Effect of Intermittent Fasting on Improve Body Composition and Anthropometric Measurements of Women with Polycystic Ovarian Syndrome / Efecto del ayuno intermitente para mejorar la composición corporal y las medidas antropométricas de mujeres con síndrome de ovario poliquístico

Introduction: Polycystic ovary syndrome is a metabolicdisorder that affects women of reproductive age and is associated with insulin resistance.Objectives: The study aims to evaluate the effect of intermittent fasting and dietary intervention in improving anthropometric measures and body composition.Material and Methods: An interventional trial was carriedout on eighty-six women between the ages of 19 and 40 with a body mass index of more than 25 kg/m2 were assigned to two intervention groups: the first group (n = 57) followed intermittent fasting plus dietary restriction, and the second group (n = 29) followed dietary restriction without intermittent fasting.Results: The results show that the fasting polycystic ovarian syndrome women experienced a significant (P < 0.05) increase in muscle mass (2.2 ± 2.4) compared to the non-fasting group (0.01 ± 1.5). At the end of the intervention, fasting women with the polycystic ovarian syndrome had significantly (P < 0.05) lost weight (9.2 ± 4.5kg), fat mass % (4.6 ± 3.4), and visceral fat (2.3 ± 2.1 kg), while gaining muscle mass (2.2 ± 2.4 kg). However, non-fasting women with polycystic ovarian syndrome showed significantly reduced body weight (2.4 ± 0.4 kg), fat mass % (1.2 ± 1.1), and visceral fat (0.5 ± 0.7). The results of the linear regression model showed that the highest effect of intermittent fasting was seen in weight, fat-free mass, and muscle mass. Body fat mass changed by 93% under the effect of intermittent fasting.Conclusion: Intermittent fasting may improve health outcomes, reduce body fat, maintain muscle mass, and aidweight loss in women with polycystic ovarian syndrome.Large-scale randomized controlled trials can improve our understanding of intermittent fasting in polycystic ovarian syndrome.(AU)

Ferroptosis inhibitors reduce celastrol toxicity and preserve its insulin sensitizing effects in insulin resistant HepG2 cells.

OBJECTIVE: Research has shown that celastrol can effectively treat a variety of diseases, yet when passing a certain dosage threshold, celastrol becomes toxic, causing complications such as liver and kidney damage and erythrocytopenia, among others. With this dichotomy in mind, it is extremely important to find ways to preserve celastrol's efficacy while reducing or preventing its toxicity. METHODS: In this study, insulin-resistant HepG2 (IR-HepG2) cells were prepared using palmitic acid and used for in vitro experiments. IR-HepG2 cells were treated with celastrol alone or in combination with N-acetylcysteine (NAC) or ferrostatin-1 (Fer-1) for 12, 24 or 48 h, at a range of doses. Cell counting kit-8 assay, Western blotting, quantitative reverse transcription-polymerase chain reaction, glucose consumption assessment, and flow cytometry were performed to measure celastrol's cytotoxicity and whether the cell death was linked to ferroptosis. RESULTS: Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-HepG2 cells. Celastrol downregulated glutathione peroxidase 4 (GPX4) mRNA. Molecular docking models predicted that solute carrier family 7 member 11 (SLC7A11) and GPX4 were covalently bound by celastrol. Importantly, we found for the first time that the application of ferroptosis inhibitors (especially NAC) was able to reduce celastrol's toxicity while preserving its ability to improve insulin sensitivity in IR-HepG2 cells. CONCLUSION: One potential mechanism of celastrol's cytotoxicity is the induction of ferroptosis, which can be alleviated by treatment with ferroptosis inhibitors. These findings provide a new strategy to block celastrol's toxicity while preserving its therapeutic effects. Please cite this article as: Liu JJ, Zhang X, Qi MM, Chi YB, Cai BL, Peng B, Zhang DH. Ferroptosis inhibitors reduce celastrol toxicity and preserve its insulin sensitizing effects in insulin resistant HepG2 cells. J Integr Med. 2024; 22(3): 286-294.

Rikkunshito increases peripheral incretin-hormone levels in humans and rats.

