scholarly journals Improving the Reliability and Utility of Streptozotocin-Induced Rat Diabetic Model

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Yanlin Wang-Fischer ◽  
Tina Garyantes
Keyword(s):  
Side Effects ◽  
Sodium Channel ◽  
Pancreatic Islets ◽  
Pancreatic Tissue ◽  
Diabetic Rats ◽  
Partial Recovery ◽  
Sprague Dawley ◽  
Area Reduction ◽  
Diabetic Model ◽  
Pancreatic Toxicity

The Streptozotocin- (STZ-) induced diabetic model is widely used; however, unexplained acute toxicity has given the model an unreliable reputation. To improve the reliability and utility of this model, we characterize the age dependence of STZ toxicity and introduce novel endpoints to assess diabetic complications and reveal possible mechanisms for diabetic development. Diabetes was induced by STZ injection into male, 6 to 23 weeks old, Sprague-Dawley rats. Their metabolic (glucose, lipids, and hormones), inflammatory (cytokines), histologic and behavioral endpoints were observed for 1.2 years. Analgesic compounds were assessed for efficacy treating neuropathy. Acute mortality, within a week of STZ injection (50–65 mg/kg i.v.), was inversely correlated to animal age. Only 3% of rats, age 6–11 weeks, died in the week following STZ injection, whereas 83% of rats 12 to 17 weeks old and 91% of rats 18 weeks or older died in the same week. Partial model recovery (normalized insulin, glucose and food/water intake) was observed starting at week 36; however, pain scores, kidney enlargement, and cataract formation continued to show progression consistent with the diabetic state. Unique noninvasive observational measurements, such as haircoat quality and diarrhea scores, served as useful endpoints for this model. The increased plasma cytokines (such as TNF-α, IL-4, and IL-6) and inflammatory cell infiltration into the pancreatic islets are strong evidence of inflammation in the STZ-induced diabetic model. Pancreatic tissue staining revealed total islet area reduction and confirmed STZ-specific pancreatic toxicity; however, the β-cell density per area in pancreatic islets and insulin levels statistically increased over time in the diabetic rats, suggesting a mechanism for partial recovery of diabetic symptoms. Voltage-gated sodium channel (NaV1.7 specific, peripherally restricted) blocker, CC4148, inhibited neuropathy without side effects as compared to a nonspecific sodium channel inhibitor, Mexiletine, or GABA analog, Pregabalin, which inhibited neuropathy with side effects.

scholarly journals Pancreatic Islets Accumulate Cadmium in a Rodent Model of Cadmium-Induced Hyperglycemia

2020 ◽  
Vol 22 (1) ◽  
pp. 360
Author(s):  
Ryan Fitzgerald ◽  
Andrew Olsen ◽  
Jessica Nguyen ◽  
Winifred Wong ◽  
Malek El Muayed ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Fasting Blood Glucose ◽  
Pancreatic Tissue ◽  
Experimental Models ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Low Glucose

Cadmium (Cd) is an anthropogenic as well as a naturally occurring toxicant associated with prediabetes and T2DM in humans and experimental models of Cd exposure. However, relatively few studies have examined the mechanism(s) of Cd-induced hyperglycemia. The purpose of this study was to examine the role of pancreatic islets in Cd-induced hyperglycemia. Male Sprague–Dawley rats were given daily subcutaneous doses of Cd at 0.6 mg/kg over 12 weeks. There was a resulting time-dependent increase in fasting blood glucose and altered insulin release in vitro. Islets isolated from control (saline-treated) and Cd-treated animals were incubated in low (0.5 mg/mL) or high (3 mg/mL) glucose conditions. Islets from 12 week Cd-treated animals had significantly less glucose-stimulated insulin release compared to islets from saline-treated control animals. The actual Cd content of isolated islets was 5 fold higher than the whole pancreas (endocrine + exocrine) and roughly 70% of that present in the renal cortex. Interestingly, islets isolated from Cd-treated animals and incubated in high glucose conditions contained significantly less Cd and zinc than those incubated in low glucose. These results show that within whole pancreatic tissue, Cd selectively accumulates in pancreatic islets and causes altered islet function that likely contributes to dysglycemia.

scholarly journals Antidiabetic Effect of Katakakhadiradi kashayam by Improving the Insulin Expression and Glucose Metabolising Enzyme

2021 ◽  
pp. 1-8
Author(s):  
Angelie Jessica Subbiah ◽  
M. Kavimani ◽  
Mukilan Ramadoss ◽  
Mudiganti Ram Krishna Rao ◽  
K. Prabhu
Keyword(s):  
Side Effects ◽  
Wistar Rats ◽  
Pancreatic Tissue ◽  
Diabetic Rats ◽  
Β Cells ◽  
Metabolizing Enzymes ◽  
Antihyperglycemic Activity ◽  
Antidiabetic Effect ◽  
Pathological Conditions ◽  
Insulin Expression

