scholarly journals Perturbation of the mucosa-associated anaerobic gut microbiota in streptozotocin-induced diabetic rats

2021 ◽  
Vol 65 (1) ◽  
pp. 75-84
Author(s):  
Roland Wirth ◽  
Nikolett Bódi ◽  
Zita Szalai ◽  
Lalitha Chandrakumar ◽  
Gergely Maróti ◽  
...  
Keyword(s):  
Insulin Treatment ◽  
Relative Number ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Tissue Samples ◽  
Next Generation Dna Sequencing ◽  
Chronic Hyperglycaemia ◽  
And Control ◽  
Diabetic Rat Model ◽  
Anaerobic Environment

Our aim was to map the gut region-specific differences of the mucosa-associated microbiome distribution in a streptozotocin-induced diabetic rat model. Tissue samples from the duodenum, ileum and colon were collected 10 weeks after the onset of hyperglycaemia to analyse the mucosa-associated microbiota using next-generation DNA sequencing. Striking differences were observed in the mucosa-associated microbiota of the duodenum between diabetic and control rats. A significant invasion of the aerobic genus Mycoplasma was apparent in diabetes, and the abundance of the anaerobic phylum Firmicutes decreased massively. It is noteworthy that insulin treatment eliminated the Mycoplasma invasion in the duodenum and apparently restored the anaerobic environment in the mucosa. In the ileum the abundance of the phylum Firmicutes increased in the diabetic samples. Although the proportion of the phylum Proteobacteria decreased moderately, its composition changed significantly, and insulin treatment induced only minor alterations. In the diabetic samples of colon, the abundance of the phylum Firmicutes decreased slightly, the relative number of the bacteria in the phylum Bacteroidetes increased strongly as compared to the control values, and after insulin treatment this increase was more significant. Chronic hyperglycaemia has the most prominent effect on the mucosa-associated microbiota in the duodenum.

Aspartame Administration and Insulin Treatment Altered Brain Levels of CYP2E1 and CYP3A2 in Streptozotocin-Induced Diabetic Rats

2014 ◽  
Vol 33 (4) ◽  
pp. 325-331 ◽  
Author(s):  
Rosario Nosti-Palacios ◽  
Josefina Gómez-Garduño ◽  
Dora Molina-Ortiz ◽  
Raúl Calzada-León ◽  
Víctor Manuel Dorado-González ◽  
...  
Keyword(s):  
Insulin Treatment ◽  
Combined Treatment ◽  
Diabetic Rats ◽  
Male Rat ◽  
Diabetic Rat ◽  
Toxic Substances ◽  
Protein Activity ◽  
Tissue Samples ◽  
Juvenile Diabetic ◽  
The Brain

This study demonstrates that aspartame consumption and insulin treatment in a juvenile diabetic rat model leads to increase in cytochrome P450 (CYP) 2E1 and CYP3A2 isozymes in brain. Diabetes mellitus was induced in postweaned 21-day-old Wistar male rat by streptozotocin. Animals were randomly assigned to one of the following groups: untreated control, diabetic (D), D-insulin, D-aspartame, or the D-insulin + aspartame-treated group. Brain and liver tissue samples were used to analyze the activity of CYP2E1 and CYP3A2 and protein levels. Our results indicate that combined treatment with insulin and aspartame in juvenile diabetic rats significantly induced CYP2E1 in the cerebrum and cerebellum without modifying it in the liver, while CYP3A2 protein activity increased both in the brain and in the liver. The induction of CYP2E1 in the brain could have important in situ toxicological effects, given that this CYP isoform is capable of bioactivating various toxic substances. Additionally, CYP3A2 induction in the liver and brain could be considered a decisive factor in the variation of drug response and toxicity.

scholarly journals Oxidative Stress in Rats After 60 Days of Hypergalactosemia or Hyperglycemia

