For the most part these have followed the first demonstration of a conduction deficit in diabetic rats,90 by concentrating on MNCV. Third, rats in which transplants of pancreatic islet cells do not succeed in correcting glucose levels also show improvement in renal results.12 As with retinopathy, studies of nephropathy in animal models can lend support to, but cannot prove, the glucose hypothesis. Copyright © 2021 Elsevier B.V. or its licensors or contributors. The deficit is preventable in the short term (generally about 1 month) by maintenance of tight glycemic control with insulin.124,200 A similar deficit in MNCV is present in the BB rat when control of glycemia is allowed to lapse to a minimal life-preserving level.125,203 Improvement of the quality of glycemic control attenuates the MNCV deficit.126 More detailed examination of nerve conduction in different nerve trunks of STZ-diabetic rats revealed velocity deficits in all branches of the innervation of the lower limb, including some that carry predominantly sensory fibers.52. Administration of alloxan (150 mg/kg body weight, i.p.) ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. Alloxan-induced diabetes, a common model for evaluating the glycemic-control potential of therapeutic compounds and plants extracts in experimental studies. The antidiabetic effect of the complex was significantly more pronounced as compared to the similar effect of both the monopreparations, HPβCD and SER. Department of Pharmacognosy, Institute of Pharmacy, Bundelkhand University, Jhansi, (U.P. In vitrostudies proved that alloxan mediate cytotoxic action by production of ROS that cause destruction of β- cells.24,25 Individuals with a common missense variant (rs13266634; R325W) in SLC30A8, a gene encoding a ZnT8 in the β cell, demonstrate a lower early insulin response to glucose and an increased risk of T2D. However in diabetes research, among the diverse models, chemically-induced are highly preferable by investigators covering alloxan- and streptozotocin-induced rodent models. To test this hypothesis, a prospective double-blind, randomized, placebo-controlled clinical trial, included 56 normal glucose-tolerant obese women who were treated with 30 mg Zn daily for 4 weeks. Streptozotocin and alloxan cause similar changes, and additionally the spontaneously diabetic BB Wistar rat shows virtually identical patterns of tissue antioxidant enzyme changes.50 Furthermore, these alterations are preventable by insulin treatment.10,50,188,189 The common mechanism of increased oxidative stress is, therefore, diabetes (hyperglycemia) and not its mode of induction. Cu(II)-dependent DNA damage increased with the concentration of alloxan and NADH. ABSTRACT. The assertion that pathogenetic factors other than polyol pathway flux and metabolites contribute to the development of a shortfall in MNCV in chronic diabetes receives support from work with gangliosides. Insulin did not change in the placebo group but was significantly decreased in the Zn-supplemented group. 108 African Journal of Reproductive Health African Journal of Reproductive Health Vol. Alloxan is a pyrimidine derivative, which became of interest in diabetes research when it was reported to be diabetogenic. Their contribution may be prevented by ganglioside treatment. © 2018 The Lithuanian University of Health Sciences. The duration of the cherries treatment was 30 days in which single dose of extracts (200mg/kg) were oral administered to diabetic rats. Alloxan-induced and Insulin-resistant Diabetes Mellitus affect Semen Parameters and Impair Spermatogenesis in Male Rats. 10 No.3 December 2006 using the new improved Neubauer counting chamber for determination of the concentration of spermatozoa, sperm motility and sperm density. Groups included (I) non-diabetic control, (II) thiamine (30 mg/l, IP), (III) alloxan-induced diabetic mice, (IV) diabetes + ZnO NPs (0.1 mg/kg IP), (V) diabetes + ZnO NPs (0.5 mg/kg IP), (VI) diabetes + ZnO NPs (0.1 mg/kg IP) + thiamine (30 mg/l, IP), and (VII) diabetes + ZnO NPs (0.5 mg/kg IP) + thiamine (30 mg/l, … The most convincing animal studies were done by Engerman and colleagues with alloxan-induced diabetes in dogs.10,11 The diabetic dogs developed retinopathy with microaneurysms and pericyte loss similar to those seen in diabetic humans. The effect of Zn supplementation on insulin resistance and components of metabolic syndrome in prepubertal obese children has been investigated using a triple-masked, randomized, placebo-controlled cross-over trial among 60 obese Iranian children. ), India. With STZ-induced diabetes of longer duration, the beneficial effects of ARIs against MNCV deficits are less marked. Zn supplementation increased serum Zn by 15% and urinary Zn by 56%. Glucose-lowering effects of M. oleifera extracts have been reported. Glycogen synthase activities and glycogen