Many plants provide a rich source of bioactive chemicals, which are free from undesirable side effects and possess powerful pharmacological actions. The present study was carried out to find the antidiabetic effect of   Katakakhadiradi kashayam (KKK) by improving the insulin expression and regulating properly the glucose metabolising enzymes. The diabetes was induced in combination with streptozotocin and nicotinamide injection to Wistar rats. Diabetic rats were treated with   Katakakhadiradi kashayam orally at doses of 100, 200 and 300 mg/kg/bw for 28 days, and the obtained results of parameters were compared with glibenclamide. The antidiabetic effect of Kashayam was measured by the expression of insulin by immunohistochemistry and restoring the normal clinical values of glucose metabolizing enzymes. The present study specified that hyperglycemia leads to pathological conditions in pancreatic tissue with decreased expression of insulin in β-cells whereas the   Katakakhadiradi kashayam normalised the production of insulin. The study found that the antihyperglycemic activity of   Katakakhadiradi kashayam L. is mainly due to their ability to restore the function of pancreatic tissues by causing an increase in insulin output and maintaining the glucose metabolising enzymes.

scholarly journals Resveratrol Improves Cognitive Impairment by Regulating Apoptosis and Synaptic Plasticity in Streptozotocin-Induced Diabetic Rats

2016 ◽  
Vol 40 (6) ◽  
pp. 1670-1677 ◽  
Author(s):  
Zhiyan Tian ◽  
Jinhua Wang ◽  
Ming Xu ◽  
Yan Wang ◽  
Miao Zhang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Protein Expression ◽  
Cognitive Decline ◽  
Caspase 3 ◽  
Diabetic Rats ◽  
Morris Water Maze Test ◽  
Sprague Dawley ◽  
Resveratrol Treatment ◽  
Sprague Dawley Rats ◽  
Diabetic Model

Aims: To investigate the effects of resveratrol on cognitive impairment in streptozotocin (STZ)-induced diabetic rats and to explore the mechanisms of that phenomenon. Methods: Sixty healthy male Sprague Dawley rats were randomly divided into four groups: normal control group (Con group, n = 15), Res group (normal Sprague Dawley rats treated with resveratrol, n = 15), diabetes mellitus group (DM group, n = 15) and DM + Res group (diabetic rats treat with resveratrol, n = 15). Streptozotocin (STZ) was injected intraperitoneally to establish the diabetic model. One week after diabetic model induction, the animals in the Res group and the DM + Res group received resveratrol intraperitoneally once a day for consecutive 4 weeks. The Morris water maze test was applied to assess the effect of resveratrol on learning and memory. To explore the mechanisms of resveratrol on cognition, we detected the protein expression levels of Caspase-3, Bcl-2, Bax, NMDAR1 (N-Methyl-d-Aspartate receptor) and BDNF (Brain Derived Neurotrophic Factor) via western blotting analysis. Results: Resveratrol has no obvious effect on normal SD rats. Compared to Con group, cognitive ability was significantly impaired with increased expression of Caspase-3, Bax and down-regulation of Bcl-2, NMDAR1 and BDNF in diabetic rats. By contrast, resveratrol treatment improved the cognitive decline. Evidently, resveratrol treatment reversed diabetes-induced changes of protein expression. Conclusions: Resveratrol significantly ameliorates cognitive decline in STZ-induced diabetic model rats. The potential mechanism underlying the protective effect could be attributed to the inhibition of hippocampal apoptosis through the Bcl-2, Bax and Caspase-3 signaling pathways and improvement of synaptic dysfunction. BDNF may also play an indispensable role in this mechanism.

Intraportal transplantation of pancreatic islets into livers of diabetic rats. Reinnervation of islets and regulation of insulin secretion by the hepatic sympathetic nerves

Diabetes ◽  
1994 ◽  
Vol 43 (11) ◽  
pp. 1345-1352 ◽  
Author(s):  
A. Gardemann ◽  
K. Jungermann ◽  
V. Grosse ◽  
L. Cossel ◽  
F. Wohlrab ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Sympathetic Nerves ◽  
Diabetic Rats

scholarly journals Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?

2021 ◽  
Author(s):  
Tongtong Zhao ◽  
Kai Zhang ◽  
Yelei Zhang ◽  
Yating Yang ◽  
Xiaoshuai Ning ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Side Effects ◽  
Proinflammatory Cytokines ◽  
Peripheral Blood ◽  
Animal Experiments ◽  
Pancreatic Tissue ◽  
Mouse Serum ◽  
Healthy Controls ◽  
Immunological Mechanisms ◽  
Tnf Α

Abstract Rationale and objective Clozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders. Methods We measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophrenia patients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue. Results Following clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-β levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1β, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients’ BMI, blood glucose, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1β and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α. Conclusion Findings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.

scholarly journals Cigarette smoke inhalation aggravates diabetic kidney injury in rats

2019 ◽  
Vol 8 (6) ◽  
pp. 964-971 ◽  
Author(s):  
Songling Jiang ◽  
Do Van Quan ◽  
Jae Hyuck Sung ◽  
Moo-Yeol Lee ◽  
Hunjoo Ha
Keyword(s):  
Kidney Disease ◽  
Cigarette Smoke ◽  
Density Lipoprotein ◽  
Kidney Injury ◽  
Diabetic Rats ◽  
Smoke Inhalation ◽  
Lipoprotein Cholesterol ◽  
Sprague Dawley ◽  
Experimental Conditions ◽  
Diabetic Kidney

