Experimental Alloxan Diabetes Research Articles

The effect of phytoprotectors on the functioning of liver NAD⁺- and NADP⁺-maliс enzymes in rats with alloxan diabetes.

The development of experimental alloxan diabetes in rats was accompanied by the increase the activity of liver NAD⁺- and NADP⁺-dependent malic enzymes (ME; NAD⁺-ME, EC 1.1.1.39 and NADP⁺-ME, 1.1.1.40) associated with an increase in the rate of transcription of genes encoding these enzymes. Oral administration of aqueous extracts of Jerusalem artichoke and olive to diabetic rats caused a noticeable decrease in blood glucose, a decrease in the rate of transcription of the studied genes; and a decrease in ME activity towards normal values. Thus, extracts of Jerusalem artichoke and olive can be used as additives to the standard therapy of diabetes mellitus.

Molecular and biochemical studies of succinate dehydrogenase in rat liver under conditions of alloxan diabetes

Experimental alloxan diabetes in rats causes an increase in the activity of liver succinate dehydrogenase (SDH) without changes in its isozyme composition. The observed increase in the catalytic activity of SDH clearly correlates with the intensification of transcription of the genes encoding catalytic dimer of SDH. Analysis of the methyl status of the promoters of the genes, encoding the catalytic dimer of SDH in rats under normal and experimental conditions did not reveal any dependence on the level of their expression. The obtained results of bisulfite sequencing indicate a passive role of the epigenetic mechanism of regulation of SDH gene expression in the development of alloxan diabetes. The transcription factor CREB, responsible for of gluconeogenesis in diabetes, may play an important role in the control of the transcriptional activity of the sdha and sdhb genes.

The Effect of Ecdystene on the Activity of Matrix Metalloproteinases in Experimental Alloxan Diabetes in Rats

The Effect of Ecdystene on the Activity of Matrix Metalloproteinases in Experimental Alloxan Diabetes in Rats

Investigation of Antidiabetogenic Effect of the Iodine-Selenium Concentrate in Animals with Chronic Alloxan Diabetes of Varying Severity

BACKGROUND: The diabetogenic effect of alloxan is known is determined by ability to stimulate lipid peroxydation processes in B-cells of the pancreas.
 AIM: to investigate of the possible antidiabetic action of long time prolonged of Iodine-Selenium concentrate action in rats with alloxan diabetes.
 METHODS: Reproduction of experimental alloxan diabetes was carried out in rats by a single intravenous injection of alloxan 35-43 mg / kg body weight. The “iodine-selenium” concentrate was administered per os through a tube at the rate of 1.25 ml / 100 g of the concentrate. In experimental animals with mild and heavy diabetes mellitus, the level of glucose in the blood was assessed, products of LPO-AOD; the state of the histostructure of the pancreas and of insulin content in B cells were studied using of aldehyde fuchsin and diethylpseudoisocyanine methods.
 RESULTS: Long time prolonged administration of the “iodine-selenium” concentrate (60 days) to animals with mild experimental diabetes mellitus is accompanied by a significant decrease in blood glucose levels by 1.89 times compared to the control (p ˂ 0.05) and of LPO within normal values as by increase of the level of glutathione peroxidase (GPO) by 2.23 times compared with the initial (p˂ 0.01), by prevention of the development of histological changes in pancreatic islets and a slight decrease of insulin content in B-cells. Under similar experimental conditions in animals with severe alloxan diabetes, the level of glycemia significantly decreased from 20.23 ± 2.15 mmol / l to 12.39 ± 1.52 mmol / l as of the level of diene conjugates of erythrocytes and plasma, as decrease of ketodienes, MDA of plasma and in erythrocytes and primary lipid peroxidation products, while remaining elevated, despite an increase in GPO by 50.0% compared with control (p˂0.05) in the presence of histological changes in the pancreatic islets as in experimental diabetes.
 
 CONCLUSION: The antidiabetic effect of the “iodine-selenium” concentrate in rats with mild alloxan diabetes on the level of glycemia, LPO - AOD and state of the histostructure of the pancreas and the content of deposited insulin in pancreatic B-cells, is probably due to antioxidant effect of selenium to stimulate activity of glutathione blocking lipid peroxide and hydrogen peroxide in alloxan diabetes mellitus.