contents were higher in extract-treated rats compared with rats receiving metformin or saline and the extract improved glucose uptake. After 12 h, a 10% glucose solution was offered to the animals to prevent hypoglycemia (27,28). In addition, high-sensitivity C-reactive protein (hs-CRP) and markers of insulin resistance were decreased significantly in the Zn group but increased in the placebo group. Intraperitoneal glucose tolerance was assessed and serum glucose, insulin, and lipids were measured at the end of the experiment. By continuing you agree to the use of cookies. It also normalized the reduced mRNA expression of fatty acid synthase in the liver of diabetic rats. The only cogent neurophysiologic argument to explain the deficit has come from the suggestion of increased refractoriness of nodes of Ranvier in diabetes leading to deferred activation and propagation.37,38,155 This change may derive from impairment of voltage-gated Na+ channels, but it has also been attributed to reduced driving gradient for Na+, and this has been attributed in turn to impaired activation of Na+, K+-ATPase.126 The hypothesis then suggests that the depletion of myo-inositol, derived from exaggerated polyol pathway flux, limits the synthesis of inositol-containing phospholipids and that DAG, which is derived from these lipids, regulates activation of subunits of the membrane Na+, K+-ATPase.125 This hypothesis still lacks substantive proof, and the role of impaired Na+, K+-ATPase activity in the development of conduction deficits remains contentious. Philip J. Randle, in Comprehensive Biochemistry, 2003. Diabetes mellitus is the most common endocrine disorder that impairs glucose … It is normally and largely compromised in diabetes. They found that leaf extract counteracted the alloxan-induced diabetic effects in rats as it normalized the elevated serum levels of glucose, triglycerides, cholesterol, and MDA, and normalized mRNA expression of the gluconeogenic enzyme pyruvate carboxylase in hepatic tissues. We enhanced water-solubility of sertraline by complexation with 2-hydroxypropyl-β-cyclodextrin (HPβCD) and evaluated the pharmacological properties of the HPβCD:sertraline complex in rats with alloxan-induced diabetes. Notes: (MT) ND, no detection of pancreatic MT content; 1 (12) w, 1 week prior to STZ and continued 12 weeks after STZ; inhibiting nuclear factor-κB and/or AP1, through inhibition of pancreatic nuclear factor-κB and/or AP1 activation; ALX, alloxan; NOD, nonobese diabetes. It is possible to distill this work into a few salient, unequivocal findings. The responses are accompanied by corresponding inverse changes in plasma insulin and sequential ultrastructural changes resulting in necrotic beta cell death. This has been demonstrated for ICI 105552,329 sorbinil,376 zenarestat,169 tolrestat,224 ponalrestat,294 and fidarestat.161 Furthermore, a group of rats left untreated over the first 3 weeks of their STZ-induced diabetes, and displaying a significant MNCV deficit at that time, showed a return of MNCV to normal levels over 3 weeks of treatment with sorbinil.331 Thus in the short term the deficit is reversible. LLEWELYN, ... P.K. There were eight studies comparing the effects of Zn supplementation on lipid parameters in patients with T2D. As the paramutational process continues, the regulator genes involved in carbohydrate metabolism become altered in some individuals, permitting expression of diabetes in these people, despite normal parents or even a monozygotic twin. Second, other factors contribute to reduced MNCV with longer durations of diabetes. In diabetic rats, alloxan diabetes was induced by intraperitoneally injecting 1 ml of 5% alloxan at the beginning of the study Group Glycaemic Treatment status A Nondiabetic 1 ml distilled water (intraperitoneally) per day for 10 days B Diabetic 1 ml of a 5% solution of alloxan monohydrate at a dose of 125 mg/kg C Diabetic Alloxan monohydrate+glibenclamide (10 mg/kg). Oxidative stress occurs in experimental diabetes induced by streptozotocin and alloxan, and in the diabetic BB Wistar rat. Administration of either (-)epicatechin or (+)catechin (250 mg/kg, i.p. Thus, although the proposal of Sima and co-workers293 that axoglial dysjunction occurs in diabetic nerve is based on chance observations of electron micrographs, it could be verified by molecular biology and represents a cogent explanation for the development of a conduction deficit based on phenotype breakdown in either Schwann cell or neuron. Studies of glycemic control and neuropathy have also supported the glucose hypothesis.24, Vyacheslav Buko, ... Ilya Zavodnik, in Nano- and Microscale Drug Delivery Systems, 2017. Yassa and Tohamy also demonstrated that leaf extract ameliorates streptozotocin-induced diabetes mellitus in adult rats (Gupta et al., 2012; Yassa and Tohamy, 2014). Even though