BACKGROUND: It was reported that rikkunshito (TJ-43) improved the cisplatin-induced decreases in the active form of ghrelin in plasma; however, other effects on gastrointestinal hormones have not been investigated. AIM: To investigate the effects of TJ-43 on peripheral levels of incretin hormones, including gastric inhibitory polypeptide (GIP) and glucagon-like polypeptide-1 (GLP-1), in humans and rats. METHODS: Patients were divided into two groups, namely patients who received TJ-43 immediately following surgery [TJ-43(+) group] and those who received TJ-43 on postoperative day 21 [TJ-43(-) group], and the plasma levels of active GIP and active GLP-1 were assessed. In animal experiments, rats were treated with TJ-43 [rat (r)TJ-43(+) group] or without [rTJ-43(-) group] by gavage for 4 wk, and the plasma active GIP and active GLP-1 levels were measured. The expression of incretin hormones in the gastrointestinal tract and insulin in the pancreas were investigated by immunohistochemistry. Furthermore, the cyclic adenosine monophosphate activities were assessed in pancreatic tissues from rats treated with or without TJ-43 in vivo, and the blood glucose levels and plasma insulin levels were measured in rats treated with or without TJ-43 in oral glucose tolerance tests. RESULTS: In humans, the active incretin hormone levels increased, and values were significantly greater in the TJ-43(+) group compared those in the TJ-43(-) group. In rats, the plasma active incretin levels significantly increased in the rTJ-43(+) group compared with those in the rTJ-43(-) group. GIP and GLP-1 expressions were enhanced by TJ-43 treatment. Moreover, plasma insulin levels increased and blood glucose levels were blunted in the rTJ-43(+) group. CONCLUSION: The results show that TJ-43 may be beneficial for patients who undergo pancreatic surgery.

Chinese herbal medicine decreases incidence of hepatocellular carcinoma in diabetes mellitus patients with regular insulin management.

BACKGROUND: Type 2 diabetes mellitus (DM) is an independent risk factor for hepatocellular carcinoma (HCC), while insulin is a potent mitogen. Identifying a new therapeutic modality for preventing insulin users from developing HCC is a critical goal for researchers. AIM: To investigate whether regular herbal medicine use can decrease HCC risk in DM patients with regular insulin control. METHODS: We used data acquired from the Taiwanese National Health Insurance research database between 2000 and 2017. We identified patients with DM who were prescribed insulin for > 3 months. The herb user group was further defined as patients prescribed herbal medication for DM for > 3 months per annum during follow-up. We matched the herb users to nonusers at a 1:3 ratio according to age, sex, comorbidities and index year by propensity score matching. We analyzed HCC incidence, HCC survival rates, and the herbal prescriptions involved. RESULTS: We initially enrolled 657144 DM patients with regular insulin use from 2000 to 2017. Among these, 46849 patients had used a herbal treatment for DM, and 140547 patients were included as the matched control group. The baseline variables were similar between the herb users and nonusers. DM patients with regular herb use had a 12% decreased risk of HCC compared with the control group [adjusted hazard ratio (aHR) = 0.88, 95%CI = 0.80-0.97]. The cumulative incidence of HCC in the herb users was significantly lower than that of the nonusers. Patients with a herb use of > 5 years cumulatively exhibited a protective effect against development of HCC (aHR = 0.82, P < 0.05). Of patients who developed HCC, herb users exhibited a longer survival time than nonusers (aHR = 0.78, P = 0.0001). Additionally, we report the top 10 herbs and formulas in prescriptions and summarize the potential pharmacological effects of the constituents. Our analysis indicated that Astragalus propinquus (Huang Qi) plus Salvia miltiorrhiza Bunge (Dan Shen), and Astragalus propinquus (Huang Qi) plus Trichosanthes kirilowii Maxim. (Tian Hua Fen) were the most frequent combination of single herbs. Meanwhile, Ji Sheng Shen Qi Wan plus Dan Shen was the most frequent combination of herbs and formulas. CONCLUSION: This large-scale retrospective cohort study reveals that herbal medicine may decrease HCC risk by 12% in DM patients with regular insulin use.

Effects of vitamin family members on insulin resistance and diabetes complications.

The following letter to the editor highlights the article "Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance" in World J Diabetes 2023 Oct 15; 14 (10): 1514-1523. It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.

Excessive Tryptophan and Phenylalanine Induced Pancreatic Injury and Glycometabolism Disorder in Grower-finisher Pigs.