Comparative study of the neuroprotective activity of lithium compounds and their effect on the course of experimental alloxan diabetes mellitus in rats

A comparative study of the effects of an inorganic lithium salt (lithium carbonate) and an organic lithium salt (lithium ascorbate) on a model of alloxan diabetes mellitus was conducted. The use of lithium ascorbate for a month in experimental alloxan diabetes mellitus facilitates its course – the survival rate of animals increases, the level of glycemia decreases (especially when administered at a dose of 10 mg/kg). Morphometric analysis showed that lithium ascorbate in alloxan diabetes has a neuroprotective effect, which is manifested in a decrease in toxic damage to neurocytes with an increase in the number of cells with reversible changes and intact neurons. Lithium carbonate at doses of 5 and 10 mg / kg was not effective.

Effect of jerusalem artichoke extract on the functioning of malate dehydrogenase in the liver of rats with alloxan diabetes

An increase in the activity and the appearance of a new isoform of NAD-dependent malate dehydrogenase (MDH; EC 1.1.1.37) has been detected in the liver of rats with alloxan diabetes was revealed. This confirms the possibility of MDH involvement in the adaptive reaction of the body under oxidative tress caused by biochemical changes in diabetic animals. The increase in the hepatic MDH activity in rats with experimental type I diabetes mellitus (T1DM) is associated with the formation of an additional MDH isoform in peroxisomes. Data on the expression of the MDH encoding genes mdh1 and mdh2 confirm that in T1DM the increase in MDH activity occurs at the level of transcription of MDH encoding genes. The use of the extract of Helianthus tuberosus led to a marked decrease in the blood glucose concentration of rats with alloxan diabetes, abolished by the change in transcriptional activity of the studied genes and blocked the formation of new MDH isoforms in rats with experimental alloxan diabetes. This suggest that extract of H. tuberosus may be of considerable interest from the point of view of pharmacological correction of metabolic changes during the development of pathologies of this kind.

Парадоксальная рефрактерность, возникающая при аллогенном переносе животным с аллоксановым диабетом суммарной РНК лимфоцитов селезенки вылеченных особей

Ранее нами было показано, что препараты аллогенной суммарной РНК, выделенной из лимфоидных и стволовых клеток здоровых животных, вызывают нормализацию уровня глюкозы крови у крыс со стойким аллоксановым сахарным диабетом. Цель исследования -- выяснение влияния суммарной РНК лимфоцитов селезенки крыс, ранее перенесших стойкий аллоксановый диабет, на особенности течения эксперименального аллоксанового диабета у животных. Методика. Эксперимент выполнен на 35 белых беспородных крысах-самках массой 250-280 г: 5 интактных животных, 20 - с экспериментальным аллоксановым сахарным диабетом и 10 животных, ранее перенесших стойкий аллоксановый диабет, у которых уровень глюкозы крови был полностью нормализован введением суммарных РНК клеток костного мозга, селезенки и поджелудочной железы. Диабет у этих животных моделировали однократным подкожным введением полного адъюванта Фрейнда (0,5 мл на крысу) и последующим подкожным введением аллоксана тригидрата в дозе 200 