Archives of Physiology and Biochemistry最新文献

The neem plant (Azadirachta indica) has popular ethnomedicinal applications. The anti-diabetic potential and mechanism of neem seed oil (NSO) in a rodent model of type 2 diabetes mellitus was evaluated in the present study. Experimentally-induced diabetic animals were administered NSO (200 and 400 mg/kg) or metformin (150 mg/kg) orally for 30 days, with some animals serving as positive and negative controls. NSO significantly (p < .05) reversed diabetes-induced impaired glucose metabolism, dyslipidaemia, and oxido-inflammatory imbalances typified by changes in the NADH/NAD+ ratio (p < .001) and increases in the mRNA or protein levels of C-reactive protein, 4-hydroxynonenal, and pro-inflammatory cytokines (TNF-α and Il-1β) among others in the hepatic or pancreatic tissues of diabetic animals. The histological evaluation of the pancreatic tissue corroborated the protective effect of NSO. The findings showed that the antidiabetic effect of NSO proceeded through its hypolipidemic effect and modulation of redox and inflammatory signalling events in the tissues of animals.

Content: The impact of triglyceride levels is important to understand the changes in metabolism and structure. With an increase in obesity and hyperlipidemia due to diet; cardiovascular and neuronal structural changes have been shown to be more distinct.

Objective: This review aims to discuss the pathophysiology and mechanisms involved in increased levels of triglycerides leading to vascular impairment, metabolic syndrome and cognitive decline.

Methods: The literature search was performed using the PubMed, Google scholar and Scopus databases, among which 180 articles were shortlisted based on key words, abstract, materials and methods and results. Among these 74 articles have been cited for the review.

Results and discussion: The review discusses the impact of hypertriglyceridemia on metabolism, triglyceride storage, and neurovascular integrity, highlighting mechanisms contributing to vascular dysfunction, metabolic syndrome, and cognitive deterioration.

Conclusion: Elevated triglyceride levels are a key factor in altering metabolic pathways and structural integrity in cardiovascular and neuronal systems. This review provides insights into the mechanisms underlying metabolic disorders caused by elevated triglyceride levels, It highlights the need for further studies to provide more supportive evidence and address existing limitations in understanding these changes.

The introduction of Tyrosine Kinase Inhibitors (TKIs) has revolutionised cancer treatment, yet concerns regarding cardiovascular toxicity have surfaced. This piece delves into the interplay between AMP-activated protein kinase (AMPK) signalling and TKI-induced cardiovascular toxicity. The study unravels the intricate relationship between AMPK activation and TKI-induced cardiovascular toxicity, aiming to ascertain whether AMPK can play a strategic role in mitigating adverse effects. Beyond unravelling mechanistic insights, the research sets the stage for future therapeutic approaches, envisioning AMPK activation as a pivotal connection for balancing effective cancer treatment with cardiovascular well-being. As research advances, the potential of AMPK activation not only addresses challenges in TKI-induced cardiovascular toxicity but also shapes the future landscape of personalised anticancer therapies. The article explores the mechanisms of TKI-induced toxicity, AMPK's impact on cardiovascular health, and the potential therapeutic implications of AMPK activation in alleviating TKI-associated toxicities.

One of the undesirable complications of diabetes is sexual dysfunctions in males which may affect their fertility. This research aims to study the effect of C-peptide administration on the prostate of diabetic rats and focusing on exploring the role of the autophagy pathway in diabetic prostate and whether it is involved in C-peptide action. Forty adult male Wistar albino rats were separated into control group, diabetic group, diabetic + C-peptide and diabetic + C-peptide + 3-Methyladenine (autophagy inhibitor). Serum metabolic parameters and prostatic specific antigen (PSA) were measured. Markers of oxidative stress, inflammation, fibrosis, cell proliferation and cell autophagy were evaluated in prostate tissues using biochemical, western blotting and immunohistochemical techniques. C-peptide administration ameliorated the effects of diabetes on the prostate through its hypoglycaemic, antioxidant, anti-inflammatory, and antiproliferative effects which were reversed with autophagy inhibition. Thus, we concluded that C-peptide prevented the effects of diabetes on the prostate through stimulation of the autophagy pathway.

Context: Insulin resistance and a disturbed lipid profile are common associations with type 2 diabetes mellitus (T2DM) and different skin diseases, particularly psoriasis (PsO).

Objectives: We investigated potential therapeutic mechanisms of metformin in a murine animal model of psoriasiform lesions in T2DM.

Materials and methods: Forty-two rats were randomly divided into control, PsO, and type II DM (T2DM) groups. After confirmation of DM, the type II diabetic rats were allocated into T2DM+ PsO, T2DM+ PsO+ systemic metformin (S. met), T2DM+ PsO+ topical metformin (T. met)), and T2DM+ PsO + combined metformin (C. met). PsO was induced by topical imiquimod.

