Filters
The anti-diabetic potential of betaine. Mechanisms of action in rodent models of type 2 diabetes
The relevance of the heme oxygenase system in alleviating diabetes-related hormonal and metabolic disorders
Effects of Allyl Isothiocyanate on Oxidative and Inflammatory Stress in Type 2 Diabetic Rats
Oxidative stress and inflammation play a crucial role in the pathogenesis and progression of diabetes. Currently, there is a growing need to exploit plant-derived bioactive compounds to support conventional therapies. The purpose of this study was to explore allyl isothiocyanate (AITC) potency in reducing oxidative and inflammatory stress along with its profitable modulation trace element status in pathological conditions such as diabetes. Two weeks of oral AITC treatments (2.5, 5, and 25 mg/kg body weight per day) were evaluated in Wistar rats with diabetes induced by a high-fat diet and streptozotocin. The study included AITC influence on antioxidant factors (SOD, CAT, GST, Nrf2), stress and inflammatory markers (cortisol, CRP, IL-1β, IL-6, TNFα, NF-κB), lipid peroxidation indices (TBARS, -SH groups), and trace element status (Fe, Zn, and Cu) in the detoxification and lymphoid organs. Independently of dose, AITC increased cortisol levels in rat blood serum and decreased total thiol groups (T-SH) and protein-bound thiol groups (PB-SH) collaterally with raised thiobarbituric acid reactive substances (TBARS) in diabetic rat liver. The inflammation and oxidative effects were enhanced by an AITC dose increase. The highest dose of AITC, 25 mg/kg b.w., strongly affected the inflammation process by increasing IL-6, IL-1β, and TNFα in the blood serum, and it upregulated Nrf2 transcription factor with increased SOD, GPx, and GST activities in the liver. AITC showed an equivocal effect on profitable modulation of disturbances in mineral homeostasis in the liver, kidney, and spleen. Our findings revealed that two-week AITC treatment exacerbated oxidative and inflammation status in diabetic rats.
The Anti-Diabetic Potential of Baicalin: Evidence from Rodent Studies
Baicalin is a biologically active flavonoid compound that benefits the organism in various pathological conditions. Rodent studies have shown that this compound effectively alleviates diabetes-related disturbances in models of type 1 and type 2 diabetes. Baicalin supplementation limited hyperglycemia and improved insulin sensitivity. The anti-diabetic effects of baicalin covered the main insulin-sensitive tissues, i.e., the skeletal muscle, the adipose tissue, and the liver. In the muscle tissue, baicalin limited lipid accumulation and improved glucose transport. Baicalin therapy was associated with diminished adipose tissue content and increased mitochondrial biogenesis. Hepatic lipid accumulation and glucose output were also decreased as a result of baicalin supplementation. The molecular mechanism of the anti-diabetic action of this compound is pleiotropic and is associated with changes in the expression/action of pivotal enzymes and signaling molecules. Baicalin positively affected, among others, the tissue insulin receptor, glucose transporter, AMP-activated protein kinase, protein kinase B, carnitine palmitoyltransferase, acetyl-CoA carboxylase, and fatty acid synthase. Moreover, this compound ameliorated diabetes-related oxidative and inflammatory stress and reduced epigenetic modifications. Importantly, baicalin supplementation at the effective doses did not induce any side effects. Results of rodent studies imply that baicalin may be tested as an anti-diabetic agent in humans.
Differentiated Effects of Allyl Isothiocyanate in Diabetic Rats: From Toxic to Beneficial Action
Allyl isothiocyanate (AITC), a constituent of Brassica family plants, has been reported to possess a high bioactivity in animal and human cells, showing ambiguous properties from adverse to beneficial ones. It was reported its genotoxic, carcinogenic, goitrogenic effects. On the other side, AITC has shown anti-cancer, cardioprotective, neuroprotective, and lately anti-obesity abilities. So far, its anti-diabetic effects are poorly explored. We tried to assess AITC action on carbohydrate, lipid and hormonal disorders in high fat diet-fed/streptozotocin diabetic rats. In this report, diabetic rats were treated intragastrically at doses 2.5, 5 and 25 mg/kg b.w./day of AITC for 2 weeks. Irrespectively of doses, AITC considerably lowered thyroid hormones (fT4, fT3), increased liver TG content, and also caused robust LDL-cholesterol and direct bilirubin concentration enhancement. Moreover, AITC at the highest dose caused pancreatic amylase and lipase drops and thyroid gland hypertrophy. AITC at 2.5 and 5 mg significantly reduced blood glucose levels along with robust beta-hydroxybutyric acid drop. Additionally, AITC at 5 mg improved insulin sensitivity (HOMA-IR index) in spite of reduced blood insulin. To conclude, despite amelioration of diabetic hyperglycemia by AITC, the adverse lipids and hormonal effects may exclude its use as a health-promoting compound in terms of anti-diabetic properties.
Quercetin as an Anti-Diabetic Agent in Rodents—Is It Worth Testing in Humans?
Quercetin is a biologically active flavonoid compound that exerts numerous beneficial effects in humans and animals, including anti-diabetic activity. Its action has been explored in rodent models of type 1 and type 2 diabetes. It was revealed that quercetin mitigated diabetes-related hormonal and metabolic disorders and reduced oxidative and inflammatory stress. Its anti-diabetic effects were associated with advantageous changes in the relevant enzymes and signaling molecules. Quercetin positively affected, among others, superoxide dismutase, catalase, glutathione peroxidase, glucose transporter-2, glucokinase, glucose-6-phosphatase, glycogen phosphorylase, glycogen synthase, glycogen synthase kinase-3β, phosphoenolpyruvate carboxykinase, silent information regulator-1, sterol regulatory element-binding protein-1, insulin receptor substrate 1, phosphoinositide 3-kinase, and protein kinase B. The available data support the conclusion that the action of quercetin was pleiotropic since it alleviates a wide range of diabetes-related disorders. Moreover, no side effects were observed during treatment with quercetin in rodents. Given that human diabetes affects a large part of the population worldwide, the results of animal studies encourage clinical trials to evaluate the potential of quercetin as an adjunct to pharmacological therapies.
Regulatory Effects of Metformin, an Antidiabetic Biguanide Drug, on the Metabolism of Primary Rat Adipocytes
Metformin is a biguanide compound commonly applied in humans with type 2 diabetes. The drug affects different tissues, including fat tissue. The direct influence of metformin on cells of fat tissue, i.e., adipocytes, is poorly elucidated. In the present study, the short-term (4-h) effects of metformin on lipogenesis, glucose transport, lipolysis, and lactate release in primary rat adipocytes were explored. It was demonstrated that metformin reduced insulin-induced lipogenesis and increased glucose transport into adipocytes. The tested compound also decreased lactate release from fat cells. It was shown that metformin substantially limited lipolysis stimulated by epinephrine (adrenergic receptor agonist) and dibutyryl-cAMP (direct activator of protein kinase A). Moreover, metformin decreased the lipolytic process triggered by DPCPX (adenosine A1 receptor antagonist). In the case of each lipolytic stimulator, the drug evoked a similar inhibitory effect in the presence of 3 and 12 mM glucose. The lipolytic response of adipocytes to epinephrine was also found to be reduced by metformin when glucose was replaced by alanine. It was demonstrated that the tested compound limits the release of both glycerol and fatty acids from fat cells. The results of the present study provided evidence that metformin significantly affects the metabolism of primary rat adipocytes. Its action covers processes related to lipid accumulation and release and occurs after relatively short-term exposure.