мг/кг. Достигнутая нормогликемия у животных подтверждалась в течение последующих 60 сут. Из селезенок и костного мозга этих животных методом фенол-хлороформной экстракции была выделена суммарная РНК. На 20 крысах с экспериментальным аллоксановым сахарным диабетом изучали эффекты однократного внутрибрюшинного введения полученной суммарной РНК (15 мкг/100 г массы тела животного). Результаты. Обнаружено, что при введении суммарной РНК селезенки крыс, ранее перенесших аллоксановый диабет, животным с аллоксановым диабетом у последних развивалась стойкая и длительная рефрактерность к лечению терапевтическими препаратами РНК. Заключение. 1. Выявлен феномен повышенной чувствительности крыс с аллоксановым диабетом к действию суммарной РНК селезенки животных, ранее перенесших аллоксановый диабет. 2. Предполагаемой причиной рефрактерности является клональный компонент суммарной РНК CD8+ Т-лимфоцитов памяти из селезенки животных, ранее перенесших аллоксановый диабет. 3. Предполагается наличие механизма адресного взаимодействия отдельных компонентов суммарной РНК селезенки крыс, ранее перенесших аллоксановый диабет, с их лимфоцитами-мишенями в организме реципиентов с аллоксановым диабетом. Introduction. Earlier we have shown that preparations of allogenic total RNA from lymphoid and stem cells of healthy animals contribute to normalization of blood glucose levels in white outbred rats with persistent alloxan-induced diabetes mellitus. The aim of this study was to find out whether allogenic total RNA isolated from the spleen of rats treated for alloxan diabetes affects its course, as determined by changes in blood glucose, in animals with persistent alloxan diabetes. Methods. Experiments were performed on 35 white outbred female rats weighing 250-280 g. Rats were divided into intact animals (n=5), rats with experimental alloxan diabetes mellitus (n=20), and rats after persistent alloxan diabetes (n=10) whose blood glucose level had been completely normalized by administrating total RNA of bone marrow, splenic, and pancreatic cells (post-diabetes group). Diabetes mellitus was modeled with a single subcutaneous (s.c.) injection of complete Freund’s adjuvant (0.5 ml) followed by a s.c. injection of alloxan trihydrate (200 mg/kg). Achievement of normoglycemia in animals of the post-diabetes group was confirmed over the next 60 days. Then total RNA was isolated from their spleen and bone marrow by phenol-chloroform extraction, and the effect of a single intraperitoneal injection of total RNA (15 μg/100 g body weight) was studied. Results. Administration of splenic total RNA from rats previously treated for alloxan diabetes to animals with alloxan diabetes resulted in development of stable and prolonged refractoriness of diabetic rats to the treatment with therapeutic RNA preparations [11]. Conclusions. This study discovered a phenomenon of hypersensitivity of rats with alloxan diabetes to the diabetogenic effect of total RNA from animals that had previously had alloxan diabetes. Apparently, this refractoriness was caused by the clonal component of the total RNA of CD8 + T memory lymphocytes from the spleen of post-diabetes animals. A mechanism is proposed for the interaction between individual components of splenic total RNA from post-diabetes rats and their target lymphocytes in recipients with alloxan diabetes.

