scholarly journals Treatment-Induced Neuropathy in Diabetes (TIND)—Developing a Disease Model in Type 1 Diabetic Rats

2021 ◽  
Vol 22 (4) ◽  
pp. 1571
Author(s):  
Petra Baum ◽  
Severin Koj ◽  
Nora Klöting ◽  
Matthias Blüher ◽  
Joseph Classen ◽  
...  
Keyword(s):  
Insulin Treatment ◽  
Diabetic Rats ◽  
Nerve Fibers ◽  
Rapid Decrease ◽  
High Dose ◽  
Abrupt Decrease ◽  
Initial Values ◽  
Intraepidermal Nerve Fiber Density ◽  
Acute Neuropathy ◽  
Conduction Velocities

Treatment-induced neuropathy in diabetes (TIND) is defined by the occurrence of an acute neuropathy within 8 weeks of an abrupt decrease in glycated hemoglobin-A1c (HbA1c). The underlying pathogenic mechanisms are still incompletely understood with only one mouse model being explored to date. The aim of this study was to further explore the hypothesis that an abrupt insulin-induced fall in HbA1c may be the prime causal factor of developing TIND. BB/OKL (bio breeding/OKL, Ottawa Karlsburg Leipzig) diabetic rats were randomized in three groups, receiving insulin treatment by implanted subcutaneous osmotic insulin pumps for 3 months, as follows: Group one received 2 units per day; group two 1 unit per day: and group three 1 unit per day in the first month, followed by 2 units per day in the last two months. We serially examined blood glucose and HbA1c levels, motor- and sensory/mixed afferent conduction velocities (mNCV and csNCV) and peripheral nerve morphology, including intraepidermal nerve fiber density and numbers of Iba-1 (ionized calcium binding adaptor molecule 1) positive macrophages in the sciatic nerve. Only in BB/OKL rats of group three, with a rapid decrease in HbA1c of more than 2%, did we find a significant decrease in mNCV in sciatic nerves (81% of initial values) after three months of treatment as compared to those group three rats with a less marked decrease in HbA1c <2% (mNCV 106% of initial values, p ≤ 0.01). A similar trend was observed for sensory/mixed afferent nerve conduction velocities: csNCV were reduced in BB/OKL rats with a rapid decrease in HbA1c >2% (csNCV 90% of initial values), compared to those rats with a mild decrease <2% (csNCV 112% of initial values, p ≤ 0.01). Moreover, BB/OKL rats of group three with a decrease in HbA1c >2% showed significantly greater infiltration of macrophages by about 50% (p ≤ 0.01) and a decreased amount of calcitonin gene related peptide (CGRP) positive nerve fibers as compared to the animals with a milder decrease in HbA1c. We conclude that a mild acute neuropathy with inflammatory components was induced in BB/OKL rats as a consequence of an abrupt decrease in HbA1c caused by high-dose insulin treatment. This experimentally induced neuropathy shares some features with TIND in humans and may be further explored in studies into the pathogenesis and treatment of TIND.

Short-term insulin treatment and aortic expressions of IGF-1 receptor and VEGF mRNA in diabetic rats

2002 ◽  
Vol 283 (5) ◽  
pp. H1761-H1768 ◽  
Author(s):  
Tsuneo Kobayashi ◽  
Katsuo Kamata
Keyword(s):  
Insulin Treatment ◽  
Diabetic Rats ◽  
High Dose ◽  
Short Term ◽  
Vegf Mrna ◽  
Significant Difference ◽  
Vascular Responsiveness ◽  
Enos Mrna ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

