Lower Blood Glucose Research Articles

Development of food for special dietary uses of diabetes based on oyster mushroom and brown rice

Diabetes patients often struggle to meet their energy requirements, prompting the suggestion of utilizing Food for Special Dietary Uses (FSDU). Previous research has shown the efficacy of oyster mushrooms’ B-glucan in controlling hyperglycemia and insulin resistance. Brown rice, high in magnesium and fiber with a low glycemic index, is known to lower blood glucose levels. Utilizing both ingredients in FSDU may provide products with recommended energy value, nutrient ingredients, and glycemic index. This study aimed to measure the energy, protein, fat, carbohydrate, fiber, glucose, and glycemic index of four mixed formulations of oyster mushrooms and brown rice, along with a control.The study used a true experimental design with a completely randomized research design. The formulations included: P1=9% mixture of moringa and fish flour, P2=10% mixture of carrot and fish flour, F3=11% mixture of moringa and tempeh flour, and F4=12% tempeh flour. The total energy was measured using various methods: adiabatic oxygen bomb calorimeter for energy, Kjeldahl for protein, Soxhlet for fat, by-difference for carbohydrates, AOAC enzymatic-gravimetric for total dietary fiber, anthrone for total sugar, and blood glucose tests at 0, 15, 30, 45, 60, 90, and 120 minutes post-test-food ingestion for glycemic index measurements. Statistical analysis was performed using the One-Way ANOVA and Kruskal-Wallis tests.The research results indicate significant differences in energy, protein, fat, carbohydrates, total sugar, and fiber values among groups (p<0.01). The lowest glycemic index was found in P4 (44.32, medium category). Further analysis indicated that P4 had higher total energy and fat, but lower carbohydrates, total sugar, and glycemic index. According to the Multiple Attribute Zeleny Method, the P4 formula was the best formula for all parameters.The most effective formula, containing brown rice, oyster mushrooms, and tempeh flour (P4), could be a beneficial option for improving the health of individuals with diabetes in the community.

Association of Renal Hyperfiltration with Incidence of New-Onset Diabetes Mellitus: A Nationwide Cohort Study.

Background and Objectives: While the connection between decreased kidney function and diabetes mellitus (DM) is commonly acknowledged, there is insufficient research examining the relationship between higher-than-normal estimated glomerular filtration rate (eGFR) and the incidence risk of new-onset DM. Our research aimed to explore the relationship between an eGFR and the incidence risk of new-onset DM in the Korean general population through a nationwide longitudinal study. Methods: This research employed the cohort records of the National Health Insurance Service in Korea, analyzing records from 2,294,358 individuals between the ages of 20 and 79 who underwent health check-ups between 2010 and 2011. The eGFR levels from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation were used to assess the renal function. New-onset DM was defined as two or more claims with the International Classification of Diseases-10 classification codes E10 to E14, being prescribed any medication for lowering blood glucose, or having a record of fasting plasma glucose levels of ≥126 mg/dL from a health examination after the index date. Results: The mean age of subjects was 47.34 ± 13.76 years. The 150,813 (6.57%) new-onset DM cases were identified over a median follow-up of 9.63 years. In the multivariable Cox regression analysis, in comparison with the 5th decile, the 10th (≥114.12 mL/min/1.73 m2) (hazard ratio (HR): 0.52, 95% confidence interval (CI) (0.50-0.54), p < 0.001) eGFR decile was significantly associated with a decreased incidence of new-onset DM. Moreover, eGFR >120 mL/min/1.73 m2 was associated with a reduced risk of new-onset DM (HR: 0.40, 95% CI (0.39-0.42), p < 0.001). These results were consistent regardless of the presence of impaired glucose tolerance, age, or obesity. Conclusion: Our study showed higher-than-normal eGFR levels were associated with a lower risk of incidence for new-onset DM regardless of the presence of impaired glucose tolerance, age, or obesity. In general population, higher-than-normal eGFR may be associated with a lower risk of incidence of new-onset DM.

