Archives of Physiology and Biochemistry最新文献

A significant increase in the worldwide incidence and prevalence of type 2 diabetic mellitus (T2DM) has elevated the need for studies on novel and effective therapeutic strategies. Sirtuin 1 (SIRT1) is an NAD + dependent protein deacetylase with a critical function in the regulation of glucose/lipid metabolism, insulin resistance, inflammation, oxidative stress, and mitochondrial function. SIRT1 is also involved in the regulation of insulin secretion from pancreatic β-cells and protecting these cells from inflammation and oxidative stress-mediated tissue damages. In this regard, major SIRT1 activators have been demonstrated to exert a beneficial impact in reversing T2DM-related complications including cardiomyopathy, nephropathy, retinopathy, and neuropathy, hence treating T2DM. Therefore, an accumulating number of recent studies have investigated the efficacy of targeting SIRT1 as a therapeutic strategy in T2DM. In this review we aimed to discuss the current understanding of the physiological and biological roles of SIRT1, then its implication in the pathogenesis of T2DM, and the therapeutic potential of SIRT1 in combating T2DM.

Context: Inflammatory and immune pathways play a crucial role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Sitagliptin blocks the dipeptidyl peptidase-4 (DPP-4) enzyme, mechanisms that alter inflammatory pathways and the innate immune system, and by which Sitagliptin affects the pathogenesis of NAFLD weren't previously discussed.

Objective: This study aims to understand the interaction between Sitagliptin and innate immune response in order to meliorate NAFLD.

Methods: Thirty- two Wistar male albino rats were categorised into four groups. Rats have received a standard diet or a high-fat diet either with or without Sitagliptin. Serum HMGB1, protein and mRNA expressions of hepatic TLR4 and NF-κB, inflammatory cytokines, and histopathological changes were analysed.

Results: An ameliorative action of Sitagliptin in NAFLD was demonstrated via decreasing HMGB1-mediated TLR4/NF-κB signalling in order to suppress inflammation and reduce insulin resistance.

Conclusion: Sitagliptin may in fact prove to be a beneficial therapeutic intervention in NAFLD.

This study aimed to evaluate the therapeutic role of erythropoietin (EPO) or myoinositol versus metformin (MET) in improving the reproductive functions and glucose tolerance in a rat model of polycystic ovary (PCOS). Oral letrozole (LTZ) was used for induction of PCOS in wester rats for 21 days, after that, MET, EPO and myoinositol were administered for the following 21 days. The LTZ-induced PCOS rats have lost their oestrous cyclicity and become fixed at the diestrus phase, developed insulin resistance, abnormal sex and gonadotrophin hormone serum levels, increased cystic follicles, decreased number of the growing follicles and very little or no corpora lutea on microscopic examination, which were reversed by the three drugs, MET, EPO and myoinositol. MET and myoinositol were mostly equally effective in improving the reproductive manifestations of the disease. However, EPO was most effective in decreasing the insulin level observed in this LTZ-induced model of PCOS.

The current research was aimed to evaluate the antidiabetic activity of Terminalia citrina methanolic extract (TCME) by streptozotocin-induced diabetes in male Wistar rats. TCME exhibited better in-vitro antioxidant and alpha-amylase inhibitory activity as compared to other tested extracts. TCME at 250, 500, and 750 mg/kg showed notable (p < .05) antidiabetic potential by lowering fasting blood glucose level, restoring lipid level, serum amylase, HbA1c, kidney, and liver function tests as coevidenced from histological findings of the liver, pancreas, and kidney. TCME remarkably reinstated the antioxidant enzymatic activities (CAT: 0.181 ± 0.011 IU/mg protein, SOD: 21.45 ± 1.53 IU/mg protein) and reduced lipid peroxidation level (40.60 ± 2.41 µM/mg protein) in the liver and kidney tissue of diabetic rats at 750 mg/kg dose. The acute and subacute oral toxicity study of TCME exhibited no clinical toxicity signs and mortality. Its GC-MS spectrum unveiled the existence of 10-octadecenoic acid and other compounds which might have contributed to antidiabetic potential.

Hydrogen sulphide (H₂S), a newly identified gasotransmitter, can be endogenously produced by cystathionine gamma-lyase (CSE) in the cardiovascular system. This study investigated the role of the CSE/H₂S system on lipid overload-induced lipotoxicity and cardiac senescence. Lipid overload in rat cardiomyocyte cells (H9C2) promoted intracellular accumulation of lipid, oxidative stress, mitochondrial dysfunctions, lipid peroxidation and inhibited cell viability, all of which could be reversed by exogenously applied H₂S. Further data revealed that H₂S protected H9C2 cells from lipid overload-induced senescence by altering the expressions of lipid metabolism-related genes and inhibiting cellular acetyl-CoA and global protein acetylation. Enhancement of protein acetylation abolished the protective role of H₂S on cardiac senescence. In vivo, knockout of the CSE gene strengthened cardiac lipid accumulation, protein acetylation, and cellular ageing in high fat diet-fed mice. Taken together, the CSE/H₂S system is capable of maintaining lipid homeostasis and cellular senescence in heart cells under lipid overload.