О феномене повышенной чувствительности крыс, ранее перенесших аллоксановый диабет, к диабетогенному воздействию суммарной РНК

Введение. Как было нами показано ранее, препараты аллогенных суммарных РНК лимфоидных и стволовых клеток способствуют нормализации уровня глюкозы в крови белых беспородных крыс со стойким аллоксановым диабетом. Цель исследования - оценка влияния суммарной РНК, выделенной из селезенки крыс с аллоксановым диабетом, на уровень глюкозы в крови интактных крыс и животных, перенесших стойкий аллоксановый диабет. Методика. Эксперимент выполнен на 34 белых беспородных крысах-самках массой 250-280 г.: 12 интактных животных составили «интактный контроль». У 22 животных моделировали аллоксановый диабет путем однократного подкожного (п/к) введения полного адъюванта Фрейнда (0,5 мл) и последующего подкожного введения аллоксана тригидрата (200 мг/кг) - группа «алоксановый диабет». Селезенка 10 крыс группы «аллоксановый диабет» была использована для получения суммарной РНК. У 12 крыс группы «аллоксановый диабет» уровень глюкозы в крови был стабильно нормализован введением суммарной РНК клеток костного мозга, селезенки и поджелудочной железы - группа «перенесшая диабет». На 45-е сут эксперимента 12 крыс группы «интактный контроль» и 12 крыс группы «перенесшей диабет» использованы в новом опыте (по протоколу «2-й этап работы»). У 6 животных группы «интактный контроль» (впервые) и у 6 животных группы «перенесший диабет» (повторно) моделировали аллоксановый диабет путем подкожного введения аллоксана в дозе 100 мг/кг. Оставшимся 6-ти животным группы «интактный контроль» и 6-ти животным группы «перенесших диабет» вводили внутрибрюшинно суммарную РНК (15 мкг/100 г веса тела), выделенную из селезенок 10 крыс группы «аллоксановый диабет. Результаты. Показано, что исследуемая суммарная РНК в дозе 15 мкг/100 г массы тела вызывала гипергликемию у всех подопытных животных, сравнимую с действием 600-700-кратной дозы самого аллоксана, при этом крысы, ранее перенесшие диабет, реагировали значимо сильнее. Повторный контакт с аллоксаном у крыс, перенесших ранее диабет, так же вызывал значимо более выраженную гипергликемию, чем реакция на аллоксан у интактных крыс. Заключение. Выявлен феномен диабетогенного действия исследуемой суммарной РНК, а также повышенную чувствительность животных, ранее перенесших аллоксановый диабет, к повторному действию повреждающего агента. Полученные эффекты свидетельствуют о принципиальной возможности использовать суммарную РНК лимфоидных клеток для создания моделей заболеваний человека и разработку новых подходов в области персонифицированной медицины. Introduction. As we have shown earlier, preparations of allogenic total RNA from lymphoid and stem cells contribute to normalization of blood glucose levels in white outbred rats with persistent alloxan-induced diabetes. The aim of this study was to evaluate the effect of total RNA from the spleen of rats with alloxan diabetes on blood glucose of intact and post-alloxan diabetic animals. Method. Experiments were performed on 34 white outbred female rats weighing 250-280 g. Rats were divided into intact animals (n=12) and rats with experimental alloxan diabetes mellitus (n=22). Diabetes mellitus was modeled by a single subcutaneous (s.c.) injection of complete Freund’s adjuvant (0.5 ml) followed by a s.c. injection of alloxan trihydrate (200 mg/kg). Spleens from 10 rats with alloxan diabetes were used for obtaining total RNA. In the remaining 12 rats with alloxan diabetes, the level of blood glucose was completely normalized by administration of total RNA from the bone marrow, spleen, and pancreas (post-diabetes group). On day 45 of this experiment, 12 intact rats and 12 post-diabetes rats were used for a new experiment (second stage protocol). Alloxan diabetes was induced in 6 intact rats (for the first time) and 6 post-diabetes rats (for the second time) by a s.c injection of alloxan 100 mg/kg. The remaining 6 rats of the intact control group and 6 rats of the post-diabetes group received an injection of total RNA (15 μg/100 g body weight, i.p.). Results. Administration of total RNA (15 μg/100 g body weight) induced hyperglycemia in all experimental animals, which was comparable with the effect of a 600-700-fold dose of alloxan. Rats that had previously had diabetes responded to the total RNA significantly stronger. Likewise, a repeated exposure to alloxan of post-diabetes rats induced significantly more pronounced hyperglycemia than the response to alloxan of intact rats. Conclusions. This study discovered a phenomenon of hypersensitivity to repeated exposure to alloxan and to the diabetogenic effect of total RNA in animals that had previously had alloxan diabetes. This effect suggests a possibility of using the total RNA of lymphoid cells to create animal models of human diseases and to develop new approaches in personalized medicine.

