Reduction In Glucose Research Articles

Effects of chronic inspiratory muscle strength training on metabolic and cardiovascular measures during a glucose tolerance test

Previous work has shown that both a single session of aerobic exercise and chronic exercise training improve glucose homeostasis. Similarly, a single bout of inspiratory muscle strength training (IMST) has been shown to facilitate a greater degree of glycemic control. However, less is known about the chronic effects of IMST, particularly with respect to metabolic and cardiovascular responses to an oral glucose tolerance test (OGTT). We hypothesized that 6 weeks of IMST would promote a greater degree of glycemic control, via a reduction in fasting and peak glucose during an OGTT. To test this hypothesis, participants (n=14, 57% female, average age=21.9) completed 6 weeks of daily training at either 15% (n=7) or 75% (n=7) of their maximal inspiratory pressure. Each subject underwent a pre-IMST glucose tolerance test in which their blood glucose level, blood pressure, and heart rate were measured at baseline, 15, 30, 45, 60, and 90 minutes following glucose ingestion. A post-IMST glucose tolerance test was completed after 6 weeks of training. The results indicate no training effect on baseline glucose, peak glucose, 90-minutes post-glucose, or glucose area under the curve responses, for both training intensities (P>0.05). There was no significant effect of IMST on heart rate, nor was heart rate altered during the OGTT (P>0.5). While mean arterial pressure was not affected during the OGTT (P>0.05), baseline mean arterial pressure decreased in the 75% intensity group only (P=0.012). In summary, 6 weeks of high-intensity IMST decreases baseline blood pressure, and glucose tolerance was unaffected in both training groups. Future studies should investigate the effects of chronic IMST on other metabolic measures (e.g. lipids, triglycerides, and/or cholesterol levels) and the impact that this training has on glucose homeostasis in clinical populations. This work was supported by the Alma College CORE Summer Research Program. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

One-step hydrothermal synthesis of vanadium dioxide/carbon core–shell composite with improved ammonium ion storage for aqueous ammonium-ion battery

Aqueous nonmetallic ion batteries have garnered significant interest due to their cost-effectiveness, environmental sustainability, and inherent safety features. Specifically, ammonium ion (NH4+) as a charge carrier has garnered more and more attention recently. However, one of the persistent challenges is enhancing the electrochemical properties of vanadium dioxide (VO2) with a tunnel structure, which serves as a highly efficient NH4+ (de)intercalation host material. Herein, a novel architecture, wherein carbon-coated VO2 nanobelts (VO2@C) with a core–shell structure are engineered to augment NH4+ storage capabilities of VO2. In detail, VO2@C is synthesized via the glucose reduction of vanadium pentoxide under hydrothermal conditions. Experimental results manifest that the introduction of the carbon layer on VO2 nanobelts can enhance mass transfer, ion transport and electrochemical kinetics, thereby culminating in the improved NH4+ storage efficiency. VO2@C core–shell composite exhibits a remarkable specific capacity of ∼300 mAh/g at 0.1 A/g, which is superior to that of VO2 (∼238 mAh/g) and various other electrode materials used for NH4+ storage. The NH4+ storage mechanism can be elucidated by the reversible NH4+ (de)intercalation within the tunnel of VO2, facilitated by the dynamic formation and dissociation of hydrogen bonds. Furthermore, when integrated into a full battery with polyaniline (PANI) cathode, the VO2@C//PANI full battery demonstrates robust electrochemical performances, including a specific capacity of ∼185 mAh·g−1 at 0.2 A·g−1, remarkable durability of 93 % retention after 1500 cycles, as well as high energy density of 58 Wh·kg−1 at 5354 W·kg−1. This work provides a pioneering approach to design and explore composite materials for efficient NH4+ storage, offering significant implications for future battery technology enhancements.

Cinnamon oil-based self-emulsifying system for augmented dissolution and hypoglycemic efficacy of gliquidone

The aim was to formulate self-emulsifying drug delivery systems (SEDDS) to hasten dissolution and oral bioavailability of gliquidone (GLQ) as lipophilic oral hypoglycemic. In the developed formulations, cinnamon oil served as the oily phase, while Tween 20 and Transcutol® HP constituted the surfactant/cosurfactant system. A phase diagram was employed to select formulations showing transparent/translucent system after dispersion. These formulations were loaded with GLQ and subjected to in vitro dissolution studies relative to unprocessed GLQ. Optimum systems providing the fastest release were characterized for globule size and morphology. In addition, the in vivo hypoglycemic effect GLQ-loaded SEDDSs was assessed after oral administration to diabetic rats relative to GLQ aqueous dispersion (control). Optimized GLQ-loaded SEDDSs (3 formulations) displayed a significant improvement of dissolution rate as indicated from the amount dissolved after 5 min which recorded 72.83 %, 83.34 % and 92.38 %. Fast dissolution was parallel correlated with globule size values which were 335.4, 211.8 and 175.8 nm for the same formulations, respectively. Ultrafast dispersion and dissolution were revealed further in the in vivo hypoglycemic effect which was shown increasing the area under blood glucose reduction curve by 1.58, 1.61 and 2.11-fold after administration of the same formulation, compared with the control, respectively. Overall, the developed SEDDSs successfully enhanced both the dissolution rate and the bioavailability of GLQ.