Results: Systemic administration of the cornerstone antidiabetic drug, metformin, was able to improve insulin resistance and lipid profile. At molecular levels, both topical and systemic metformin significantly increased AMP-activated protein kinase (AMPK), and lowered keratinocyte growth factor (KGF) / "Signal transducer and activator of transcription" (STAT)3 protein levels, and the IL-17RA and IL-17RC gene expression.

Conclusion: Although its glucose-controlling effect was not optimum, T.met gel served anti-psoriatic and anti-inflammatory effects.

Helicobacter pylori infection has been associated with the development of insulin resistance (IR). This study aimed to examine the effect of H. pylori-derived extracellular vesicles (EVs) on IR induction. EVs were derived from two H. pylori strains, and characterised by transmission electron microscopy and dynamic light scattering. Different concentrations of insulin were added to HepG2 cells to induce IR model. HepG2 cells were exposed to various concentrations of H. pylori-derived EVs to assess IR development. The gene expression of IRS1, AKT2, GLUT2, IL-6, SOCS3, c-Jun and miR-140 was examined using RT-qPCR. Glucose uptake analysis revealed insulin at 5 × 10 ^-7mol/l and EVs at 50 µg/ml induced IR model in HepG2 cells. H. pylori-derived EVs downregulated the expression level of IRS1, AKT2, and GLUT2, and upregulated IL-6, SOCS3, c-Jun, and miR-140 expression in HepG2 cells. In conclusion, our findings propose a novel mechanism by which H. pylori-derived EVs could potentially induce IR.

Context: Energy homeostasis is a primary factor for the survival of mammals. Many tissues and organs, among which is the liver, keep this homeostasis in varied circumstances, including caloric restriction (CR) and physical activity.

Objective: This study investigated glucose metabolism using the following groups of eight-week-old male Swiss mice: CS, sedentary and fed freely; RS, sedentary and RT, trained, both under 30% CR (n = 20-23 per group).

Results: Organs and fat depots of groups RS and RT were similar to CS, although body weight was lower. CR did not impair training performance nor affected systemic or hepatic glucose metabolism. Training combined with CR (group RT) improved in vivo glucose tolerance and did not affect liver gluconeogenesis.

Conclusions: The mice tolerated the prolonged moderate CR without impairment of their well-being, glucose homeostasis, and resistance training performance. But the higher liver gluconeogenic efficiency previously demonstrated using this training protocol in mice was not evidenced under CR.

Background: Diabetes patients' quality of life can be severely impacted by diabetic muscle atrophy.Aim: This study aimed to explore the impact of high-intensity exercise (HIE) alongside insulin treatment on muscle atrophy in a rat model of type 1 diabetes mellitus (T1DM).Methodology: Fifty rats were allocated into five groups; Group 1, control sedentary (CS), T1DM was elicited in the rest of the groups by giving them Streptozotocin (STZ) (60 mg/kg), where group 2 (DS) remained sedentary, while groups 3,4,5 were treated with insulin after induction of diabetes. Group 4 (DI+MIE) and 5 (DI+ HIE) underwent moderate and high-intensity exercise, respectively.Results: HIE for 14 days combined with insulin treatment significantly restored muscle strength and mass with a significant modification in the mitophagy-related proteins and fibroblast growth factor 21 (FGF 21) compared to other treated groups.Conclusion: This study concluded that there is a therapeutic role for HIE with insulin against T1DM-induced muscle atrophy.

Background: Obese adipose tissue produces various pro-inflammatory cytokines that are major contributors to adipose tissue inflammation.

Objective: The present study aimed to determine the effects of HM-chromanone (HMC) against obesity and adipose tissue inflammation in high-fat diet-fed mice.

Materials and methods: Twenty-four C57BL/6J male mice were divided into three groups: ND (normal diet), HFD (high-fat diet), and HFD + HMC. The ND group was fed a normal diet, whereas the HFD and HFD + HMC groups were fed a high-fat diet. After 10 weeks of feeding, the animals were orally administered the treatments daily for 9 weeks. The ND and HFD group received distilled water as treatment. The HFD+HMC group was treated with HM-chromaone (50 mg/kg).

Results: HM-chromanone administration decreased body weight, fat mass, and adipocyte diameter. HM-chromanone also improved plasma lipid profiles, decreased leptin levels, and increased adiponectin levels. The inhibiting effect of HM-chromanone on SREBP-1c, PPARγ, C/EBPα, and FAS decreased adipogenesis, thereby alleviating lipid accumulation. Furthermore, HM-chromanone administration exhibited a reduction in macrophage infiltration and the expression of pro-inflammatory cytokines. HM-chromanone suppressed the phosphorylation of IκBα and NF-κB, leading to the inhibition of iNOS and COX2 expressions, resulting in decreased inflammation in adipose tissue.

Discussion and conclusion: These results highlight the anti-obesity and anti-inflammatory properties of HM-chromanone, achieved through the downregulation of the SREBP-1c and NF-κB pathway in high-fat diet-fed mice.