Polysaccharides in Medicinal and Food Homologous Plants regulate intestinal flora to improve type 2 diabetes: Systematic review

BackgroundMedicinal and food homologous plants (MFHPs) which can improve Type 2 Diabetes Mellitus (T2DM) draw significant attention among the public due to their low toxicity and more safety. Polysaccharides, one of the various active components of MFHPs, are recognized as effective modulators of the intestinal flora. By altering the composition of intestinal flora and affecting their metabolic products, polysaccharides can improve T2DM, making them a central focus of anti-diabetic research. PurposeThe purpose of this study is to systematically review the mechanism by which polysaccharides from MFHPs (MFHPPs) regulate the composition of intestinal flora and its metabolic products to improve T2DM. MethodsThis study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and conducts a comprehensive search on the PubMed, Web of Science and Embase databases. All experimental articles published up to March 4, 2024, are included in the search. ResultsAmong the 5733 articles reviewed, 29 were selected, covering 22 different MFHPs. MFHPPs can improve T2DM, particularly in lowering blood glucose levels, with consistent results. MFHPPs can regulate the diversity of intestinal flora in T2DM animal models, primarily affecting four phyla: decreasing Firmicutes and Proteobacteria while increasing Bacteroidetes and Actinobacteriota. At the genus level, the improvement of T2DM by MFHPPs is associated with the modulation of 12 key genera: Allobaculum, Akkermansia, Bifidobacterium, Lactobacillus, Helicobacter, Halomonas, Olsenella, Oscillospira, Shigella, Escherichia-Shigella, Romboutsia and Bacteroides. At the molecular level, MFHPPs primarily act by modulating the intestinal flora to increase short-chain fatty acid levels, promote the secretion of glucagon-like peptide-1, influence the IGF1/PI3K/AKT signaling pathway, or the PI3K/AKT/GSK-3β pathway, to lower blood glucose levels. They may also improve T2DM by working in glucose metabolism through the "microbiota-gut-organ" axis. MFHPPs can also alleviate T2DM by mitigating inflammation and oxidative stress: MFHPPs regulate intestinal flora to reduce lipopolysaccharide "leakage" and enhance intestinal mucosal permeability to tackle the inflammation associated with T2DM; MFHPPs enhance the expression of oxidative stress-related enzymes to alleviate oxidative stress and improve T2DM. Lastly, from a metabolic pathway perspective, MFHPPs are primarily involved in the metabolism of amino acids and their derivatives, carbohydrate metabolism and glutathione metabolism. ConclusionMFHPPs can improve T2DM by enhancing the composition of intestinal flora, regulating its metabolic products to promote insulin secretion, inhibiting glucagon-like peptide secretion, facilitating glycogen synthesis, reducing inflammation levels and alleviating oxidative stress. Furthermore, MFHPPs demonstrate potential protective effects on critical organs such as the pancreas, liver, kidneys and heart. Therefore, MFHPPs demonstrate significant clinical potential. However, most studies can only indicate the potential of MFHPPs intervention in improving T2DM through the intestinal flora. The causality between MFHPPs regulating the intestinal flora and T2DM requires further investigation.

Ameliorative Effects of Essential Oils on Diabetes Mellitus: A Review.

Diabetes mellitus (DM) is a metabolic disorder and is responsible for the death of more than 4.2 million people in 2019. Synthetic drugs for DM like metformin have been reported to induce numerous complications and side effects. Reports suggested that essential plant oil has been used as an herbal remedy to lower blood glucose levels. Essential oils (EOs) are complex combinations of small molecules obtained from plants via the process of steam distillation and several solvents. EOs have already shown great efficacy as antimicrobials, anti-inflammatory, hepatoprotective, and anti-hypertensive. This review aims to summarize some potential EOs that have been reported to have anti-diabetic activity both in preclinical and clinical aspects while summarizing the probable mechanism of action. The authors went through a vast number of articles from various scientific databases like Google Scholar, PubMed, and Web of Science. It was found that EO from a total of 20 plants has been pre-clinically investigated to have anti-diabetic potential. Besides this, clinical studies have reported the antidiabetic efficacy of EOs from Nigella sativa and Cuminum cyminum at different concentrations. Bioactive phytoconstituents like carvacrol, thymol, α- pinene, via . obtained from EOs ameliorate DM by inhibiting α-GLUC, α-amylase, lipase enzymes and increasing GLUT-4 expression, AKT phosphorylation, via . Although fewer in number, EOs from plant sources have demonstrated significant efficacy in DM. Proper elucidation of the anti-diabetic efficacy of the EOs may open up new avenues for drug discovery and development subjected to clinical studies.

Yeast polysaccharides: The environmentally friendly polysaccharides with broad application potentials.

