of 5-chloro-2-methoxybenzamide moiety in glibenclamide or 1,3-dioxo-3,4-dihydroisoquinoline moiety in gliquidone with 6,7-dimethoxy-4-oxoquinazoline moiety (compounds 4a-4d, 9b-9c and 10b-10d). Diabetes was induced in rats by a single i.p. administration of alloxan, followed by treatment with the synthesized conjugates (5mg/kg Body weight).Results:All conjugates showed hypoglycemic effects with different efficacy indicated by the reduction in blood glucose and elevation of insulin levels. Moreover, these conjugates up-regulated the expression of pancreatic glucose transporter 2, muscle glucose transporter 4, and insulin receptor substrate-1 genes, compared to the diabetic group. A normal pancreatic tissue pattern was noticed in diabetic rats treated with compounds 9b, 9c, and 10c.Conclusion:Conjugation of sulfonylurea with quinazoline (especially 9b, 9c, 10c) possessed a significant hypoglycemic effect through improving blood insulin level and insulin action and consequently increased the glucose uptake by the skeletal muscles.


1958 ◽  
Vol 192 (3) ◽  
pp. 514-516 ◽  
Author(s):  
W. L. Henry ◽  
John H. Kim ◽  
Alice S. Hall

The liver glycogenating action of Orinase was studied in normal, adrenalectomized and alloxan diabetic rats. The adrenalectomized rats were studied in three groups, salt maintained, cortisone maintained and cortisone plus adrenaline maintained. The alloxan diabetic rats were studied in two groups, protamine zinc insulin (P.Z.I.) maintained and uncontrolled. Of the adrenalectomized rats only those maintained on cortisone plus adrenaline responded to Orinase administration with increased liver glycogen. The alloxan diabetic animal maintained on P.Z.I. presented increased liver glycogen after Orinase administration but the untreated alloxan diabetic rat did not. This series of experiments indicated that the liver glycogenating effect seen during Orinase administration requires the participation of adrenomedullary, adrenocortical and beta cell hormones.


2018 ◽  
Vol 21 (04) ◽  
pp. 717-722
Author(s):  
Muhammad Sajid Khan ◽  
Aneela Qureshi ◽  
Shuja Anwar Kazi ◽  
Amin Fahim ◽  
Husan Bano ◽  
...  

Objective: To evaluate the anti diabetic effect of cinnamon extract in alloxaninduced diabetic animal model (albino rats) in comparison with oral hypoglycemic drugs. StudyDesign: An Experimental study. Place of Study: Al Tibri Medical College, Isra University, KarachiCampus. Duration of Study: December 2012 to December 2013. Materials and Methods: Total60 Albino rats of both genders were divided into 6 groups consisting of 10 rats in each group.Each group of animals was further divided into two sub groups containing 5 rats in each groupResults: The results obtained from the data indicated that there is significant reduction in bloodglucose level rats treated with low dose of cinnamon extract. The animals of low dose cinnamonextract (200mg/kg. bw) when compared with other groups; there is a reduction in the bloodglucose level in alloxan induced diabetic rats. Also tolbutamide and acarbose treated groupsshowed better antidiabetic effects as compared with cinnamon extract treated groups (pvalue<0.007 and p value<0.012 respectively), but cinnamon extract treated group showedsynergetic effects when it was given in combination with tolbutamide or acarbose havingsignificant p value<0.001 and p value<0.011 respectively. Conclusions: Tolbutamide andAcarbose showed better anti diabetic effect in comparison with cinnamon extract treated groupswhen used individually. This effect was enhanced when cinnamon was used in combination witheither tolbutamide or acarbose.


1982 ◽  
Vol 60 (10) ◽  
pp. 1251-1256 ◽  
Author(s):  
Victor Chen ◽  
C. David Ianuzzo

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.


2020 ◽  
Vol 11 (4) ◽  
pp. 5067-5070
Author(s):  
Pang Jyh Chayng ◽  
Nurul Ain ◽  
Kaswandi Md Ambia ◽  
Rahim Md Noah

The purpose of this project is to study the anti-diabetic effect of on a diabetic rat model. A total of Twenty male Sprague rats were used and it randomly distributed into four groups which are Group I: , Group II: negative control, Group III: and Group IV: and . In diabetic model were induced with via injection at the dosage of 65mg/kg. and FBG (Fasting Blood Glucose) level of diabetic rats were assessed every three days. Blood was collected via cardiac puncture at day 21 after the induction of treatment. Insulin level of the rats was assessed with the Mercodia Rat Insulin ELISA kit. FBG level of group I (12.16 ±3.96, p&lt;0.05) and group IV (11.34 ±3.67, p&lt;0.05) were significantly decreased. Meanwhile, the for all rats did not show any significant increase. However, the insulin level was escalated in group IV (0.74+0.25, p&lt;0.05) significantly. The present study shows that the and the combination of and lowered blood glucose level and enhanced insulin secretion.


2014 ◽  
Vol 92 (4) ◽  
pp. 338-349 ◽  
Author(s):  
Kiranj K. Chaudagar ◽  
Anita A. Mehta

Atorvastatin, a lipid lowering agent, possesses various pleiotropic vasculoprotective effects, but its role in coronary angiogenesis is still controversial. Our objective was to study the effects of atorvastatin on the angiogenic responsiveness of coronary endothelial cells (cEC) from normal and diabetic rats. Male Wistar rats were distributed among 9 groups; (i) normal rats, (ii) 30 day diabetic rats, (iii) 60 day diabetic rats, (iv) normal rats administered a low dose of atorvastatin (1 mg/kg body mass, per oral (p.o.), for 15 days); (v) 30 day diabetic rats administered a low dose of atorvastatin; (vi) 60 day diabetic rats administered a low dose of atorvastatin; (vii) normal rats administered a high dose of atorvastatin (5 mg/kg, p.o., for 15 days); (viii) 30 day diabetic rats administered a high dose of atorvastatin; (ix) 60 day diabetic rats administered a high dose of atorvastatin. Each group was further divided into 2 subgroups, (i) sham ischemia–reperfusion and (ii) rats hearts that underwent ischemia–reperfusion. Angiogenic responsiveness the and nitric oxide (NO) releasing properties of the subgroups of cECs were studied using a chorioallantoic membrane assay and the Griess method, respectively. Atorvastatin treatment significantly increased VEGF-induced angiogenic responsiveness and the NO-releasing properties of cECs from all of the subgroups, compared with their respective non-treated subgroups except for the late-phase diabetic rat hearts that underwent ischemia–reperfusion, and the high dose of atorvastatin treatment groups. These effects of atorvastatin were significantly inhibited by pretreatment of cECs with l-NAME, wortmannin, and chelerythrine. Thus, treatment with a low dose of atorvastatin improves the angiogenic responsiveness of the cECs from normal and diabetic rats, in the presence of VEGF, via activation of eNOS–NO release.


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