Роль суммарных РНК лимфоидных и стволовых клеток в коррекции уровня глюкозы в крови при экспериментальном сахарном диабете

Цель - оценка влияния препаратов суммарной РНК лимфоидных клеток на уровень глюкозы в крови при экспериментальном аллоксановом диабете. Методика. Работа выполнена на 68 белых беспородных крысах обоего пола массой 180-220 г. Для моделирования аллоксанового сахарного диабета 1 типа животным однократно подкожно вводили полный адъювант Фрейнда в дозе 0,5 мл/крысу. Через 24 ч (на фоне 24-часового голодания, при свободном доступе к воде) однократно подкожно вводили препарат аллоксан тригидрат («La Chema», Чехия) в дозе 200 мг/кг (4% раствор в 0,9% NaCl). Для предотвращения фатального кетоацидоза, начиная с 3-х сут после введения аллоксана, все крысы получали базисную инсулинотерапию. В экспериментах использовано 8 разновидностей препаратов суммарной РНК: из лимфоидных клеток селезенки, из костного мозга и хвостовой части поджелудочной железы интактных крыс (РНКс-1, РНКкм-1 и РНКп/ж, соответственно); из лимфоидных клеток селезенки крыс, подвергнутых кровопусканию в объеме 2% от массы тела за 17 ч до выделения РНК (РНКс-2 с индуцированной повышенной морфогенетической активностью); из лимфоидных клеток селезенки и тимуса крыс, подвергнутых кровопусканию в объеме 2% от массы тела за 96 ч до выделения РНК (РНКс-3 и РНКт-3, соответственно, с высокой ингибирующей морфогенез активностью); из лимфоцитов периферической крови здорового человека (РНКлпкч), а также из стволовых клеток стромы пупочного канатика человека. Результаты. Показана возможность восстановления функции инсулярного аппарата и стойкой нормализации уровня глюкозы в крови крыс с экспериментальным аллоксановым диабетом 1 типа. Установлено наличие корригирующей способности аллогенных и ксеногенных препаратов суммарной РНК, выделенной из лимфоидных органов крыс и лимфоцитов периферической крови человека, а также из мезенхимных стромальных клеток пуповины человека, в отношении уровня глюкозы крови у крыс. Продемонстрирован различный вклад препаратов суммарной РНК, полученной из разных лимфоидных органов и стволовых клеток, в восстановлении нормального уровня глюкозы в крови животных. Установлено, что указанные препараты действуют на разные ткани-мишени в процессе восстановления функции инсулярного аппарата. Заключение. Полученные данные свидетельствуют о принципиальной возможности эффективного лечения сахарного диабета 1 и 2 типов. Доказана эффективность неинвазивного интраназального введения аллогенных и ксеногенных препаратов суммарной РНК лимфоидных и стволовых клеток. Полученные результаты ставят вопрос о необходимости разработки более адекватной экспериментальной модели, а также о перспективности поиска подходов к персонифицированному индивидуальному лечению этой патологии с учетом особенностей ее развития в каждом конкретном случае. Aim. To study the effect of total RNA from lymphoid cells on blood glucose in experimental alloxan diabetes mellitus (DM). Methods. The study was conducted on 68 white mongrel rats of both sexes weighing 180-220 g. Alloxan DM was modeled with full Freund’s adjuvant (0.5 ml/rat). After 24 h of fasting with free access to water, a single dose of alloxan trihydrate (La Chemas, Czeck Republic) was injected subcutaneously (200 mg/kg as a 4% solution in saline). All rats received basis insulin therapy starting from day 3 of the alloxan injection to prevent fatal ketoacidosis. Eight types of total RNA were used: from splenic lymphoid cells, bone marrow, and caudal part of the pancreas of intact rats; from splenic lymphoid cells of rats after blood withdrawal (2% of body weight 17 h prior to RNA isolation) (RNA after induction of increased morphogenetic activity); from splenic and thymic lymphoid cells of rats after blood withdrawal (2% of body weight 96 h prior to RNA isolation) (RNAs with high morphogenesis-inhibiting activity); and from peripheral blood lymphocytes and umbilical cord stromal stem cells of a healthy human. Results. The study showed a possibility for functional recovery of the insular apparatus and stable normalization of blood glucose level in rats with experimental alloxan DM, a model of clinical type 1 DM. Allogenic and xenogeneic total RNAs isolated from rat lymphoid organs, peripheral blood lymphocytes, and mesenchymal stromal cells of human umbilical cord were able to correct the blood glucose level in rats. Total RNAs isolated from different lymphoid organs and stem cells differently contributed to normalization of blood glucose in rats. These total RNAs were shown to influence different target tissues during restoration of the insular apparatus function. Conclusion. The study showed a principle possibility of effective therapy for types 1 and 2 DM and demonstrated the efficacy of non-invasive intranasal administration of allogenic and xenogeneic total RNAs from lymphoid and stem cells. These results indicated a need for developing a more relevant experimental model and offered a promising outlook for individualized treatment of this disease with due account of its peculiar features in each specific case. The study was conducted as a part of the Program for Basic Research of State Academies of Science in 2013-2020 on Development of Cell Models for Molecular Processes in Organs and Tissue (V.N. Orekhovich Research Institute of Biomedical Chemistry) and the complex Research Work #01201354257 on Regulation of Hemopoietic and Nonhemopoietic Functions of Bone Marrow Cells in Experiment and Clinic (Sounth Ural State Medical University).

The metabolic correction of the experimental alloxan diabetes by means of the antioxidant remedies