Yeast cell wall (YCW) polysaccharides, including β-glucans, mannans, chitins, and glycogens, can be extracted from the waste of beer industry. They are environmentally friendly, abundant, inexpensive raw materials, and have shown broad biological activities and application potentials. The exploitation of yeast polysaccharides is of great importance for environmental protection and resource utilization. This paper reviews the structural features and preparation of YCW polysaccharides. The solubility and emulsification of yeast polysaccharides and the properties of binding metal ions are presented. In addition, biological activities such as blood glucose and lipid lowering, immune regulation, antioxidant, promotion of intestinal health, and promotion of wound healing are proposed, highlighting the beneficial effects of yeast polysaccharides on human health. Through modification, the physical and chemical properties of yeast polysaccharides are changed, which emphasizes the promotion of their biological activities and properties. In addition, the food applications of yeast polysaccharides, including the food packaging film, emulsifier, thickening agent, and fat alternatives, are focused and discussed.

Asiaticoside ameliorates type 2 diabetes mellitus in rats by modulating carbohydrate metabolism and regulating insulin signaling

Objective: To evaluate the effect of asiaticoside on streptozotocin (STZ) and nicotinamide (NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats. Methods: Asiaticoside (50 and 100 mg/kg body weight) was administered to STZ-NAD-induced diabetic rats for 45 days, and its effects on hyperglycaemic, carbohydrate metabolic, and insulin signaling pathway markers were examined. Results: Asiaticoside increased insulin production, lowered blood glucose levels, and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase activities. Abnormalities in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase activity. Furthermore, asiaticoside upregulated the mRNA expressions of IRS-1, IRS-2, and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to normal. Conclusions: Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis, gluconeogenesis, and insulin signaling pathways.

Evaluations of the in vitro and in vivo antidiabetic activity of 70 % ethanolic fruit extracts of Rosa abyssinica

BackgroundDiabetes mellitus is becoming major health challenge with continually increasing burden. High costs of conventional medicines and numerous side effects associated with them, on the other hand, easy availability and accessibility of traditional herbal medicines calls upon experimental investigations to validate their effect on lowering blood glucose level. MethodsThe dried fruit of Rosa abyssinica was macerated with 70 % ethanol and the extract's in vitro antidiabetic activity was investigated using dinitrosalisylic acid method for alpha amylase inhibitory activity. Furthermore, the in vivo hypoglycemic and Antihyperglycemic effects of various doses of the extract (100, 200 and 400 mg/kg) was determined on normoglycemic, glucose loaded (1500 mg/kg) and Streptozotocine (180 mg/kg)-induced diabetic mice models. ResultsThe acute oral toxicity study revealed the plant showed no toxic effect on swiss albino mice at 2000 mg/kg. The in vitro alpha amylase inhibitory activity study showed that the extract has comparable IC50 value of 21.37 ± 4.252 μg/ml with the standard drug acarbose (IC50 value of 26.72 ± 3.59 μg/ml). On the other hand, in normal mice, none of the dose levels except at 400 mg/kg significantly reduces blood glucose level. This is in contrast to the oral glucose tolerance test, which the extract produced significant reduction at 60, 90 and 120 min following glucose challenge. The 70 % ethanolic fruit extracts of Rosa abyssinica also experienced profound antidiabetic activity in streptozotocin-induced diabetic model. In the single-dose study, both RAFE200 and RAFE400 demonstrated a significant (P˂0.05) reduction in blood glucose levels at 1, 2, 3, and 4 h. Similarly, in the repeated-dose study, RAFE200 and RAFE400 not only significantly reduced blood glucose levels but also produced a notable improvement in animal body weight. ConclusionThe 70 % ethanolic fruit extracts of Rosa abyssinica have shown significant in vitro alpha amylase inhibition effect and an in vivo blood glucose level lowering effects in diabetic mice.Therefore, this study supports the traditional use of Rosa abyssinica in the management of diabetes mellitus.

Potential Effect of Curcumin in Lowering Blood Glucose Level in Streptozotocin-Induced Diabetic Rats.

The prevalence of diabetes mellitus has significantly increased, with 537 million individuals living with diabetes in 2021. Curcumin, a natural compound present in turmeric, has anti-inflammatory and antioxidant properties that aid in controlling diabetes. Curcumin can lower blood glucose levels, increase pancreatic cell function, and reduce insulin resistance. The pathophysiology of diabetes involves oxidative stress and endoplasmic reticulum stress, which can lead to cell death. This study aimed to evaluate the antidiabetic activity of curcumin in rats by administering it for a month and evaluating pancreatic tissue histology. STZ-induced diabetic rats were fed a high-fat diet containing glibenclamide, 200 mg/kg body weight (BW) curcumin, 400 mg/kg BW curcumin, or a placebo for 4 weeks. After intervention, blood glucose levels were measured, and the pancreatic tissue was examined. Blood glucose levels were measured at 0, 2, 4, 6, and 8 h. One-way ANOVA was performed to measure the mean difference among the groups at 0, 2, 4, 6, and 8 h of observation, which reported a statistically significant difference (p < 0.05). The blood glucose levels decreased after 4 h in the group receiving curcumin. Histological evaluation of the pancreas showed slight hydropic degeneration after 4 weeks of curcumin treatment. Our study indicates that curcumin has a beneficial effect in diabetic rats by reducing blood glucose levels and a protective effect on the pancreas.