Morphological and Biochemical Characterization of Strains of Ralstonia solanacearum, Causal Agent of Bacterial Wilt in Tomatoes in Cameroon and Screening of Virulent Strains

Ralstonia solanacearum is a major constraint in tomato production. The aim of this work was to identify the different biovars and races of R. solanacearum which infect tomato plants in Cameroon and determine the most virulent in a gnotobiotic environment. Thirty (30) samples were collected in the field of 03 different agro-ecological zones considered as major tomato production area in Cameroon. The bacteria were isolated on modified Kelman solid medium, and identified based on morphological and biochemical characterization. The pathogenicity test was performed in a gnotobiotic environment by root inoculation. Twenty-nine (29) isolates showed colonies characteristic of virulent strains. Water, motility, catalase, KOH, Kovac oxidase, glucose reduction, and sucrose tests were positive. However, gram staining, spore production, arginine test and sulfate reduction were negative. The biovar tests carried out revealed the presence16.66% biovar 2 (bv 2) and 76.66% biovar 3(bv 3). The tobacco hypersensitivity tests carried out revealed the presence of two (02) races: race 1 and race 3 (majority). A predominance of race3 biovar 3 was observed in Cameroon. Results from pathogenicity test revealed that two (02) strains, FM6 (race 3 bv2) and BFo (race 3 bv 3) were high virulent, causing up to 100% loss of seedlings on the sixth day post-inoculation.

Continuous glucose monitoring for glycaemic control and cardiovascular risk reduction in patients with type 2 diabetes not on insulin therapy: A clinical trial.

To evaluate the impact of the Dexcom G6 continuous glucose monitoring (CGM) device on glycaemic control and cardiometabolic risk in patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk who are not on insulin therapy. Adults with T2DM with glycated haemoglobin (HbA1c) >7% and body mass index (BMI) ≥30 kg/m2 not using insulin were enrolled in a two-phase cross-over study. In phase 1, CGM data were blinded, and participants performed standard glucose self-monitoring. In phase 2, the CGM data were unblinded, and CGM, demographic and cardiovascular risk factor data were collected through 90 days of follow-up and compared using paired tests. Forty-seven participants were included (44% women; 34% Black; mean age 63 years; BMI 37 kg/m2; HbA1c 8.4%; 10-year predicted atherosclerotic cardiovascular disease risk 24.0%). CGM use was associated with a reduction in average glucose (184.0 to 147.2 mg/dl, p < .001), an increase in time in range (57.8 to 82.8%, p < .001) and a trend towards lower glucose variability (26.2 to 23.8%). There were significant reductions in HbA1c, BMI, triglycerides, blood pressure, total cholesterol, diabetes distress and 10-year predicted risk for atherosclerotic cardiovascular disease (p < .05 for all) and an increase in prescriptions for sodium-glucose cotransporter 2 inhibitors (36.2 to 83.0%) and glucagon-like peptide-1 receptor agonists (42.5 to 87.2%, p < .001 for both). Dexcom G6 CGM was associated with improved glycaemic control and cardiometabolic risk in patients with T2DM who were not on insulin. CGM can be a safe and effective tool to improve diabetes management in patients at high risk for adverse cardiovascular outcomes.

Short-term effects of obesity surgery versus low-energy diet on body composition and tissue-specific glucose uptake: a randomised clinical study using whole-body integrated 18F-FDG-PET/MRI