BACKGROUND: The increase in circulating insulin levels is associated with the onset of type 2 diabetes (T2D), and the levels of branched-chain amino acids and aromatic amino acids (AAAs) are altered in T2D, but whether AAAs play a role in insulin secretion and signaling remains unclear. OBJECTIVES: This study aimed to investigate the effects of different AAAs on pancreatic function and on the use of insulin in finishing pigs. METHODS: A total of 18 healthy finishing pigs (Large White) with average body weight of 100 ± 1.15 kg were randomly allocated to 3 dietary treatments: Con, a normal diet supplemented with 0.68% alanine; Phe, a normal diet supplemented with 1.26% phenylalanine; and Trp, a normal diet supplemented with 0.78% tryptophan. The 3 diets were isonitrogenous. There were 6 replicates in each group. RESULTS: Herein, we investigated the effects of tryptophan and phenylalanine on pancreatic function and the use of insulin in finishing pigs and found that the addition of tryptophan and phenylalanine aggravated pancreatic fat deposition, increased the relative content of saturated fatty acids, especially palmitate (C16:0) and stearate (C18:0), and the resulting lipid toxicity disrupted pancreatic secretory function. We also found that tryptophan and phenylalanine inhibited the growth and secretion of ß-cells, downregulated the gene expression of the PI3K/Akt pathway in the pancreas and liver, and reduced glucose utilization in the liver. CONCLUSIONS: Using fattening pigs as a model, multiorgan combined analysis of the insulin-secreting organ pancreas and the main insulin-acting organ liver, excessive intake of tryptophan and phenylalanine will aggravate pancreatic damage leading to glucose metabolism disorders, providing new evidence for the occurrence and development of T2D.

Ketone Monoester Followed by Carbohydrate Ingestion after Glycogen-Lowering Exercise Does Not Improve Subsequent Endurance Cycle Time Trial Performance.

Relative to carbohydrate (CHO) alone, exogenous ketones followed by CHO supplementation during recovery from glycogen-lowering exercise have been shown to increase muscle glycogen resynthesis. However, whether this strategy improves subsequent exercise performance is unknown. The objective of this study was to assess the efficacy of ketone monoester (KME) followed by CHO ingestion after glycogen-lowering exercise on subsequent 20 km (TT20km) and 5 km (TT5km) best-effort time trials. Nine recreationally active men (175.6 ± 5.3 cm, 72.9 ± 7.7 kg, 28 ± 5 y, 12.2 ± 3.2% body fat, VO2max = 56.2 ± 5.8 mL· kg BM-1·min-1; mean ± SD) completed a glycogen-lowering exercise session, followed by 4 h of recovery and subsequent TT20km and TT5km. During the first 2 h of recovery, participants ingested either KME (25 g) followed by CHO at a rate of 1.2 g·kg-1·h-1 (KME + CHO) or an iso-energetic placebo (dextrose) followed by CHO (PLAC + CHO). Blood metabolites during recovery and performance during the subsequent two-time trials were measured. In comparison to PLAC + CHO, KME + CHO displayed greater (p < 0.05) blood beta-hydroxybutyrate concentration during the first 2 h, lower (p < 0.05) blood glucose concentrations at 30 and 60 min, as well as greater (p < 0.05) blood insulin concentration 2 h following ingestion. However, no treatment differences (p > 0.05) in power output nor time to complete either time trial were observed vs. PLAC + CHO. These data indicate that the metabolic changes induced by KME + CHO ingestion following glycogen-lowering exercise are insufficient to enhance subsequent endurance time trial performance.

Brain-Derived Neurotrophic Factor as a Potential Mediator of the Beneficial Effects of Myo-Inositol Supplementation during Suckling in the Offspring of Gestational-Calorie-Restricted Rats.

This study aims to investigate the potential mechanisms underlying the protective effects of myo-inositol (MI) supplementation during suckling against the detrimental effects of fetal energy restriction described in animal studies, particularly focusing on the potential connections with BDNF signaling. Oral physiological doses of MI or the vehicle were given daily to the offspring of control (CON) and 25%-calorie-restricted (CR) pregnant rats during suckling. The animals were weaned and then fed a standard diet until 5 months of age, when the diet was switched to a Western diet until 7 months of age. At 25 days and 7 months of age, the plasma BDNF levels and mRNA expression were analyzed in the hypothalamus and three adipose tissue depots. MI supplementation, especially in the context of gestational calorie restriction, promoted BDNF secretion and signaling at a juvenile age and in adulthood, which was more evident in the male offspring of the CR dams than in females. Moreover, the CR animals supplemented with MI exhibited a stimulated anorexigenic signaling pathway in the hypothalamus, along with improved peripheral glucose management and enhanced browning capacity. These findings suggest a novel connection between MI supplementation during suckling, BDNF signaling, and metabolic programming, providing insights into the mechanisms underlying the beneficial effects of MI during lactation.