Effects of vitamin D supplementation on diabetic foot ulcer healing: a meta-analysis.

To systematically review the effect of vitamin D supplementation on diabetic foot ulcer (DFU) healing. The PubMed, Web of Science, Science direct, Ebsco host, CNKI, WanFang, VIP, and CBM databases were electronically searched to collect randomized controlled trials (RCTs) on the impact of vitamin D supplementation on DFUs from inception to 19 November 2022. Two researchers independently screened the literature, extracted the data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.3 software. A total of seven studies involving 580 patients were included. The results of meta-analysis showed that compared with control group, the wound healing efficiency rate (RR = 1.42, 95%CI 1.03 to 1.95, P= 0.03) and wound reduction rate (MD = 13.11, 95%CI 4.65 to 21.56, P < 0.01) of the experimental group were higher; the change values of the wound area (MD = -3.29, 95%CI -4.89 to 1.70, P < 0.01) and 25 (OH) D (MD = 9.63, 95%CI 6.96 to 12.31, P < 0.01) were larger. Supplementation of vitamin D on DFU patients can improve glucose metabolism and insulin indexes: hemoglobin A1c (MD = -0.44, 95%CI -0.62 to -0.26, P < 0.01), fasting insulin (MD = -3.75, 95%CI -5.83 to -1.67, P < 0.01), HOMA - β (MD = -5.14, 95%CI -8.74 to -1.54, P < 0.01), and quantitative insulin sensitivity check index (MD = 0.02, 95%CI 0.01 to 0.02, P < 0.01). It can also improve inflammation and oxidative stress markers: high sensitivity C-reactive protein (MD = -0.83, 95%CI -1.06 to -0.59, P < 0.01), erythrocyte sedimentation rate (MD = -15.74, 95%CI -21.78 to -9.71, P<0.01), nitric oxide (MD = 1.81, 95%CI 0.07 to 3.55, P= 0.04), and malondialdehyde (MD = -0.43, 95%CI -0.61 to -0.24, P<0.01). There was no statistically significant difference in changes of fasting plasma glucose, homeostasis model of assessment-insulin resistance, total antioxidant capacity, glutathione, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol (P>0.05). The current evidence suggests that vitamin D supplementation can significantly promote DFU healing by lowering blood sugar and alleviating inflammation and oxidative stress. Key messages What is already known on this topic Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus, with high morbidity, mortality and resource utilization. Vitamin D has the effect of lowering blood sugar, improving insulin sensitivity, and increasing anti-inflammatory response. Clinical research on vitamin D supplementation for the treatment of DFU is increasing, but due to the lack of combing and integration, the actual efficacy of vitamin D in patients is unclear. What this study adds This meta-analysis has shown that vitamin D supplementation can significantly promote DFU healing by lowering blood glucose and alleviating inflammation and oxidative stress. How this study might affect research, practice or policy This study preliminarily found the effectiveness of vitamin D supplementation on the healing of DFU, which can provide a reference for the treatment of DFU by medical staff.

Comparison of the effects of Liraglutide, Tirzepatide, and Retatrutide on diabetic kidney disease in db/db mice.