The research concerning the effect of the remedies with the different antioxidant mechanisms on the indices of carbohydrate and lipid metabolism as well as the thiol link of the antioxidant system and the functional detoxication system in modeling conditions of the decompensated alloxan diabetes mellitus have been presented. The research was performed on 105 white nonlinear male-rats with initial body weight (b.w.) 200-230 g, divided into seven groups. Group 1 has consisted of the intact animals. Group 2 (the comparison group) has consisted of the animals suffering from the severe alloxan diabetes mellitus (intraperitoneal administration of alloxan monohydrate at 10 mg/100 g b.w. three times, with an interval of one day, against fasting) without correction. In groups 3-7 diabetes mellitus has also been modeled. The animals of group 3 were fed by the diet with the supplement containing the antioxidant complex with high content of carotenoid substances (1 mg lutein per day, orally for a month before simulations of diabetes mellitus and for a month after). The animals of group 4 have been given the sodium dichloroacetate (15 mg/100g bw) with drinking water for the month before and a month after the modeling of diabetes. The animals of group 5 have been injected with the reduced glutathione (15 mg/100 g of b.w.) daily one week prior to administration of alloxan and until the end of the experiment, the animals of group 6 have been injected with the quercithin (10 mg/100 g of b.w.) and the rats of group 7 have been given the water with the reduced content of deuterium (91 mg/l) instead of the usual drinking water. The development of experimental alloxan diabetes mellitus in rats has been accompanied by the increase in blood plasma of glucose concentration by 6.9-fold, cholesterol and lipoproteins of low density by 66 and 100% respectively. The compensatory activity increase of the antiradical protective enzymes (glutathione peroxidase and glutathione reductase) as well as the concentration decrease of reduced glutathione in erythrocytes by 11% have been revealed. According to the data concerning the level of the molecules with medium and low mass in blood plasma as well as in erythrocytes, the evident endogenous intoxication has taken place. The performed researches have proved the presence of the significant hypoglycemic effect of the usage of sodium dichloroacetate, of the water with the reduced content of deuterium and of quercithin - the glucose concentration in these groups was lower than in the comparison group by 36, 33 and 47% respectively. In the same groups as well as in the group of rats injected with glutathione the hypolipidemic effect of various manifestation degree has been detected, the most evident in animals from group 7 in which all the indices except triglycerides haven't differed from indices of the control group. The usage of various corrective methods has also assisted the adequate functioning of the antioxidant system that has been proved by the normalization of glutathione content except of groups 3 and 6 in which its concentration was lower than the control indices by 25 and 12% respectively. Endogenous intoxication has been significantly lower in groups 4, 5 and 7 in which the level of molecular of medium and low mass in blood plasma was normal and only in erythrocyte mass was increased by 49-74% than in the control group. Thus, the data obtained prove the usage availability of the antioxidant remedies in the complex therapy in patients suffering from the diabetes mellitus. The most interesting is the usage of antioxidants with the indirect mechanism of action, i.e. the water with the reduced content of deuterium and sodium dichloroacetate. Quercithin and the reduced glutathione deserve attention as well, and considering the hypoglycemic effect of the first one and the metabolic effects of glutathione aimed at the functioning maintenance of the non-specific organism resistance, the possibility of the combined usage of both antioxidants should be taken into account.

Transcranial electrostimulation activates reparative regeneration and the insulin-producing function of pancreatic B-cells in alloxan diabetes in rats

Studies on rats with experimental diabetes induced by administration of alloxan showed that transcranial electrostimulation of endorphinergic brain structures stimulates the regeneration of damaged beta-cells in pancreatic islets of Langerhans. This was identified on pancreatic sections stained with hematoxylin and eosin. De novo formation of small islets was noted, as evidenced by their regeneration from progenitor cells. After transcranial electrostimulation, islet beta-cells stained by the Gomori method showed recovery of granularity - a sign of insulin production. Application of an immunoenzyme method demonstrated recovery of blood insulin levels, the dynamics of increases in which showed a highly significant negative correlation with a decrease in blood glucose. These data led to the conclusion that the antihyperglycemic effect of transcranial electrostimulation in experimental alloxan diabetes results from reparative regeneration of beta-cells in islets of Langerhans with recovery of their insulin-producing function.

Effect of the Heparin–Lysine Complex on the Hemostatic and Insular Systems

We studied the effect of chronic intraperitoneal administration of heparin-lysine complex on the state of the hemostatic and insular systems in young and senescent animals (rats). This complex exerted a positive effect on physiological function of the coagulant, anticoagulant, and fibrinolytic components of the hemostatic system in the norm and in developing experimental alloxan diabetes. In this case, both the complex and its components, lysine and heparin, had a pronounced antidiabetogenic effect.

Blood rheology in experimental diabetes mellitus

Electrical break-down and erythrocyte membrane potential and blood viscosity and elasticity were studied on the model of experimental alloxan diabetes on days 7 and 14 of the experiment. Changed membrane elasticity was revealed in both terms, more evident changes in the second term, on day 14. Increased membrane electrical break-down and decreased potential were noted. Impairments of blood viscosity and elasticity are caused by changed membrane electrical properties. Increasing capillary pressure, these changes lead to an increase of microvessel walls permeability. S. This, alongside with the tissue hypoxia developing in diabetes, stimulates plasmatic saturation of basal membrane and proliferation of vascular endothelium.