Thermotherapy has Sexually Dimorphic Responses in APP/PS1 Mice.

A thermoregulatory decline occurs with age due to changes in muscle mass, vasoconstriction, and metabolism that lowers core body temperature (Tc). Although lower Tc is a biomarker of successful aging, we have previously shown this worsens cognitive performance in the APP/PS1 mouse model of Alzheimer's disease (AD) [1]. We hypothesized that elevating Tc with thermotherapy would improve metabolism and cognition in APP/PS1 mice. From 6-12 months of age, male and female APP/PS1 and C57BL/6 mice were chronically housed at 23 or 30°C. At 12 months of age, mice were assayed for insulin sensitivity, glucose tolerance, and spatial cognition. Plasma, hippocampal, and peripheral (adipose, hepatic, and skeletal muscle) samples were procured postmortem and tissue-specific markers of amyloid accumulation, metabolism, and inflammation were assayed. Chronic 30°C exposure increased Tc in all groups except female APP/PS1 mice. All mice receiving thermotherapy had either improved glucose tolerance or insulin sensitivity, but the underlying processes responsible for these effects varied across sexes. In males, glucose regulation was influenced predominantly by hormonal signaling in plasma and skeletal muscle glucose transporter 4 expression, whereas in females, this was modulated at the tissue level. Thermotherapy improved spatial navigation in male C57BL/6 and APP/PS1 mice, with the later attributed to reduced hippocampal soluble amyloid-ß (Aß)42. Female APP/PS1 mice exhibited worse spatial memory recall after chronic thermotherapy. Together, the data highlights the metabolic benefits of passive thermotherapy with potential nonpharmacological management for some individuals with AD, and provides further evidence for the necessity of adopting personalized patient care.

Alpha lipoic acid administration improved both peripheral sensitivity to insulin and liver clearance of insulin reducing potential risk of diabetes and nonalcoholic fatty liver disease in overweight/obese PCOS patients.

OBJECTIVE: To evaluate the effects of alpha lipoic acid (ALA) on hormonal and metabolic parameters in a group of overweight/obese Polycystic Ovary Syndrome (PCOS) patients. METHODS: This was a retrospective study in which thirty-two overweight/obese patients with PCOS (n = 32) not requiring hormonal treatment were selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of complementary treatment with ALA (400 mg/day). Hepatic Insulin Extraction (HIE) index was also calculated. RESULTS: ALA administration significantly improved insulin sensitivity and decreased ALT and AST plasma levels in all subjects, though no changes were observed on reproductive hormones. When PCOS patients were subdivided according to the presence or absence of familial diabetes background, the higher effects of ALA were observed in the former group that showed AST and ALT reduction and greater HIE index decrease. CONCLUSION: ALA administration improved insulin sensitivity in overweight/obese PCOS patients, especially in those with familial predisposition to diabetes. ALA administration improved both peripheral sensitivity to insulin and liver clearance of insulin. Such effects potentially decrease the risk of nonalcoholic fat liver disease and diabetes in PCOS patients.

Selenium, diabetes, and their intricate sex-specific relationship.

Selenium (Se) is an essential trace element, which is inserted as selenocysteine (Sec) into selenoproteins during biosynthesis, orchestrating their expression and activity. Se is associated with both beneficial and detrimental health effects; deficient supply or uncontrolled supplementation raises concerns. In particular, Se was associated with an increased incidence of type 2 diabetes (T2D) in a secondary analysis of a randomized controlled trial (RCT). In this review, we discuss the intricate relationship between Se and diabetes and the limitations of the available clinical and experimental studies. Recent evidence points to sexual dimorphism and an association of Se deficiency with gestational diabetes mellitus (GDM). We highlight the emerging evidence linking high Se status with improved prognosis in patients with T2D and lower risk of macrovascular complications.

The Lipophilic Extract from Ginkgo biloba L. Leaves Promotes Glucose Uptake and Alleviates Palmitate-Induced Insulin Resistance in C2C12 Myotubes.