To assess and compare the therapeutic efficacy of Liraglutide, Tirzepatide, and Retatrutide in treating diabetic kidney disease (DKD) in db/db mice. Db/db mice were administered intraperitoneal injections of Liraglutide (10 nmol/kg), Tirzepatide (10 nmol/kg), and Retatrutide (10 nmol/kg) for 10 weeks. Subsequently, we assessed the effectiveness of these three drugs in controlling blood glucose levels, reducing weight, and improving serum biochemical indicators and DKD. Additionally, we measured and compared the renal inflammation and fibrosis indexes. Meanwhile, the content of intestinal metabolite butyrate was compared to reflect the regulatory effects of these three drugs on gut microbiota. Retatrutide demonstrated superior effectiveness in reducing weight and improving renal function in db/db mice compared to Liraglutide and Tirzepatide. Additionally, it markedly suppressed the expression of pro-inflammatory cytokines (TNF-α, caspase-1, and NLRP3) and pro-fibrotic factors (fibronectin, α-SMA, and collagen I) in the kidneys of mice. Furthermore, Retatrutide substantially enhanced liver function, reduced triglyceride levels, cholesterol levels, low-density lipoprotein cholesterol, elevated high-density lipoprotein cholesterol, and increased the content of intestinal metabolite butyrate in db/db mice when compared to the other two drugs. Unfortunately, despite its ability to lower blood glucose levels, Retatrutide did not outperform the other two drugs. In contrast, Tirzepatide exhibited better effects on lowering blood glucose, weight loss, lipid reduction, and improvement of DKD compared to Liraglutide. Retatrutide and Tirzepatide were significantly effective in improving DKD, controlling blood glucose and body weight. Retatrutide was the most effective in improving DKD and body weight, while Tirzepatide was the most effective in controlling blood glucose. Inhibiting the expression of inflammatory factors and fibrosis mediators and regulating intestinal microbiota may be the potential mechanisms of these two drugs to delay the progression of DKD.

Preliminary Study on Pulse-Based Snack “Vadai” Reducing Postprandial Glycaemic Response in Healthy Malaysian Adults

Snack consumption contributes significantly to daily energy and nutrient intake. Low glycaemic index (GI) and glycaemic load (GL) snacks help modulate postprandial glucose (PPG) rise in prediabetes and diabetes. Masala Vadai (MS) and Medu Vadai (MD) are traditional Indian snacks made from pulses, where their GI and GL values and the effect on PPG remain unexplored. In this randomised cross-over trial, healthy adults (n=13, 19-30 years old, 22.3±2.3 kg/m2) consumed either MS, MD, or glucose solution as reference food (RF) containing 12.5g of available carbohydrate on three occasions with one week apart between each test. Capillary blood was measured at 0, 15, 30, 45, 60, 90, and 120 minutes to calculate incremental area under the curve (iAUC) and to estimate the GI. The results showed that when compared to RF, MD but not MS had significantly lower iAUC at 30-min (p=0.013) and 45-min (p=0.001). Both snacks had low peak blood glucose (p&lt;0.001) and incremental peak blood glucose (p&lt;0.001), wherein MD exhibited a more delayed effect than MS. However, time to peak blood glucose did not differ between the test foods and RF. MD and MS had low-medium GI (MD=47, MS=63) and low GL (MD=6, MS=8), respectively. In conclusion, MD attenuated PPG significantly more than MS in comparison to glucose solution, offering an advantage of glycaemic control. Even within similar pulse-based snacks, the GI value is important in influencing PPG. These findings will add to the GI compendium for Asian foods and will be useful to healthcare professionals in providing sound nutritional advice.

The Role and Mechanism of Probiotics Supplementation in Blood Glucose Regulation: A Review.

With economic growth and improved living standards, the incidence of metabolic diseases such as diabetes mellitus caused by over-nutrition has risen sharply worldwide. Elevated blood glucose and complications in patients seriously affect the quality of life and increase the economic burden. There are limitations and side effects of current hypoglycemic drugs, while probiotics, which are safe, economical, and effective, have good application prospects in disease prevention and remodeling of intestinal microecological health and are gradually becoming a research hotspot for diabetes prevention and treatment, capable of lowering blood glucose and alleviating complications, among other things. Probiotic supplementation is a microbiologically based approach to the treatment of type 2 diabetes mellitus (T2DM), which can achieve anti-diabetic efficacy through the regulation of different tissues and metabolic pathways. In this study, we summarize recent findings that probiotic intake can achieve blood glucose regulation by modulating intestinal flora, decreasing chronic low-grade inflammation, modulating glucagon-like peptide-1 (GLP-1), decreasing oxidative stress, ameliorating insulin resistance, and increasing short-chain fatty acids (SCFAs) content. Moreover, the mechanism, application, development prospect, and challenges of probiotics regulating blood glucose were discussed to provide theoretical references and a guiding basis for the development of probiotic preparations and related functional foods regulating blood glucose.