Homeostatic role of anticalcitonin antibodies in calcium metabolism in experimental diabetes mellitus

In experimental alloxan diabetes marked hypocalcemia and hyperglycemia are observed in the blood of rats during the acute period of the disease (from 1.5 to 2 months). After 2.5-3.5 months of diabetes calcium level reaches the upper normal limit. Simultaneously, antibodies to calcitonin appear. It is quite likely that excessive calcitonin secretion, leading to hypocalcemia, decreased insulin secretion and hyperglycemia take place in the acute stage of diabetes. When diabetes persists the antibodies to calcitonin which reveal a homeostatic reaction blocking the excess of calcitonin appear. This normalizes the level of calcium in the blood and prevents the further increase in the blood sugar level.

Effect of oral insulin administration in liposomes on some indices of carbohydrate and pigment metabolism during experimental mechanical jaundice and alloxan diabetes mellitus

Effect of oral insulin administration in liposomes on some indices of carbohydrate and pigment metabolism during experimental mechanical jaundice and alloxan diabetes mellitus

Topography of subnuclei of the hypothalamic paraventricular nucleus in rats and sensitivity of their neurons to insulin deficiency

This investigation was undertaken to study the reaction of paraventricular nuclei (PVN) subnuclei to insulin deficiency and to elevation of the blood glucose level under conditions of experimental alloxan diabetes. Experiments were carried out on 15 control and 15 experimental mature male Wistar rats. The state of the carbohydrate metabolism of the diabetic and control animals was judged by the blood glucose and radioimmune insulin levels. The results of these investigations show that both magnocellular and parvocellular neurons of PVN react to alloxan diabetes, which supports the hypothesis that PVN of the hypothalamus participates in the control of carbohydrate metabolism.

Electronmicroscopic cytochemical studies on lysosomes and peroxisomes of a rat cardiac muscle in the experimental alloxan diabetes

The combined electronmicroscopic and cytochemical investigations of lysosomes and peroxisomes of a rat cardiac muscle were carried out in various duration time of the alloxan diabetes. The analysis of cytochemical reactions with DAB, confirming the existence of peroxisomes in rat heart muscle revealed that the state of experimental alloxan diabetes did not at all affect either cytochemical or morphological image of peroxisomes. In comparison with the control group, in all 3 experimental groups cytochemical reaction to acid phosphatase markedly pointed to the increase in number and size of electron-dense bodies (lysosomes) with positive reaction. This state may most probably result both from local and general organism disturbances in metabolism, induced by particular experimental conditions.

Some histochemical observations on the myocardial metabolism in experimental conditions: Part I

In the paper the author is concerned with the histochemical estimation of the metabolic adaptation of the heart muscle of albino rats during an early experimental alloxan diabetes. It has been found that the state of experimentally produced insulin deficiency directly influences metabolism of the heart muscle and the changes observed in the histochemical reactions prove this. An increase in the intensity of histochemical reactions concerns the PAS-positive reaction and the reactions to the NADH and NADPH tetrazole reductase activities. Alkaline phosphatase shows a decrease in the enzymatic activity, whose nature is transitional and reversible with regard to cytochrome oxidase and ATP-ase. The histochemical picture of metabolic changes depends on the duration time of experimental diabetes.

Some histochemical observations on the myocardial metabolism in experimental conditions: Part II

A histochemical evaluation of the activity of chosen oxido-reductive enzymes of the cardiac muscle connected with the citric acid cycle, glycolysis and pentose shunt in the early experimental alloxan diabetes period in white rats has been carried out. Dehydrogenases: succinate, isocitrate and glucose-6-phosphate indicated a decrease in the enzymatic activity while the lactate dehydrogenase activity did not undergo any change. An increase in the intensity of the histoenzymatic reaction only concerned glutamate dehydrogenase. The presented histoenzymatic evidence of changes in the enzymatic activities may speak for the possibility of an existence of a direct diabetes influence on the cardiac muscle metabolism.

Sensitivity of the central nuclei of the vagus nerve to insulin deficiency in rats (Enzyme-histochemical study)

The distribution and activity of acetylcholinesterase (AChE) in the central nuclei of the vagus nerve (nucleus dorsalis and nucleus ambiguus) were investigated by Gomori's (1952) histochemical method in sexually mature male rats, intact or with experimental alloxan diabetes. The number of cells with high AChE activity in nucleus dorsalis was increased by 6% in the rats with alloxan diabetes. The results suggest a role of the dorsal nucleus of the vagus nerve in the regulation of pancreatic endocrine function.