Ginkgo biloba L. (ginkgo) is a widely used medicinal plant around the world. Its leaves, which have been used as a traditional Chinese medicine, are rich in various bioactive components. However, most of the research and applications of ginkgo leaves have focused on terpene trilactones and flavonol glycosides, thereby overlooking the other active components. In this study, a lipophilic extract (GL) was isolated from ginkgo leaves. This extract is abundant in lipids and lipid-like molecules. Then, its effect and potential mechanism on glucose uptake and insulin resistance in C2C12 myotubes were investigated. The results showed that GL significantly enhanced the translocation of GLUT4 to the plasma membrane, which subsequently promoted glucose uptake. Meanwhile, it increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream targets. Both knockdown of AMPK with siRNA and inhibition with AMPK inhibitor compound C reversed these effects. Additionally, GL ameliorated palmitate-induced insulin resistance by enhancing insulin-stimulated glucose uptake, increasing the phosphorylation of protein kinase B (PKB/AKT), and restoring the translocation of GLUT4 from the cytoplasm to the membrane. However, pretreatment with compound C abolished these beneficial effects of GL. In conclusion, GL enhances basal glucose uptake in C2C12 myotubes and improves insulin sensitivity in palmitate-induced insulin resistant myotubes through the AMPK pathway.

Vitamin D and Insulin-Dependent Diabetes: A Systematic Review of Clinical Trials.

(1) Background: Vitamin D supplementation after type 1 diabetes mellitus (T1DM) onset has led to conflicting results on beta-cell preservation. Aim: This paper presents a systematic review to verify whether randomized prospective controlled trials (RCTs) demonstrate that improved vitamin D status confers protection on T1DM. (2) Methods: A systematic review was conducted up until 18 January 2024 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching MEDLINE, MEDLINE In-Process, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials, using keywords "vitamin D", "type 1 diabetes", and "children". (3) Results: Following the above-mentioned search process, 408 articles in PubMed and 791 in Embase met inclusion criteria. After removing duplicates, 471 articles remained. After exclusion criteria, 11 RCTs remained. Because of major heterogeneity in design and outcomes, no meta-analyses were conducted, allowing only for qualitative analyses. There was no strong evidence that vitamin D supplementation has lasting effects on beta-cell preservation or glycemic control in new-onset T1DM. (4) Conclusions: More rigorous, larger studies are needed to demonstrate whether vitamin D improves beta-cell preservation or glycemic control in new-onset T1DM. Because T1DM may cause osteopenia, it is advisable that patients with new onset T1DM have adequate vitamin D stores.

The Discovery of New Inhibitors of Insulin-Regulated Aminopeptidase by a High-Throughput Screening of 400,000 Drug-like Compounds.

With the ambition to identify novel chemical starting points that can be further optimized into small drug-like inhibitors of insulin-regulated aminopeptidase (IRAP) and serve as potential future cognitive enhancers in the clinic, we conducted an ultra-high-throughput screening campaign of a chemically diverse compound library of approximately 400,000 drug-like small molecules. Three biochemical and one biophysical assays were developed to enable large-scale screening and hit triaging. The screening funnel, designed to be compatible with high-density microplates, was established with two enzyme inhibition assays employing either fluorescent or absorbance readouts. As IRAP is a zinc-dependent enzyme, the remaining active compounds were further evaluated in the primary assay, albeit with the addition of zinc ions. Rescreening with zinc confirmed the inhibitory activity for most compounds, emphasizing a zinc-independent mechanism of action. Additionally, target engagement was confirmed using a complementary biophysical thermal shift assay where compounds causing positive/negative thermal shifts were considered genuine binders. Triaging based on biochemical activity, target engagement, and drug-likeness resulted in the selection of 50 qualified hits, of which the IC50 of 32 compounds was below 3.5 µM. Despite hydroxamic acid dominance, diverse chemotypes with biochemical activity and target engagement were discovered, including non-hydroxamic acid compounds. The most potent compound (QHL1) was resynthesized with a confirmed inhibitory IC50 of 320 nM. Amongst these compounds, 20 new compound structure classes were identified, providing many new starting points for the development of unique IRAP inhibitors. Detailed characterization and optimization of lead compounds, considering both hydroxamic acids and other diverse structures, are in progress for further exploration.