Astragaloside IV attenuates fatty acid-induced renal tubular injury in diabetic kidney disease by inhibiting fatty acid transport protein-2

BackgroundRenal tubular injury induced by free fatty acid bound to albumin is the key pathological basis for the progression of diabetic kidney disease. However, effective interventions are limited. Astragaloside IV, as a major bioactive component purified from Astragalus membranaceus (Fisch.) Bunge, possesses pharmacological properties of lowering blood glucose and proteinuria, and renal tubular protection in diabetic kidney disease. Further work is needed to understand the underlying molecular mechanisms. PurposeThis study was designed to investigate the mechanism of renal tubular protection by astragaloside IV in diabetic kidney disease. MethodsRats receiving high-fat diet combined with streptozotocin (30 mg/kg, i.p.) were gavaged with astragaloside IV (10 mg/kg/d or 20 mg/kg/d) or empagliflozin (1.72 mg/kg/d) for 8 weeks. In vitro, the NRK-52E cells were treated with free fatty acid-deleted BSA or palmitic acid-bound BSA in the presence or absence of astragaloside IV (5 μM, 10 μM, 20 μM) or 5 μM of mcc950. The effects of astragaloside IV on mitochondrial function, NLRP3/ASC/IL-18/IL-1β inflammatory cascade, and renal tubular injury were detected by pathological staining, immunoblotting, MitoSOX Red staining. Next, to investigate the mechanism of renal tubular protection by astragaloside IV, we transfected Fatp2 siRNA into BSA-PA-treated NRK-52E cells and injected lipofermata (a FATP2 inhibitor) intraperitoneally into free fatty acid-bound BSA overloaded rats with concomitant astragaloside IV treatment. ResultsTreatment with astragaloside IV for 8 weeks dose-dependently attenuated the blood glucose, ratio of urinary albumin to creatinine, disorder of lipid metabolism, and pathological injury in diabetic kidney disease rats. In addition, astragaloside IV dose-dependently attenuated mitochondrial-derived reactive oxygen species and subsequent inhibiting NLRP3-mediated inflammatory cascade in diabetic kidney disease rats and palmitic acid-bound BSA-treated NRK-52E cells, thereby exerting renal tubular protection. More importantly, the effects of astragaloside IV on restoration of mitochondrial function, inhibition of inflammatory response and amelioration of renal tubular injury in vivo and in vitro were further enhanced when used in combination with Fatp2 siRNA or lipofermata. ConclusionAstragaloside IV exerts antioxidant and anti-inflammatory effects in diabetic kidney disease by inhibiting FATP2-mediated fatty acid transport, thereby attenuating renal tubular injury.

Ketone monoester attenuates declines in cognitive performance and oxygen saturation during acute severe hypoxic exposure under resting conditions.

Exogenous ketone supplements are a potential augmentation strategy for cognitive resilience during acute hypoxic exposure due to their capacity to attenuate the decline in oxygen (O2) availability, and by providing an alternative substrate for cerebral metabolism. Utilizing a single-blind randomized crossover design, 16 male military personnel (age, 25.3±2.4year, body mass, 86.2±9.3kg) performed tests of cognitive performance at rest in three environments: room air (baseline), normoxia (20min; 0m; 20.9% O2) and hypoxia (20min; 6096m, 9.7% O2) using a reduced O2 breathing device (ROBD). (R)-3-Hydroxybutyl (R)-3-hydroxybutyrate (R-BD R-βHB) ketone monoester (KME; 650mg/kg, split dose given at 30min prior to each exposure) or taste-matched placebo (PLA) was ingested prior to normoxia and hypoxic exposure. Blood R-βHB and glucose concentrations, cognitive performance and O2 saturation ( ) were collected throughout. KME ingestion increased blood R-βHB concentration, which was rapid and sustained (>4mM 30min post; P<0.001) and accompanied by lower blood glucose concentration (∼20mg/dL; P<0.01) compared to PLA. Declines in cognitive performance during hypoxic exposure, assessed as cognitive efficiency during a Defense Automated Neurobehavioral Assessment (DANA) code substitution task, were attenuated with KME leading to 6.8 (95% CL: 1.0, 12.6) more correct responses per minute compared to PLA (P=0.018). The decline in during hypoxic exposure was attenuated (6.40% ; 95% CL: 0.04, 12.75; P=0.049) in KME compared to PLA (KME, 76.8±6.4% ; PLA, 70.4±7.4% ). Acute ingestion of KME attenuated the decline in cognitive performance during acute severe hypoxic exposure, which coincided with attenuation of declines in O2 saturation.

Assessing the potential fasting and postprandial mechanisms involved in the acute hypoglycemic and anti-hyperglycemic effects of four selected plants from Iran used in traditional Persian medicine

Ethnopharmacological relevanceIn traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear.Aim of the study: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. Materials and methodsThe effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. ResultsIn the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90–97% and 80–91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. ConclusionsThe present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

Blood glucose and β-hydroxybutyrate predict significant brain injury after hypoxia-ischemia in neonatal mice.