We investigated the relationship between the changes in vascular responsiveness and growth factor mRNA expressions induced by 1-wk treatment with high-dose insulin in control and established streptozotocin (STZ)-induced diabetes. Aortas from diabetic rats, but not those from insulin-treated diabetic rats, showed impaired endothelium-dependent relaxation in response to ACh (vs. untreated controls). The ACh-induced nitrite plus nitrate (NOx) level showed no significant difference between controls and diabetics. Insulin treatment increased NOx only in diabetics. In diabetics, insulin treatment significantly increased the aortic expressions of endothelial nitric oxide synthase (eNOS) mRNA and VEGF mRNA. The expression of IGF-1 mRNA was unaffected by diabetes or by insulin treatment. In contrast, the mRNA for the aortic IGF-1 receptor was increased in diabetics and further increased in insulin-treated diabetics. In aortic strips from age-matched control rats, IGF-1 caused a concentration-dependent relaxation. This relaxation was significantly stronger in strips from STZ-induced diabetic rats. These results suggest that in STZ-diabetic rats, short-term insulin treatment can ameliorate endothelial dysfunction by inducing overexpression of eNOS and/or VEGF mRNAs possibly via IGF-1 receptors. These receptors were increased in diabetes, perhaps as result of insulin deficiency.

Effects of interrupted insulin treatment on fetal outcome of pregnant diabetic rats

Diabetes ◽  
1989 ◽  
Vol 38 (6) ◽  
pp. 764-772 ◽  
Author(s):  
R. S. Eriksson ◽  
L. Thunberg ◽  
U. J. Eriksson
Keyword(s):  
Insulin Treatment ◽  
Fetal Outcome ◽  
Diabetic Rats ◽  
Pregnant Diabetic

Effect of atorvastatin on the angiogenic responsiveness of coronary endothelial cells in normal and streptozotocin (STZ) induced diabetic rats

2014 ◽  
Vol 92 (4) ◽  
pp. 338-349 ◽  
Author(s):  
Kiranj K. Chaudagar ◽  
Anita A. Mehta
Keyword(s):  
Endothelial Cells ◽  
Low Dose ◽  
Ischemia Reperfusion ◽  
Late Phase ◽  
Diabetic Rats ◽  
Lipid Lowering ◽  
Diabetic Rat ◽  
High Dose ◽  
Atorvastatin Treatment ◽  
Coronary Endothelial Cells

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.

scholarly journals NEUROPROTECTION OF ABELMOSCHUS ESCULENTUS L. AGAINST DIABETIC NEUROPATHY

2018 ◽  
Vol 11 (15) ◽  
pp. 28
Author(s):  
Lee Wei Yang ◽  
Santosh Fattepur ◽  
Kiran Chanabasappa Nilugal ◽  
Fadli Asmani ◽  
Eddy Yusuf ◽  
...  
Keyword(s):  
Body Weight ◽  
Sciatic Nerve ◽  
Diabetic Neuropathy ◽  
Performance Test ◽  
Neuroprotective Effect ◽  
Thermal Hyperalgesia ◽  
Diabetic Rats ◽  
Nerve Fibers ◽  
Abelmoschus Esculentus ◽  
Rotarod Performance

Objective: The present study was designed to determine the neuroprotective effect of Abelmoschus esculentus L. on alloxan-induced diabetic neuropathy in rats.Methods: Diabetes was induced in rats with a single intraperitoneal injection of alloxan monohydrate (130 mg/kg b.w). The ethanol extract of A. esculentus L. at a dose of 100 and 200 mg/kg of body weight was administered at single dose per day to alloxan-induced diabetic rats for 21 days. The fasting blood glucose was screened in the intermittent on day 0, day 14, and day 21. Behavioral tests such as thermal hyperalgesia test and rotarod performance test were performed to assess the thermal sensitivity and muscle grip strength. At the end of the study period, experimental animals were sacrificed and sciatic nerve tissues were obtained for histopathological investigation.Results: Animals treated with A. esculentus L. extarct at a dose of 200 mg/kg of body weight significantly reduced (p<0.05) in hyperglycemia and thermal hyperalgesia and significantly increased (p<0.05) in rotarod performance. The sciatic nerve fiber of diabetic rats receiving 200 mg/kg of body weight of A. esculentus L. extract also shows no swelling of nerve fibers, and lesser demyelination was observed.Conclusion: These findings demonstrate that A. esculentus L. exhibits significant antidiabetic and neuroprotective effect against alloxan-induced diabetic neuropathy in rats.