Abstract Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Epidemiological studies have demonstrated that cigarette smoke or nicotine is a risk factor for the progression of chronic kidney injury. The present study analyzed the kidney toxicity of cigarette smoke in experimental rats with DKD. Experimental diabetes was induced in 7-week-old Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin (60 mg kg−1). Four weeks after the induction of diabetes, rats were exposed to cigarette smoke (200 μg L−1), 4 h daily, and 5 days per week for 4 weeks. Cigarette smoke did not affect the levels of plasma glucose, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol or non-esterified fatty acids in both control and diabetic rats under the experimental conditions. Cigarette smoke, however, significantly increased diabetes-induced glomerular hypertrophy and urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) excretion, suggesting exacerbation of diabetic kidney injury. Cigarette smoke promoted macrophage infiltration and fibrosis in the diabetic kidney. As expected, cigarette smoke increased oxidative stress in both control and diabetic rats. These data demonstrated that four weeks of exposure to cigarette smoke aggravated the progression of DKD in rats.

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.

scholarly journals The Protective Effect of Low-Dose Ethanol on Myocardial Fibrosis through Downregulating the JNK Signaling Pathway in Diabetic Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Ying Yu ◽  
Xian-Jie Jia ◽  
Wei-ping Zhang ◽  
Ting-ting Fang ◽  
Jie Hu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Myocardial Fibrosis ◽  
Low Dose ◽  
Volume Fraction ◽  
Diabetic Rats ◽  
Heart Weight ◽  
Hemodynamic Parameters ◽  
Sprague Dawley ◽  
Jnk Pathway ◽  
Ethanol Feeding

Objective. To investigate the effects of low dose ethanol feeding in diabetic rats and analyze its underlying mechanisms.Methods. Male Sprague-Dawley rats were divided into 4 groups: control (Con), diabetes at 4 weeks (DM4W), diabetes at 8 weeks (DM8W), and EtOH + DM8W. After 8 weeks, hemodynamic parameters were recorded and heart weight/body weight (H/B) and hydroxyproline (Hp) content in myocardium were measured. Morphology of collagen in myocardial tissue was observed with Masson’s trichrome staining method and collagen volume fraction (CVF) was analysed. The mRNA expression of ALDH2 was assessed with Real-Time PCR. The protein expressions of p-JNK and JNK were evaluated using western blot.Results. In contrast to Con group, there was no difference in hemodynamic parameters in DM4W group, but mean arterial pressure and heart rate were decreased in DM8W group, and the ratios of H/B, Hp, and CVF were markedly increased. ALDH2 mRNA expression was decreased, while the ratio of p-JNK/JNK were increased. Compared with DM8W group, the above indexes were improved in EtOH + DM8W group.Conclusion. With low dose ethanol intervention, enhanced ALDH2 expression can antagonize the happening of myocardial fibrosis in diabetic rats, which may be relevant with downregulating the JNK pathway.

Desired and side effects of the supplementation with l -glutamine and l -glutathione in enteric glia of diabetic rats

2016 ◽  
Vol 118 (6) ◽  
pp. 625-631 ◽  
Author(s):  
Cynthia Priscilla do Nascimento Bonato Panizzon ◽  
Jacqueline Nelisis Zanoni ◽  
Catchia Hermes-Uliana ◽  
Aline Rosa Trevizan ◽  
Camila Caviquioli Sehaber ◽  
...  
Keyword(s):  
Side Effects ◽  
Diabetic Rats ◽  
Enteric Glia

Electroacupuncture at Zusanli Rescues the Enteric Neuronal Loss in the Stomach of Diabetic Rats

2012 ◽  
Vol 18 (1) ◽  
pp. 5-14 ◽  
Author(s):  
Min Hu ◽  
Fan Du ◽  
Shi Liu
Keyword(s):  
High Frequency ◽  
Low Frequency ◽  
Neuronal Loss ◽  
Diabetic Rats ◽  
Enteric Neurons ◽  
Control Group ◽  
Sprague Dawley ◽  
Long Duration ◽  
Sprague Dawley Rats ◽  
Zusanli Acupoint

The purpose of this study was to investigate the effects of electroacupuncture at Zusanli acupoint on the enteric neuropathy in diabetic rats. Sprague–Dawley rats were divided into different groups depending on the total electroacupuncture span and frequency. The expression of nitric oxide synthase (nNOS), choline acetyltransferase (CHAT), protein gene product 9.5 (PGP9.5), and doublecortin was significantly decreased in the diabetic group compared with the control group. Long-term electroacupuncture at Zusanli with either high frequency or low frequency could increase the expression levels of nNOS, CHAT, PGP9.5, and doublecortin, and the increase was greater in the high-frequency group. But no obvious changes were seen in the short-term electroacupuncture groups. These results suggest that electroacupuncture at Zusanli can restore the deficiency of enteric neurons in diabetes partly but a comparative long duration of stimuli (6 weeks) is required. The increase of doublecortin may be involved in this positive process.

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