The Vannucci procedure is widely used to model cerebral hypoxic-ischemic (HI) injury in neonatal rodents. Identifying minimally invasive biomarkers linked to brain injury would improve stratification of pups to experimental treatments. We hypothesized that extreme blood glucose (BG) and β-hydroxybutyrate (bHB) levels immediately after HI will correlate with severity of brain injury in this model. C57BL6 mice of both sexes underwent the Vannucci procedure with BG and bHB measured immediately after hypoxia. GFAP and α-fodrin were measured to assess injury severity at 4h, P11, P18 and P40. Open field (OF), Y-maze (YM), and Object-location task (OLT) were tested at P40. Clinical seizures-like stereotypies during hypoxia were associated with lower post-hypoxia BG in HI-injured mice. Low BG after HI was related to higher GFAP expression, higher α-fodrin breakdown, lower residual regional volume, and worse working memory. BG was superior to bHB in ROC analysis with BG threshold of <111 mg/dL providing 100% specificity with 72% sensitivityfor hippocampal HI-injury. Post-hypoxic BG is a minimally invasive screening tool to identify pups with significant HI brain injury in the Vannucci model modified for mice improving our ability to stratify pups to experimental treatments to assess effectiveness. End hypoxic-ischemic blood glucose levels are a reliable and inexpensive biomarker to detect hypoxic-ischemic brain injury in mice. Screening with blood glucose levels post-hypoxia allows appropriate stratification of those mouse pups most likely to be injured to experimental treatments improving validity and translatability of the results. These findings provide biological plausibility to the clinical observation that extreme blood glucose levels relate to worse outcomes after hypoxia-ischemia.

Purification and Identification of Novel Dipeptidyl Peptidase IV Inhibitory Peptides Derived from Bighead Carp (Hypophthalmichthys nobilis).

Dipeptidyl peptidase IV (DPP-IV) inhibitors are widely used in treating type 2 diabetes due to their ability to lower blood glucose levels. However, synthetic versions often lead to gastrointestinal side effects. This study explores DPP-IV inhibitory properties in peptides from bighead carp skin. Collagen was prepared, hydrolyzed into collagen peptides, and then fractionated for DPP-IV inhibitory activity examination. The most effective fractions were identified, and their peptide sequences were determined. Molecular docking analysis identified nine peptides with potential inhibitory activity, four of which (VYP, FVA, PPGF, PGLVG) were synthesized and tested in vitro. PPGF exhibited the highest potency with an IC50 of 4.63 nM, competitively binding to key DPP-IV sites, including ARG125, VAL711, TYR666, and TYR662. Other peptides showed varying effectiveness, with IC50 values of 398.87 nM (VYP), 402.02 nM (FVA), and 110.20 nM (PGLVG). These findings highlight bighead carp skin peptides as potent DPP-IV inhibitors with hypoglycemic potential, suggesting a novel avenue for diabetes management using natural peptides. Moreover, this research underscores the utilization of bighead carp by-products, contributing to environmental sustainability.

Potatoes Compared with Rice in Meals with either Animal or Plant Protein Reduce Postprandial Glycemia and Increase Satiety in Healthy Adults: A Randomized Crossover Study