2003 ◽  
Vol 22 (6) ◽  
pp. 423-427 ◽  
Author(s):  
Mary Otsyula ◽  
Matthew S. King ◽  
Tonya G. Ketcham ◽  
Ruth A. Sanders ◽  
John B. Watkins
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Glutathione Peroxidase ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Glutathione Disulfide ◽  
Hepatic Lipid Peroxidation ◽  
Streptozotocin Diabetic Rats

Two of the models used in current diabetes research include the hypergalactosemic rat and the hyperglucosemic, streptozotocin-induced diabetic rat. Few studies, however, have examined the concurrence of these two models regarding the effects of elevated hexoses on biomarkers of oxidative stress. This study compared the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase and the concentrations of glutathione, glutathione disulfide, and thiobarbituric acid reactants (as a measure of lipid peroxidation) in liver, kidney, and heart of Sprague-Dawley rats after 60 days of either a 50% galactose diet or insulin deficiency caused by streptozotocin injection. Most rats from both models developed bilateral cataracts. Blood glucose and glycosy-lated hemoglobin A1c concentrations were elevated in streptozotocin diabetic rats. Streptozotocin diabetic rats exhibited elevated activities of renal superoxide dismutase, cardiac catalase, and renal and cardiac glutathione peroxidase, as well as elevated hepatic lipid peroxidation. Insulin treatment of streptozotocin-induced diabetic rats normalized altered markers. In galactosemic rats, hepatic lipid peroxidation was increased whereas glutathione reductase activity was diminished. Glutathione levels in liver were decreased in diabetic rats but elevated in the galactosemic rats, whereas hepatic glutathione disulfide concentrations were decreased much more in diabetes than in galactosemia. Insulin treatment reversed/prevented all changes caused by streptozotocin-induced diabetes. Lack of concomitance in these data indicate that the 60-day galactose-fed rat is not experiencing the same oxidative stress as the streptozotocin diabetic rat, and that investigators must be cautious drawing conclusions regarding the concurrence of the effects of the two animal models on oxidative stress biomarkers.

scholarly journals Nicotine Exposure Exacerbates Development of Cataracts in a Type 1 Diabetic Rat Model

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Nima Tirgan ◽  
Gabriela A. Kulp ◽  
Praveena Gupta ◽  
Adam Boretsky ◽  
Tomasz A. Wiraszka ◽  
...  
Keyword(s):  
Rat Model ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Positive Trend ◽  
Sprague Dawley ◽  
Nicotine Treatment ◽  
Sprague Dawley Rats ◽  
Diabetic Rat Model

Diabetes and smoking are known risk factors for cataract development. In this study, we evaluated the effect of nicotine on the progression of cataracts in a type 1 diabetic rat model. Diabetes was induced in Sprague-Dawley rats by a single injection of 65 mg/kg streptozotocin. Daily nicotine injections were administered subcutaneously. Forty-five rats were divided into groups of diabetics with and without nicotine treatment and controls with and without nicotine treatment. Progression of lens opacity was monitored using a slit lamp biomicroscope and scores were assigned. To assess whether systemic inflammation played a role in mediating cataractogenesis, we studied serum levels of eotaxin, IL-6, and IL-4. The levels of the measured cytokines increased significantly in nicotine-treated and untreated diabetic animals versus controls and demonstrated a positive trend in the nicotine-treated diabetic rats. Our data suggest the presence of a synergistic relationship between nicotine and diabetes that accelerated cataract formation via inflammatory mediators.