Pharmacological and phytochemical insights on the pancreatic ß-cell modulation by Angelica L. roots.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica roots are a significant source of traditional medicines for various cultures around the northern hemisphere, from indigenous communities in North America to Japan. Among its many applications, the roots are used to treat type 2 diabetes mellitus; however, this application is not mentioned often. Ethnopharmacological studies have reported the use of A. japonica var. hirsutiflora, A. furcijuga, A. shikokiana, and A. keiskei to treat diabetes symptoms, and further reports have demonstrated the three angelica roots, i.e., A. japonica var. hirsutiflora, A. reflexa, and A. dahurica, exhibit insulin secretagogue activity. AIM OF THE STUDY: This study aimed to phytochemically characterize and compare angelica roots monographed in the European Pharmacopeia 11th, isolate major plant metabolites, and assess extracts and isolates' capability to modulate pancreatic ß-cell function. MATERIALS AND METHODS: Root extracts of Angelica archangelica, Angelica dahurica, Angelica biserrata, and Angelica sinensis were phytochemically profiled using liquid chromatography method coupled with mass spectrometry. Based on this analysis, simple and furanocoumarins were isolated using chromatography techniques. Extracts (1.6-50 µg/mL) and isolated compounds (5-40 µmol/L) were studied for their ability to modulate insulin secretion in the rat insulinoma INS-1 pancreatic ß-cell model. Insulin was quantified by the homogeneous time-resolved fluorescence method. RESULTS: Forty-one secondary metabolites, mostly coumarins, were identified in angelica root extracts. A. archangelica, A. dahurica, and A. biserrata root extracts at concentration of 12.5-50 µg/mL potentiated glucose-induced insulin secretion, which correlated with their high coumarin content. Subsequently, 23 coumarins were isolated from these roots and screened using the same protocol. Coumarins substituted with the isoprenyl group were found to be responsible for the extracts' insulinotropic effect. CONCLUSIONS: Insulinotropic effects of three pharmacopeial angelica roots were found, the metabolite profiles and pharmacological activities of the roots were correlated, and key structures responsible for the modulation of pancreatic ß-cell function were identified. These findings may have implications for the traditional use of angelica roots in treating diabetes. Active plant metabolites may also become lead structures in the search for new antidiabetic treatments.

Is chromium(III) pharmacologically relevant? An update focused on studies with diabetic rodent models.

A decade ago, the author assessed the status of chromium as the trivalent ion as an essential element and as a therapeutic agent based on rodent studies for this journal. The current review was undertaken to update considerations regarding the status of chromium, focusing on studies of Cr supplementation of diabetic rodent models over the last decade. Cr can no longer be considered an essential trace element for humans. Observed effects of Cr on rodent models of insulin resistance and diabetes are best interpreted in terms of a pharmacological role for Cr. The review of studies on the effects of Cr on rat models of diabetes is updated, and the results continue to suggest Cr increases insulin sensitivity in peripheral tissues of the rodent models. The lack of effects in human studies may stem from humans receiving a comparably smaller dose than the rodent models. However, given the different responses to Cr in the rodent models, humans could potentially have different responses to Cr. Recent studies primary utilizing rodents suggest two potential complementary but also contradictory modes of action for Cr(III) at a molecular level.

Seaweeds as Nutraceutical Elements and Drugs for Diabetes Mellitus: Future Perspectives.

Diabetes mellitus is a chronic metabolic condition marked by high blood glucose levels caused by inadequate insulin synthesis or poor insulin use. This condition affects millions of individuals worldwide and is linked to a variety of consequences, including cardiovascular disease, neuropathy, nephropathy, and retinopathy. Diabetes therapy now focuses on controlling blood glucose levels through lifestyle changes, oral medicines, and insulin injections. However, these therapies have limits and may not successfully prevent or treat diabetic problems. Several marine-derived chemicals have previously demonstrated promising findings as possible antidiabetic medicines in preclinical investigations. Peptides, polyphenols, and polysaccharides extracted from seaweeds, sponges, and other marine species are among them. As a result, marine natural products have the potential to be a rich source of innovative multitargeted medications for diabetes prevention and treatment, as well as associated complications. Future research should focus on the chemical variety of marine creatures as well as the mechanisms of action of marine-derived chemicals in order to find new antidiabetic medicines and maximize their therapeutic potential. Based on preclinical investigations, this review focuses on the next step for seaweed applications as potential multitargeted medicines for diabetes, highlighting the bioactivities of seaweeds in the prevention and treatment of this illness.

Centella asiatica mitigates the detrimental effects of Bisphenol-A (BPA) on pancreatic islets.

