Experimental diabetes mellitus. Alloxan Effects

Experimental diabetes mellitus can be obtained not only through pancreatectomy. For this purpose, alloxan, dehydroascorbic acid or dithizone can be used, each of which selectively causes b-cell necrosis at appropriate doses. Experimental diabetes can also be obtained using methods that cause the formation of antibodies, as well as by inbred breeding special lines of animals. There are also cytotoxins that destroy a-cells of islet tissue. These include cobalt chloride, guanidine derivatives (synthaline, phenylethyldiguanidine) and various hepatotoxins. Alloxan (a compound resulting from the oxidation of uric acid) has the remarkable property of causing selective necrosis of the islets of Langerhans without affecting the exocrine pancreatic tissue. The introduction of alloxan is accompanied by an increase in blood sugar, followed by temporary hypoglycemia, after which chronic hyperglycemia develops. The primary increase in blood sugar concentration is apparently associated with the direct effect of alloxan on liver tissue, while temporary hypoglycemia is due to insufficient glucose production by the liver cells. The development of chronic diabetes is a consequence of the destruction of b-cells of islet tissue. Thus, thanks to alloxan, we have a very convenient method for producing experimental diabetes without surgical removal of the pancreas, which is difficult to produce in many animal species. The mechanism of action of alloxan is unknown. It is a strong oxidizing agent that inactivates many enzyme systems. In addition to affecting the pancreas, alloxan causes the formation of cataracts, necrosis of the renal tubules and a number of less pronounced changes in the adrenal cortex, pituitary, thyroid and thymus. Large doses of alloxan are fatal, but the administration of about 300 mg per 1 kg of weight causes selective destruction of b-cells and only minimal damage to the tissue of the kidneys and other organs. Alloxan was less toxic to humans than to experimental animals. This was established when it was unsuccessfully tried to be used to combat malignant tumors of islet tissue. Even intravenous administration of 0.6-1 g of alloxan per 1 kg of weight did not cause the usual rapidly developing toxic effect. Experimental diabetes can also be obtained by the formation of antibodies to the own insulin of experimental animals. These antibodies are obtained by immunizing animals with insulin taken from other animals. So, in guinea pigs and rabbits, antibodies to pig and cattle insulin were obtained that inactivated the insulin of pigs and cattle. The immunological determination of insulin is also based on this method. With the introduction of such antibodies to mice, they may develop reversible diabetes. Another way to get diabetes is to use extracts of the anterior pituitary gland or purified growth hormone. In some animals, hormones of the adrenal cortex and thyroid gland are used for the same purpose. The most likely mechanism of action of all these substances is that they cause a steady increase in insulin secretion and, in the end, lead to the depletion of cells that produce this hormone. Long-term administration of glucose for most of the day, accompanied by an increase in blood sugar concentration, also causes diabetes. Some pets sometimes spontaneously develop a syndrome that resembles diabetes in humans. In mice, hereditary diabetes is described, accompanied by obesity and hyperglycemia, caused by a mutation of one of the genes. It is claimed that a similar hereditary disease occurs in hamsters (Cricetulus griseus).

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