It is known that the pathogenesis of type 2 diabetes in humans is based on two main factors – insulin resistance and inappropriate secretory activity of β-cells of the pancreas. In animals, the role of these mechanisms has not been clearly characterized, and the differences in the manifestations of experimental diabetes under the same conditions are not sufficiently substantiated. In order to study the prerequisites and mechanisms of the development of experimental type 2 diabetes or prediabetes under lipid overload, 6-month-old male Wistar rats were fed a high-fat diet for 4 weeks; after 2 weeks of the experiment, 20 or 25 mg/kg of streptozotocin was administrated. The development of insulin resistance was assessed using the insulin tolerance test. We evaluated the dynamics of glycemia in animals, subcellular signs of liver steatosis, and determined expression of the precursor and mature protein SREBP-1 by immunoblotting. It was found that in rats fed with a high-fat diet during the 2–4th weeks of the experiment, regardless of the administration of streptozotocin, stable insulin resistance and symptoms of prediabetes were detected. The severity of carbohydrate metabolism lesion, which appeared as type 2 diabetes or prediabetes after streptozotocin administration, depended on the level of hepatosteatosis due to high-fat diet, whereas the dose of streptozotocin influenced severity of type 2 diabetes. The use of a high-fat diet led to increased processing and activation of SREBP-1, which was clearly inhibited in type 2 diabetes. Therefore, the level of lipid infiltration of the liver and deregulation of the transcription factor SREBP-1 are risk factors defining development of type 2 diabetes or prediabetes in experimental rats with lipid overloading. Changes in the maturation of SREBP-1 with the use of a high-fat diet confirm that insulin resistance in rats revealed β-cell dysfunction, which closely approximates the mechanisms of experimental type 2 diabetes to main pathways in humans. At the same time, the predisposition to β-cell dysfunction can be a prerequisite that determines compensatory reserves for maintaining carbohydrate and lipid homeostasis under the influence of lipid load in both humans and laboratory animals.
In acute experiments on different age group of 30 white wild-type rats: juvenile (weight 130–175 g), mature (weight 200–250 g) and old (weight 300 g and more) we were investigated the changes in the volume rate of bile secretion with cyclooxygenase inhibition by acetylsalicylic acid (100 mkg/kg weight of animal) which is a blocker of the prostaglandin synthesis enzyme. We explored the changes of the level of choleresis and bile biochemical components by thin-layer chromatography In vivo. The relative abundances of cholecycle, henodeoxycholic, taurocholic and glycocholic bile acids in the liver of rats were determined by chromatography, with the subsequent densitometry. The biliary acid flow rate was calculated as the sum of the bile acid concentration multiplied by the volume of secreted biliary in one relevant thirty-minute sample. The conjugation coefficients were calculated for each thirty minute sample. Reduction of bile secretion by endogenous prostanoids was shown, because inhibition of prostaglandins synthesis caused the hypercholeresis on 42–112,5 % in different rat age groups, compared to control. Endogenous prostaglandins suppressed the processes of conjugation in old and juvenile age group on 117–189,1 %, in contrast these regulators have no significant effect on bile acids association with glycine and taurine in mature rats. The binding of endogenous prostanoids probably increased the conjugation processes in juvenile rats, whereas in the old experimental group acetylsalicylic acid was significantly reduced by 123 % on average. Analysis of changes in free and conjugated bile acids in the rats of different age groups showed that the ratio of qualitative changes in structure of the liver bile in rats with the cyclooxygenase blockade is mainly due to enhanced synthesis of free bile acids de novo. Therefore, endogenous prostanoids affect in the opposite way. There are have multi-directional impact on bile secretion in different age groups of rat that means ambiguous role of these drugs in liver function regulation at different stages of ontogenesis.
The studies were performed on male Wistar rats weighing 250-270 with experimental pneumonia (EP) induced by the method of A.M. Kulik. The animals were divided into the following groups: 1 – control; 2 - experimental pneumonia; 3 (first experimental group) - animals, which in parallel with the simulation of pneumonia were intraperitoneally administered uridine at a dose of 0.3 mg/100 g of body weight (daily within 1 week); 4 (second experimental group) - animals in which uridine was administered daily starting from day 4 (at the peak of pneumonia). Animals with EP were examined at 5th (n = 10), 9th (n = 8) and 12th (n = 6) days of the disease development, as well as 1 (n = 5) and 2 (n = 5) months after EP modeling. It was shown that in the first experimental group on the 5th day of EP development, an isoventilator restructuring of respiration was observed. In this group, from day 12 to the end of the study, there was a stenoventilator restructuring of breathing, which was characterized by an increase in tidal volume, alveolar ventilation, oxygen consumption and, accordingly, an increase in oxygen extraction from the alveoli and in the oxygen effect of the respiratory cycle. It can be assumed that in this group, an increase in the intensity of metabolism is provided by the effective activity of the respiratory system. In the second experimental group, isoventilator changes in respiration were observed with a gradual decrease in oxygen consumption and other indicators of the respiratory system efficiency. After 2 months, these changes became significant. Thus, we can talk about significant differences in the effect of uridine on the function of external respiration (i.e., apparently, on the activity of the mitochondrial ATP-dependent K+ channel) during EP, which depended on the period of onset of uridine administration. Application of uridine immediately (1st experimental group) looks more effective and even has a stimulating effect on the respiratory function over a long period of experiment. The administration of uridine starting from the 4 partially normalizes the respiration parameters. However, after 1 month there is a depression of the functions of the respiratory system, which, probably, may further worsen. The reasons for the differences in the identified dynamics require further investigation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.