Context: Obesity-associated chronic metabolic disease is a leading contributor to mortality globally. Plants belonging to the genera Acacia are routinely used for the treatment of diverse metabolic diseases under different ethnomedicinal practices around the globe.

Objective: The current review centres around the pharmacological evidence of intestinal-level mechanisms for metabolic health benefits by Acacia spp.

Results: Acacia spp. increase the proportions of gut commensals (Bifidobacterium and Lactobacillus) and reduces the population of opportunistic pathobionts (Escherichia coli and Clostridium). Acacia gum that is rich in fibre, can also be a source of prebiotics to improve gut health. The intestinal-level anti-inflammatory activities of Acacia are likely to contribute to improvements in gut barrier function that would prevent gut-to-systemic endotoxin translocation and limit "low-grade" inflammation associated with metabolic diseases.

Conclusion: This comprehensive review for the first time has emphasised the intestinal-level benefits of Acacia spp. which could be instrumental in limiting the burden of metabolic disease.

Objective: Diabetic cardiomyopathy is one of the most common complications of diabetes. Escin may significantly inhibit myocardial damage through its NF-κβ inhibitory, antidiabetic, neuroprotective, and potent anti-inflammatory activity. Hence, the study was carried out to evaluate the effect of escin in diabetic cardiomyopathy.

Methods: Diabetes induction was done in rats with streptozotocin. After six weeks of induction, diabetic animals were administered with escin (5, 10, and 20 mg/kg) for the next four weeks.

Results: Escin prevented the progression of abnormalities in the biochemical, hemodynamic parameters and electrocardiogram. Escin also prevented the progression of abnormality in the oxidative stress parameters. The expression of NF-κβ and MCP-1 was significantly reduced with escin treatment. Furthermore, escin also prevented damage to myocardial cells and reduced collagen deposition in the cardiomyocytes.

Conclusion: Escin prevented the progression of cardiomyopathy in diabetic rats. Hence escin can be an alternative option for the management of diabetic cardiomyopathy.

Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are common causes of chronic liver disease that share the range of steatosis, steatohepatitis, fibrosis, cirrhosis, and finally, hepatocellular carcinoma. They are identified by the dysregulation of disease-specific signalling pathways and unique microRNAs. Capsaicin is an active ingredient of chilli pepper that acts as an agonist of transient receptor potential vanilloid subfamily 1. It seems that the protective role of capsaicin against NAFLD and ALD is linked to its anti-steatotic, antioxidant, anti-inflammatory, and anti-fibrotic effects. Capsaicin-induced inhibiting metabolic syndrome and gut dysbiosis and increasing bile acids production are also involved in its anti-NAFLD role. This review summarises the different molecular mechanisms underlying the protective role of capsaicin against NAFLD and ALD. More experimental studies are needed to clarify the effects of capsaicin on the expression of genes involved in hepatic lipid metabolism and hepatocytes apoptosis in NAFLD and ALD.

Introduction: Insulin secretion is a highly regulated process critical for maintaining glucose homeostasis. This abstract explores the intricate interplay between three essential pathways: The Triggering Pathway, The Metabolic Amplifying Pathway, and Cellular Transduction, in orchestrating glucose-dependent biphasic insulin secretion.Mechanism: During the triggering pathway, glucose metabolism in pancreatic beta-cells leads to ATP production, closing ATP-sensitive potassium channels and initiating insulin exocytosis. The metabolic amplifying pathway enhances insulin secretion via key metabolites like NADH and glutamate, enhancing calcium influx and insulin granule exocytosis. Additionally, the cellular transduction pathway involves G-protein coupled receptors and cyclic AMP, modulating insulin secretion.Result and Conclusion: These interconnected pathways ensure a dynamic insulin response to fluctuating glucose levels, with the initial rapid phase and the subsequent sustained phase. Understanding these pathways' complexities provides crucial insights into insulin dysregulation in diabetes and highlights potential therapeutic targets to restore glucose-dependent insulin secretion.

Objective: To investigate the effects of tomatidine (Td) on the progression of type 2 diabetes mellitus (T2DM) in mice and uncover the mechanism.

Methods: T2DM mice model was induced by high-fat diet (HFD) and intrabitoneal injection of streptozotocin (STZ). The mice were grouped as follows: 1, control; 2, T2D; 3, T2D + tomatidine (5 mg/kg); 4, T2D + tomatidine (10 mg/kg); 5, T2D + tomatidine (20 mg/kg). Fasting blood glucose was detected by glucose metre and fasting insulin was detected by the kit to determine the effect of Td on T2DM mice. ELISA, qPCR, and Immunoblot assays were performed to detect the effects of Td on the hepatic glucose homeostasis and inflammation of mice. Immunoblot assays further confirmed the mechanism.

Results: Td improved blood glucose and insulin resistance in T2DM mice. In addition, Td improved liver function and lipid metabolism disorder in T2DM mice. Td also affected the liver glucose homeostasis related genes in T2DM mice. Td alleviated serum inflammation in T2DM mice. We further found that Td activated AMPK pathway, therefore ameliorating T2DM.

Conclusion: Td ameliorated HFD/STZ-induced T2DM in mice, suggesting that it could serve as a drug of T2DM.