BackgroundRice and pasta are recommended as healthier than potatoes on the basis of their glycemic index when eaten alone. ObjectivesThe study objective was to evaluate postprandial glycemia (PPG), appetite, and food intake (FI) at meals with potatoes or rice when consumed with either meatballs or their vegetarian substitute. MethodsIn a randomized, single-blinded, crossover design, 26 (13 males and 13 females) healthy adults (age: 18–45 y; body mass index [kg/m2]: 18.5–29.9) consumed isocaloric fixed amounts of either meatballs or vegetarian-substitute balls with ad libitum access to either baked French fries (BFF), instant mashed potatoes (IMPs), or rice (control). FI was measured at the meal and at an ad libitum pizza meal served 120 min later. Blood glucose (BG), appetite, and plasma insulin responses were measured within the meal (0–30 min), postmeal (30–120 min), within pizza meal (120–140 min), and post-pizza (140–170 min). Effects of protein source, carbohydrate (CHO) source, and sex and their interactions were analyzed using analysis of variance followed by Tukey’s post hoc test. ResultsParticipants consumed 23–25% less treatment meal energy (kcal), 32–34% less CHO energy (kcal), and 13–16% less total energy (kcal) after the BFF and IMP than rice meals (P < 0.0001). Postmeal BG was lower after IMP (6.76 ± 0.15; P < 0.0001) and rice (6.92 ± 0.15; P = 0.0012) compared with BFF (7.19 ± 0.15). Post-pizza BG was higher after rice (6.77 ± 0.09) than that after BFF (6.51 ± 0.09; P = 0.0012) and IMP (6.39 ± 0.09; P < 0.0001). Postmeal meaned insulin was higher after BFF (82.16 ± 8.58) and IMP (77.75 ± 8.60) compared with rice (56.44 ± 8.59; P < 0.002). Insulin during pizza meal was lower after BFF (17.14 ± 6.90) compared with both IMP (39.03 ± 6.90; P = 0.0060) and rice (34.21 ± 6.90; P = 0.0336). Meatballs led to lower BG (6.48 ± 0.09; P = 0.0076) and higher insulin (84.54 ± 5.87; P = 0.0406) post-pizza compared with their plant protein substitute (6.64 ± 0.09 and 73.18 ± 5.87, respectively). ConclusionsAdults consuming meatballs or plant-based substitute with ad libitum IMP had lower PPG post-treatment and at a later pizza meal compared with rice. Both IMP and BFF resulted in lower energy intake than after rice.This trial was registered at http://clinicaltrials.gov (https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000CKIJ&selectaction=Edit&uid=U0000IA4&ts=2&cx=-uf51kf) as NCT05610124. Protocol ID: 43406 (Postprandial Glycemia and Satiety of Meals with Potatoes, with and without Protein).

Mechanism of Takifugu bimaculatus Skin Peptides in Alleviating Hyperglycemia in Rats with Type 2 Diabetic Mellitus Based on Microbiome and Metabolome Analyses.

In this study, we aimed to explore the hypoglycemic effects of a hydrolysate on Takifugu bimaculatus skin (TBSH). The effect of the dipeptidyl peptidase-IV (DPP-IV) inhibitory activities from different TBSH fractions was investigated on basic indexes, gut hormones, blood lipid indexes, viscera, and the gut microbiota and its metabolites in rats with type 2 diabetes mellitus (T2DM). The results showed that the <1 kDa peptide fraction from TBSH (TBP) exhibited a more potent DPP-IV inhibitory effect (IC50 = 0.45 ± 0.01 mg/mL). T2DM rats were induced with streptozocin, followed by the administration of TBP. The 200 mg/kg TBP mitigated weight loss, lowered fasting blood glucose levels, and increased insulin secretion by 20.47%, 25.23%, and 34.55%, respectively, rectified irregular hormonal fluctuations, lipid metabolism, and tissue injuries, and effectively remedied gut microbiota imbalance. In conclusion, TBP exerts a hypoglycemic effect in rats with T2DM. This study offers the potential to develop nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus. It will provide information for developing nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus.

Berberine hydrochloride-loaded lipid-based nanoparticles ameliorate β-cell function by targeting Nrf2/NF-κB signaling pathway in alloxan-induced diabetes using a murine model: Optimization through full factorial design

Berberine hydrochloride (BH), a naturally occurring alkaloid having pleiotropic biological effects, is characterized by high water solubility, poor bioavailability, and a brief half-life. The objective of this study was to develop a liposomal formulation of BH that is more accessible and to ascertain whether its intraperitoneal administration might mitigate pancreatic tissue damage in rats that have been induced by alloxan. Rats were divided into four groups: control, alloxan, metformin, and BH-liposomes (BH-Lip). Measurements of blood glucose, insulin, pancreatic antioxidant state, and pro-inflammatory mediators were used to assess the severity of pancreatic injury in rats among all groups. According to the results, BH-Lip reduced the extent of alloxan-induced pancreatic tissue damage in rats, as demonstrated by improved HOMA-IR and HOMA-β scores, insulin, total pancreatic antioxidant capacity, and lower blood glucose levels. Furthermore, BH-Lip boosted the antioxidant transcription factor Nrf2 and downregulated the mRNA expression of pancreatic pro-inflammatory mediators, such as NF-κB and NLRP3. Moreover, immuno-histochemical labeling revealed that BH-Lip inhibited the protein transcription of caspase-3 and TNF-α in the pancreatic tissues of alloxan-treated rats. These findings provide BH-Lip as a safe substitute for traditional antidiabetics by reducing pancreatic tissue damage caused by alloxan via targeting the Nrf2/NF-κB pathway.