glucokinase activity normally is developing rapidly in the rat liver during the third week of life, its induction may be inhibited by starvation between the twenty- first and twenty-fourth day of life (Walker and Holland, 1965). intraperitoneally to induce diabetes in 8 h fasted [ 19 ] male Sprague Dawley rats weighing 180–200 g. After one hour of alloxan administration, the animals were given feed ad libitum. There was a 56% reduction in brain lactate concentration, but pyruvate levels were unchanged. Production and hosting by Elsevier Sp. I was able to show in perfused rat heart that inhibition of fatty acid oxidation with 2-bromostearate reversed the insulin resistance in cardiac muscle in alloxan diabetes [24]. The hemimandibles were removed and submitted to radiographical and histopathological procedures. Complex patterns of changes in antioxidant enzymes have been described in different tissues in streptozocin diabetes.188,189 Liver and kidney have reduced catalase and SOD. Abd El Latif et al. These results suggest that besides lifestyle modification, Zn supplementation may be considered as a useful and safe additional intervention treatment for improvement of cardiometabolic risk factors related to childhood obesity. L'alloxane exerçant une toxicité sélective sur les cellules pancréatiques productrices d'insuline, il est utilisé en laboratoire pour induire un diabète insulinoprive sur des modèles animaux. In rats with STZ-induced diabetes of 6 months' duration, daily administration of the ARI ponalrestat had little effect on the conduction deficit.358 However, this study also revealed that administration of background insulin (twice-weekly doses of the long-acting preparation, heat-treated ultralente) enabled the ARI to maintain a conduction velocity significantly greater than that seen in the rats given insulin alone. These results are suggested that the complexation of SER with the cyclodextrin derivative improves the pharmacological effect of sertraline, probably due to enhanced drug bioavailability. J.G. HYPOGLYCEMIC ACTIVITY OF PUTRANJIVA ROXBURGHII WALL. Although glomerular lesions in several animal models of diabetes are similar to those seen in diabetic nephropathy in humans, the time course of the development of the lesions is difficult to compare with that seen in human diabetes. In 1967 Chase and Tubbs reported that carnitine acyl transferase and hence fatty acid oxidation are inhibited by 2-bromostearate (see Ref. Olayaki and coauthors have investigated the effect of oral administration of methanol extracts of this plant on glucose tolerance, glycogen synthesis, and lipid metabolism in rats with alloxan-induced diabetes (Olayaki et al., 2015). The way in which the polyol pathway might act to cause the development of the conduction velocity deficit has received much attention in the past. Notably, alloxan is far less expensive and more readily available than streptozotocin. They demonstrated that Zn supplementation appeared to affect the early insulin response to glucose differentially among those with the rs13266634 genotype and that Zn supplementation could be beneficial for diabetes prevention and/or treatment for individuals based on the presence of the SLC30A8 variation. by Osasenaga Macdonald Ighodaro 1,2,*, Abiola Mohammed Adeosun 1,2 and Oluseyi Adeboye Akinloye 2. Alloxan diabetes and streptozotocin diabetes Figure 1 shows a schematic diagram of the tetraphasic and triphasic blood glucose responses induced by alloxan and streptozotocin, respectively, when injected [22]. At present the conditions required for development of human fetal or neonatal glucokinase have not been identified; but the same failure to accelerate glucose up take in the immediate postnatal period has been recorded (Section V, A). PHILLIP A. In conclusion, our results suggest that glycolytic metabolism and glucose uptake are altered in diabetic atherosclerosis. IN ALLOXAN INDUCED DIABETIC RATS HTML Full Text. Sertraline represents selective serotonin reuptake inhibitors, which lowered blood glucose level and is used in patients with diabetes to treat depression and improve glycemic control. CAD severity was assessed with … This reduction has been reported in numerous tissues, including erythrocyte32,43,100,111,201; liver8,111; retina and kidney43,100; and spleen, heart, testis, pancreas, and skeletal muscle in rats with streptozotocin and/or alloxan diabetes.8,43,100,111 The loss of SOD appears to be a function of duration and severity of diabetes.85,99, α-Tocopherol is reported to be reduced in streptozotocin diabetes.85,99 Our observations are that plasma α-tocopherol is very variable and is greatly dependent on dietary intake; it can be increased in experimental diabetes because of polyphagia.130, David M. Nathan, in Endocrinology (Sixth Edition), 2010. 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