Acute insulin withdrawal contributes to ischemic heart failure in spontaneously diabetic BB Wistar rats

1990 ◽  
Vol 68 (3) ◽  
pp. 462-466 ◽  
Author(s):  
Gary D. Lopaschuk ◽  
Marguerite A. Spafford
Keyword(s):  
Fatty Acids ◽  
Metabolic Control ◽  
Wistar Rats ◽  
Insulin Treatment ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Metabolic Demand ◽  
Significant Deterioration ◽  
Direct Demonstration

The contribution of poor metabolic control to myocardial ischemic failure was determined in isolated working hearts from insulin-dependent BB Wistar rats. Removal of insulin treatment 24 h prior to study (uncontrolled diabetic rats) resulted in significant increases in serum glucose, serum fatty acids, and myocardial triglyceride, compared with animals in which insulin treatment was not withheld (insulin-treated diabetic rats). Isolated working hearts obtained from these two groups were subjected to a 40% reduction in coronary flow in the presence of a maintained metabolic demand (hearts were paced at 200 beats/min and perfused at an 80 mmHg (1 mmHg = 133.3 Pa) left aortic afterload, 11.5 mmHg left atrial preload). Within 15 min of ischemia, a significant deterioration of mechanical function occurred in the uncontrolled diabetic rats, whereas function was maintained in the insulin-treated diabetic rats. Oxygen consumption by the two groups of hearts was similar prior to the onset of ischemia and decreased during ischemia in parallel with the work performed by the hearts. This suggests that the accelerated failure rate in uncontrolled diabetic rat hearts is unlikely a result of an increased oxygen requirement. These data are a direct demonstration that acute changes in metabolic control of the diabetic can contribute to the severity of myocardial ischemic injury.Key words: diabetes, heart, ischemia, fatty acids.

Insulin reversal of biochemical changes in hearts from diabetic rats

1986 ◽  
Vol 251 (3) ◽  
pp. H670-H675
Author(s):  
S. Bhimji ◽  
D. V. Godin ◽  
J. H. McNeill
Keyword(s):  
Insulin Treatment ◽  
Serum Insulin ◽  
Complete Recovery ◽  
Magnesium Content ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Biochemical Changes ◽  
Diabetic Rat ◽  
Lysosomal Hydrolase ◽  
Rat Hearts

Reversal of myocardial biochemical changes with insulin treatment (4 and 8 wk) was studied in 8 and 12 wk streptozotocin (STZ)-diabetic rats. STZ-induced diabetes was characterized by elevations in blood glucose, serum cholesterol, and triglycerides and depressed serum insulin levels. Insulin treatment for 4 and 8 wk completely restored the serum alterations to control values. The polyuria, polydipsia, and polyphagia were also markedly diminished by the insulin treatment. Diabetic rats had pronounced decreases in body, heart, and left ventricular weights, all of which were completely reversed by the insulin treatment. Hydroxyproline accumulation in diabetic rat hearts was only reversed by the 8-wk and not by the 4-wk insulin treatment. STZ produced a significant depletion of left ventricular magnesium content as well as depression of K+-stimulated sarcoplasmic reticulum and myofibrillar ATPase activities. Both the 4- and 8-wk insulin treatment produced a complete recovery of the myocardial magnesium content. No significant changes in sarcolemmal Na+-K+-ATPase and K+-stimulated p-nitrophenyl phosphatase activities were observed in diabetic animals compared with control. The decreased latency of the lysosomal hydrolase, N-acetyl-beta-glucosaminidase, and the increased collagen deposition observed in the diabetic hearts were only partially reversed by the 4-wk insulin treatment, but completely reversed by the 8-wk treatment period.

Reduced activity of mtTFA decreases the transcription in mitochondria isolated from diabetic rat heart

2002 ◽  
Vol 282 (4) ◽  
pp. E778-E785 ◽  
Author(s):  
Akio Kanazawa ◽  
Yoshihiko Nishio ◽  
Atsunori Kashiwagi ◽  
Hidetoshi Inagaki ◽  
Ryuichi Kikkawa ◽  
...  
Keyword(s):  
Insulin Treatment ◽  
Mitochondrial Protein ◽  
Mitochondrial Respiratory Chain ◽  
Binding Activity ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Mitochondrial Transcription Factor ◽  
Loop Region ◽  
Rat Hearts ◽  
D Loop

