Alex Ekwueme Federal University Ndufu Alike, Abakaliki, Nigeria
Question
Asked 23 October 2013
Can type 2 diabetes be induced by alloxan?
Any standard references.
Most recent answer
Alloxan, in combination with fructose can induce type 2 diabetes.
Popular answers (1)
East Suffolk and North Essex Foundation Trust
No! T2DM is a complex metabolic syndrome. Alloxan simply reproduces the beta cell loss and even then not the pathophysiological mechanisms of this beta cell loss which may be important as the abnormal fuel sensing may be part of the overall metabolic dysfunction. As in previous discussions of this topic I would encourage use of the description alloxan induced diabetes. I think this is more important for models of T2DM than such distinctions for models of T1DM as in T1DM the consequences of beta cell failure are simply that: consequences of beta cell failure with resulting hormone deficiency and hyperglycaemia. T2DM is far more complex. Sorry!!
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All Answers (30)
East Suffolk and North Essex Foundation Trust
No! T2DM is a complex metabolic syndrome. Alloxan simply reproduces the beta cell loss and even then not the pathophysiological mechanisms of this beta cell loss which may be important as the abnormal fuel sensing may be part of the overall metabolic dysfunction. As in previous discussions of this topic I would encourage use of the description alloxan induced diabetes. I think this is more important for models of T2DM than such distinctions for models of T1DM as in T1DM the consequences of beta cell failure are simply that: consequences of beta cell failure with resulting hormone deficiency and hyperglycaemia. T2DM is far more complex. Sorry!!
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Universitas Lambung Mangkurat of Banjarmasin Indonesia
Usually high fructose feeding rat used as T2DM animal model.
Alloxan and STZ used to induce T1DM base on their effect as low insulin production agent.
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Manchester Metropolitan University
Alloxan cannot be used to induce T2DM. Some available models include fructose-fed, high fat diet fed followed by a low dose of STZ and STZ/nicotinamide.
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Manchester Metropolitan University
IDDM in rodents, not in humans. Although no evidence on NIDDM (can't say no, but no evidence yet)
East Suffolk and North Essex Foundation Trust
But the point is alloxan alone will never reproduce the complex physiology of T2DM. The inclusion of other metabolic challenges eg fructose might go some way towards this? Good debate!
No, Type 2 DM is characterized by hyperglycemia due to decreased insulin release or insulin sensitivity due to partial damage of pancreatic beta cell, Alloxan causes complete destruction of pancreatic beta cell and thus causes type 1 diabetes. That's why Alloxan is used to induce type 1 diabetes. Streptozotocin when given with nicotinamide causes type 2 diabetes.
16. Shirwaikar A, Rajendran I and Punitha ISR. Antidiabetic activity of alcoholic stem extract of Coscinium fenestratum in streptozotocin-nicotinamide induced type 2 diabetic rats. J. Ethnopharmacol. 2005; 97:369-374.
Anwer T, Sharma M, Pillai KK and Iqbal M. Effect of Withania somnifera on insulin sensitivity in non-insulin dependent diabetes mellitus (NIDDM) rat. Basic Clin. Pharmacol Toxicol. 2008; 102: 498-503.
Tabriz University of Medical Sciences
I would suggest you to read the following articles:
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No, it can't.
Why ?
Alloxan is a well known diabetogenic agent widely used to induce T1DM in animals because it is a urea derivative which causes selective necrosis of the pancreatic islet beta cells ... with its reduction product dialuric acid establish a redox cycle with the formation of superoxide radicals. These radicals undergo dismutation to hydrogen peroxide. There after, highly reactive hydroxyl radicals are formed by fenton reaction. The action of reactive oxygen species (which DNA is one of their targets) with a simultaneous massive increase in cytosolic calcium concentration causes rapid destruction of beta cells.
So, beta cells damage lead to type I rather than type II diabetes mellitus.
Such information are necessary to know them .. You have to know all before inducing that type of diabetes, other information about Alloxan like the best method of preparation and its half-life and the sensitivity of rats into Alloxan which depends on the mode of administration, the speed of injection, their age, the diet ... are also important to put in mind.
Good luck.
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Banaras Hindu University
Please take a look at the following RG link and PDF attachment.
Thanks!
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University of Science and Technology
Many studies showed that alloxan can induce ROS, which is responsible for the destruction of B-cells, so as a result insulin- dependent diabetes mellitus or type IDM is formed.
Sher-i-Kashmir Institute of Medical Sciences
No. Alloxan has two distinct pathological effects; it selectively inhibits glucose induced insulin secretion through specific inhibition of glucokinase, the glucose
sensor of the beta cell, and it causes a state of insulin-dependent diabetes through its ability to induce ROS formation, resulting in the selective necrosis of beta cells.
The hyperglycemia-induced by alloxan is not sufficiently stable for proper evaluation of the antidiabetic or hypoglycemic potential of test compounds. Even in a few cases where apparent stability is achieved, the duration of such stable hyperglycemia is on average less than a month and this period is not adequate for proper evaluation of a test drug. This often leads to an elusive conclusion on the antidiabetic relevance of the test compound. A wide range of fluctuations in the blood glucose level and auto reversal from confirmed diabetic hyperglycemia to the non-diabetic range is a major setback as regards the alloxan-induced diabetes model. Another problem with alloxan is that its diabetogenic and toxic effects on animals vary widely, even among those belonging to the same species. Such inconsistent effect makes the drug an unreliable model for affirming the antidiabetic potency of test compounds. Moreover, alloxan does not exactly induce the human type 2 diabetes mellitus which accounts for about 90–95% of all diabetic cases. Alloxan has been noted to stimulate a type 1 form of diabetes when used in animals. This form of diabetes is often associated with high level of ketoacidosis that arguably is partly responsible for the high animal mortality rate (30–60%) usually observed with use of alloxan as a diabetogenic agent. Besides, the mechanism of alloxan diabetogenicity encloses a chronic measure of toxicity involving free radical generation, particularly (OH). No doubt, this play a bigger role in the mortality of experimental animals exposed to alloxan. Mortality from diabetes has been adduced to either initial hypoglycemic shock or emergence of diabetic complications or direct kidney tubular cell toxicity. The practice of placing alloxan-treated animals on 5–10% glucose solution in a bid to prevent hypoglycemic shock is often observed but this intervention appears not to be significantly helpful, and thus the problem of mortality persists. High mortality rate is a major drawback in the use of alloxan diabetic model. First, it increases the financial burden of the study as several animals more than required have to be used in attempt to carry the study to a meaningful end. Secondly, it does not allow for proper evaluation of the antidiabetic potential of the investigated compound or test drug.
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