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 Insulin treatment reverses the increase in atrogin-1 expression in atrophied skeletal muscles of diabetic rats with acute joint inflammation

2018 ◽  
Vol Volume 14 ◽  
pp. 275-286 ◽  
Author(s):  
Clara Maria Pinheiro-Dardis ◽  
Vânia Ortega Gutierres ◽  
Renata Pires Assis ◽  
Sabrina Messa Peviani ◽  
Gabriel Borges Delfino ◽  
...  
Keyword(s):  
Skeletal Muscles ◽  
Insulin Treatment ◽  
Joint Inflammation ◽  
Diabetic Rats

Effects of refeeding of undernourished and insulin treatment of diabetic neonatal rats on IGF and IGFBP

1996 ◽  
Vol 271 (2) ◽  
pp. E223-E231 ◽  
Author(s):  
L. Goya ◽  
F. Rivero ◽  
M. A. Martin ◽  
R. Arahuetes ◽  
E. R. Hernandez ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Growth Factor ◽  
Mrna Expression ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
Insulin Like Growth Factor ◽  
Neonatal Rats ◽  
Igf I ◽  
Serum Gh

The effect of refeeding and insulin treatment of undernourished and diabetic neonatal rats, respectively, on the regulation of insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) was investigated. The changes in body weight, insulinemia, glycemia, serum IGF-I, and growth hormone (GH) as well as the increase of the 30-kDa IGFBP in undernourished and diabetic neonatal rats previously shown elsewhere were reversed by refeeding and insulin treatment, respectively. Also, changes in liver mRNA expression of IGF-I and-II and IGFBP-1 and -2 were restored in refed undernourished and IGF-I and IGFBP-1 levels recovered in insulin-treated diabetic rats. However, serum GH was still below normal after rehabilitation in both situations. Thus the present results support the idea of a GH-independent IGF/ IGFBP regulation mediated by a balance of insulin and nutrients as has already been suggested in previous neonatal studies.

Insulin treatment fails to abolish the teratogenic potential of serum from diabetic rats

1996 ◽  
Vol 134 (4) ◽  
pp. 459-466 ◽  
Author(s):  
Parri Wentzel ◽  
Ulf J Eriksson
Keyword(s):  
Glucose Concentration ◽  
Insulin Treatment ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Normal Serum ◽  
Serum Factors ◽  
Crown Rump Length ◽  
Increased Risk ◽  
Control Serum ◽  
Teratogenic Potential

Wentzel P, Eriksson UJ. Insulin treatment fails to abolish the teratogenic potential of serum from diabetic rats. Eur J Endocrinol 1996;134:459–66. ISSN 0804–4643 Maternal diabetes during pregnancy constitutes an increased risk for congenital malformations in the offspring. Previous studies have identified several serum components with teratogenic activity, e.g. glucose and β-hydroxybutyrate, but have also suggested that the teratogenic influence of the diabetic environment on the developing embryo is multifactorial and may depend upon changed concentrations of several maternal metabolites. In the present investigation we aimed to assess the teratological impact of small, concomitant alterations in a series of metabolites, particularly those not previously identified as teratogens. We thus investigated the influence of a mild diabetic environment by culturing gestational day-9 rat embryos in serum from insulin-treated diabetic rats for 48 h in vitro, and compared the embryonic outcome with that obtained after culture in normal serum and in serum from manifestly diabetic rats without insulin treatment. The glucose concentration was adjusted to 10 or 30 mmol/l in the cultures, and the embryos were evaluated with respect to crown–rump length, protein and DNA content, number of somites and malformation score (comparing major, minor or no malformations). We found that increased glucose levels caused embryonic maldevelopment in both normal and diabetic serum, and that despite normalization of the diabetic state, the serum from the insulin-treated diabetic rats caused more growth retardation than the nondiabetic control serum. The normalized diabetic serum was also more teratogenic than the normal serum at the low glucose concentration, whereas the serum from the manifestly diabetic rats tended to cause more dysmorphogenesis at 30 mmol/l glucose than both the normal and normalized diabetic serum. The results suggest that the teratogenicity of maternal serum in diabetic pregnancy is not mediated exclusively by increased concentrations of glucose and ketone bodies. The efforts to diminish the teratogenic effects of a diabetic environment should therefore include normalization of a multitude of serum factors, including glucose and ketone bodies. Parri Wentzel, Department of Medical Cell Biology, University of Uppsala, Biomedicum, PO Box 571, S-751 23 Uppsala, Sweden

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