To evaluate abnormalities in the mitochondrial transcription factor A (mtTFA) function as a cause of mitochondrial dysfunction in diabetes, we measured the mRNA contents of the proteins consisting of the mitochondrial respiratory chain as well as transcriptional and translational activities in the mitochondria isolated from controls and streptozotocin-induced diabetic rat hearts. Using Northern blot analysis, we found 40% reduced mRNA contents of mitochondrial-encoded cytochrome b and ATP synthase subunit 6 in diabetic rat hearts compared with control rats ( P< 0.05). These abnormalities were completely recovered by insulin treatment. Furthermore, the mitochondrial activities of transcription and translation were decreased significantly in mitochondria isolated from diabetic rats by 60% ( P < 0.01) and 71% ( P < 0.01), respectively, compared with control rats. The insulin treatment also completely normalized these abnormalities in diabetic rats. Consistently, gel retardation assay showed a reduced binding of mtTFA to the D-loop of mitochondrial DNA in diabetic rats, although there was no difference in the mtTFA mRNA and protein content between the two groups. On the basis of these findings, a reduced binding activity of mtTFA to the D-loop region in the hearts of diabetic rats may contribute to the decreased mitochondrial protein synthesis.

scholarly journals Effects of Type II diabetes on exercising skeletal muscle blood flow in the rat

2010 ◽  
Vol 109 (5) ◽  
pp. 1347-1353 ◽  
Author(s):  
Steven W. Copp ◽  
K. Sue Hageman ◽  
Brad J. Behnke ◽  
David C. Poole ◽  
Timothy I. Musch
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Type Ii Diabetes ◽  
Blood Glucose Concentration ◽  
Muscle Blood Flow ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Type Ii ◽  
The Individual ◽  
And Control

The purpose of the present investigation was to examine the muscle hyperemic response to steady-state submaximal running exercise in the Goto-Kakizaki (GK) Type II diabetic rat. Specifically, the hypothesis was tested that Type II diabetes would redistribute exercising blood flow toward less oxidative muscles and muscle portions of the hindlimb. GK diabetic ( n = 10) and Wistar control ( n = 8, blood glucose concentration, 13.7 ± 1.6 and 5.7 ± 0.2 mM, respectively, P < 0.05) rats were run at 20 m/min on a 10% grade. Blood flows to 28 hindlimb muscles and muscle portions as well as the abdominal organs and kidneys were measured in the steady state of exercise using radiolabeled 15-μm microspheres. Blood flow to the total hindlimb musculature did not differ between GK diabetic and control rats (161 ± 16 and 129 ± 15 ml·min−1·100g−1, respectively, P = 0.18). Moreover, there was no difference in blood flow between GK diabetic and control rats in 20 of the individual muscles or muscle parts examined. However, in the other eight muscles examined that typically are comprised of a majority of fast-twitch glycolytic (IIb/IIdx) fibers, blood flow was significantly greater (i.e., ↑31–119%, P < 0.05) in the GK diabetic rats. Despite previously documented impairments of several vasodilatory pathways in Type II diabetes these data provide the first demonstration that a reduction of exercising muscle blood flow during submaximal exercise is not an obligatory consequence of this condition in the GK diabetic rat.

scholarly journals Fushiming Capsule Attenuates Diabetic Rat Retina Damage via Antioxidation and Anti-Inflammation

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Mengshan He ◽  
Pan Long ◽  
Lunfeng Guo ◽  
Mingke Zhang ◽  
Siwang Wang ◽  
...  
Keyword(s):  
Rat Model ◽  
Day Treatment ◽  
Outer Nuclear Layer ◽  
Diabetic Rats ◽  
Retinal Function ◽  
Diabetic Rat ◽  
Full Field ◽  
Rat Retina ◽  
Protein Levels ◽  
Diabetic Rat Model