Bisphenol-A (BPA) is widely used in food packaging and household products, leading to daily human exposure and potential health risks including metabolic diseases like type 2 diabetes mellitus (T2DM). Understanding BPA's mechanisms and developing intervention strategies is urgent. Centella asiatica, a traditional herbal medicine containing pentacyclic triterpenoids, shows promise due to its antioxidant and anti-inflammatory properties, utilized for centuries in Ayurvedic therapy. We investigated the effect of Centella asiatica (CA) ethanol extract on BPA-induced pancreatic islet toxicity in male Swiss albino mice. BPA administration (10 and 100 µg/kg body weight, twice daily) for 21 days caused glucose homeostasis disturbances, insulin resistance, and islet dysfunction, which were partially mitigated by CA supplementation (200 and 400 mg/kg body weight). Additionally, heightened oxidative stress, elevated levels of proinflammatory cytokines, loss of mitochondrial membrane potential (MMP), abnormal cell cycle, and increased apoptosis were implicated in the detrimental impact of BPA on the endocrine pancreas which were effectively counteracted by CA supplementation. In summary, CA demonstrated a significant ability to mitigate BPA-induced apoptosis, modulate redox homeostasis, alleviate inflammation, preserve MMP, and regulate the cell cycle. As a result, CA emerged as a potent agent in neutralizing the diabetogenic effects of BPA to a considerable extent.

Lycium Barbarum Polysaccharides Improves Cognitive Functions in ICV-STZ-Induced Alzheimer's Disease Mice Model by Improving the Synaptic Structural Plasticity and Regulating IRS1/PI3K/AKT Signaling Pathway.

Lycium barbarum polysaccharide (LBP) have a certain curative effect on hypoglycemic and neuroprotective effects, but the specific mechanism is unclear and needs to be further explored. This study aimed to clarify the mechanisms of LBP in the treatment of ICV-STZ mice model of AD from the perspectives of insulin resistance, IRS1/PI3K/AKT signaling pathway, and synaptic protein expression. We used male C57BL/6J mice injected with STZ (3 mg/kg) in the lateral ventricle as an AD model. After treatment with LBP, the learning and memory abilities of ICV-STZ mice were enhanced, and the pathological changes in brain tissue were alleviated. LBP can regulate the expression of proteins related to the IRS1/PI3K/AKT signaling pathway and thereby reducing Aß deposition and tau protein phosphorylation in the brain of ICV-STZ mice. In addition, LBP also can up-regulate the expression of synaptic proteins. The results indicated that LBP played a neuroprotective role by regulating the IRS1/PI3K/AKT pathway, inhibiting tau protein hyperphosphorylation and improving the expression levels of synapse-related proteins.

The effect of Artemisia annua L. aqueous and methanolic extracts on insulin signaling in liver of HFD/STZ diabetic mice.

OBJECTIVES: Many studies have shown the anti-diabetic effects of medicinal plants. But their molecular mechanism has been less studied. Understanding of these mechanisms can help to better manage the treatment of diabetes by using these plants. So, this research examined the effect of Artemisia annua extract on PI3K (phosphatidylinositol 3-kinase)/AKt (serine/threonine kinase protein B) signaling pathway in liver of high-fat diet (HFD)/Streptozotocin (STZ)-induced type 2 diabetic mice. METHODS: Groups of mice were control, untreated diabetic mice, diabetic mice treated with various doses (400, 200, 100 mg/kg) of methanolic and aqueous extract of A. annua and metformin for four weeks. Type 2 diabetes was produced by feeding high-fat diet following injection of low dose of STZ. After experiment duration all mice were sacrificed and blood glucose, insulin, homeostasis model assessment of insulin resistance index (HOMA-IR), index of insulin sensitivity index (ISI) were detected and liver tissues were isolated for to detect m-RNA expression of PI3K and Akt. RESULTS: Extracts of aqueous and methanolic this plant markedly reduced hyperglycemia, hyperinsulinemia, HOMA-IR and elevated ISI in diabetic group in comparison with un-treated diabetic mice. In addition, they could enhance the expression of AKt and PI3K m-RNA in liver tissues in diabetic mice. CONCLUSIONS: Artemisia annua extract ameliorated insulin resistance and improved insulin action in liver via the high activity of PI3K/AKt signaling pathway. So, it can be a suitable alternative treatment to synthetic antidiabetic drugs to improve insulin action in condition of type 2 diabetes.