Aims. Diabetic retinopathy (DR) remains one of the leading causes of acquired blindness. Fushiming capsule (FSM), a compound traditional Chinese medicine, is clinically used for DR treatment in China. The present study was to investigate the effect of FSM on retinal alterations, inflammatory response, and oxidative stress triggered by diabetes. Main Methods. Diabetic rat model was induced by 6-week high-fat and high-sugar diet combined with 35 mg/kg streptozotocin (STZ). 30 days after successful establishment of diabetic rat model, full field electroretinography (ffERG) and optical coherence tomography (OCT) were performed to detect retinal pathological alterations. Then, FSM was administered to diabetic rats at different dosages for 42-day treatment and diabetic rats treated with Calcium dobesilate (CaD) capsule served as the positive group. Retinal function and structure were observed, and retinal vascular endothelial growth factor-α (VEGF-α), glial fibrillary acidic (GFAP), and vascular cell adhesion protein-1 (VCAM-1) expressions were measured both on mRNA and protein levels, and a series of blood metabolic indicators were also assessed. Key Findings. In DR rats, FSM (1.0 g/kg and 0.5 g/kg) treatment significantly restored retinal function (a higher amplitude of b-wave in dark-adaptation 3.0 and OPs2 wave) and prevented the decrease of retinal thickness including inner nuclear layer (INL), outer nuclear layer (ONL), and entire retina. Additionally, FSM dramatically decreased VEGF-α, GFAP, and VCAM-1 expressions in retinal tissues. Moreover, FSM notably improved serum antioxidative enzymes glutathione peroxidase, superoxide dismutase, and catalase activities, whereas it reduced serum advanced glycation end products, methane dicarboxylic aldehyde, nitric oxide, and total cholesterol and triglycerides levels. Significance. FSM could ameliorate diabetic rat retina damage possibly via inhibiting inflammation and improving antioxidation.

Intracellular protons inhibit transient outward K+ current in ventricular myocytes from diabetic rats

1996 ◽  
Vol 271 (5) ◽  
pp. H2154-H2161 ◽  
Author(s):  
Z. Xu ◽  
K. P. Patel ◽  
G. J. Rozanski
Keyword(s):  
Ventricular Myocytes ◽  
External Solution ◽  
Cell Voltage ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Intracellular Acidosis ◽  
K Current ◽  
Acid Load ◽  
Dimethyl Amiloride ◽  
And Control

This study examined the effects of protons on cardiac ion channel function in early stages of diabetes mellitus. Transient outward (I(to)) and inward rectifier K+ (IK1) currents were recorded by the whole cell, voltage-clamp technique in ventricular myocytes isolated from hearts of streptozotocin-induced diabetic and control rats. Proton concentration was controlled by independently varying the pH of buffered external or pipette (pHp) solutions. External acidification did not alter I(to) in diabetic rat myocytes when initiated after intracellular dialysis with standard pHp 7.2, but when these cells were dialyzed with acidic pHp (6.6 or 6.0), I(to) density was significantly reduced. Low pHp also reduced I(to) density more in cells from diabetic rats than in controls, whereas alkaline pHp had no effect on either group of cells compared with standard pHp 7.2. In control myocytes dialyzed with pHp 6.0, block of Na+/H+ exchange with 5-(N,N-dimethyl)-amiloride (DMA) or Na(+)-free external solution further reduced I(to) density compared with pHp 6.0 alone, whereas these treatments had less effect on acid-dialyzed cells from diabetic rats. Dialysis with pHp to 6.0 did not alter IK1 in either group of cells compared with standard pHp 7.2, but when done in the presence of DMA or Na(+)-free conditions, IK1 density in both groups was significantly reduced by nearly the same amount. We conclude that intracellular protons inhibit I(to) channels in ventricular myocytes from diabetic and control rats, but that for a given acid load, inhibition is markedly greater in diabetics. This difference may be explained by a diabetes-induced decrease in Na+/H+ exchange that limits proton extrusion during intracellular acidosis. Moreover, acidosis may differentially suppress I(to) and IK1, suggesting that these K+ channels exhibit dissimilar sensitivities to intracellular protons.

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