Aims/hypothesisObesity surgery (OS) and diet-induced weight loss rapidly improve insulin resistance. We aim to investigate the impact of either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with a diet low in energy (low-calorie diet; LCD) on body composition, glucose control and insulin sensitivity, assessed both at the global and tissue-specific level in individuals with obesity but not diabetes.MethodsIn this parallel group randomised controlled trial, patients on a waiting list for OS were randomised (no blinding, sealed envelopes) to either undergo surgery directly or undergo an LCD before surgery. At baseline and 4 weeks after surgery (n=15, 11 RYGB and 4 SG) or 4 weeks after the start of LCD (n=9), investigations were carried out, including an OGTT and hyperinsulinaemic–euglycaemic clamps during which concomitant simultaneous whole-body [18F]fluorodeoxyglucose-positron emission tomography (PET)/MRI was performed. The primary outcome was HOMA-IR change.ResultsOne month after bariatric surgery and initiation of LCD, both treatments induced similar reductions in body weight (mean ± SD: −7.7±1.4 kg and −7.4±2.2 kg, respectively), adipose tissue volume (7%) and liver fat content (2% units). HOMA-IR, a main endpoint, was significantly reduced following OS (−26.3% [95% CI −49.5, −3.0], p=0.009) and non-significantly following LCD (−20.9% [95% CI −58.2, 16.5). For both groups, there were similar reductions in triglycerides and LDL-cholesterol. Fasting plasma glucose and insulin were also significantly reduced only following OS. There was an increase in glucose AUC in response to an OGTT in the OS group (by 20%) but not in the LCD group. During hyperinsulinaemia, only the OS group showed a significantly increased PET-derived glucose uptake rate in skeletal muscle but a reduced uptake in the heart and abdominal adipose tissue. Both liver and brain glucose uptake rates were unchanged after surgery or LCD. Whole-body glucose disposal and endogenous glucose production were not significantly affected.Conclusions/interpretationThe short-term metabolic effects seen 4 weeks after OS are not explained by loss of body fat alone. Thus OS, but not LCD, led to reductions in fasting plasma glucose and insulin resistance as well as to distinct changes in insulin-stimulated glucose fluxes to different tissues. Such effects may contribute to the prevention or reversal of type 2 diabetes following OS. Moreover, the full effects on whole-body insulin resistance and plasma glucose require a longer time than 4 weeks.Trial registrationClinicalTrials.gov NCT02988011FundingThis work was supported by AstraZeneca R&D, the Swedish Diabetes Foundation, the European Union’s Horizon Europe Research project PAS GRAS, the European Commission via the Marie Sklodowska Curie Innovative Training Network TREATMENT, EXODIAB, the Family Ernfors Foundation, the P.O. Zetterling Foundation, Novo Nordisk Foundation, the Agnes and Mac Rudberg Foundation and the Uppsala University Hospital ALF grantsGraphical

Structural Properties and Photocatalytic Activity of TiO2/Au Nanocomposites Synthesized with Glucose

AbstractA one‐pot synthesis of plasmonic gold‐modified TiO2 nanocomposites is reported by using glucose reduction of HAuCl4 in presence of titanium tetraisopropoxide. The resulting nanocomposites are characterized by thermal‐gravimetric analyses, X‐ray diffraction combined with X‐ray fluorescence and photoelectron spectroscopies. A binary system of β‐TiO2 and anatase phases is obtained for low Au content while only anatase form is favored when the initial Au rate rises. This investigation also suggests the inclusion of gold in the TiO2 structure. Although the optical bandgap of the different nanocomposites remains around 3 eV, the increase of Au content induces a shift of both valence and conduction edge bands to lower energy levels. The photocatalytic activity of TiO2/Au nanocomposites is assessed through the decolorization of different cationic and anionic dyes as model compounds. Regarding rhodamine and methylene blue dyes, the sample TiO2 modified with 3.5 wt% of Au presents the best performance. The relation between the structure of the nanocomposites and their capacity to degrade pollutants is discussed.

Impact of Nicotine Exposure and Withdrawal on Plasma Glucose, Insulin and Glycated Haemoglobin in High-Fat Diet Fed Wistar Rats

Background to the study: Nicotine, which is the most abundant constituent of tobacco cigarette is one of the most commonly abused drugs. The duo of obesity and tobacco smoking increases the risk of cardiometabolic disorders. Methodology: The experiment involved 48 male wistar rats separated into 4 groups of 8 rats each. All the animals were placed on high-fat diet (Margarine; blue band) in addition to the different doses of nicotine in the experimental groups. Group 1 served as control and received distilled water, Groups 2, 3 and 4 received 200µg/kg, 400µg/kg and 800µg/kg of nicotine oral solution respectively. The experimental groups were placed on their respective doses of nicotine solution for an initial four weeks. Thereafter, four animals in each group were sacrificed and blood samples collected to determine their nicotine exposure plasma levels of glucose, insulin and glycated hemoglobin. The remaining four animals in each group continued without nicotine for another four weeks after which they were sacrificed and blood samples collected to determine their nicotine withdrawal plasma levels of glucose, insulin and glycated hemoglobin. Results: The results showed that exposure to the three concentrations of nicotine (200, 400 and 800µg/kg respectively) significantly caused a rise in plasma insulin levels but dose-dependent reduction in both glucose and glycated haemoglobin compared to their control groups. Four weeks after withdrawal of initial 200µg/kg nicotine there were no significant changes in the levels of plasma glucose, insulin and glycated haemoglobin compared to the nicotine exposed groups. Withdrawal, after initial exposure to 400µg/kg of nicotine was associated with significant rise in both the plasma glucose and glycated haemoglobin but no significant change in insulin compared to their respective nicotine exposed groups. Cessation, after initial exposure 800µg/kg of nicotine resulted in significant rise in plasma levels of glucose, ..........

Synergistic effects of Metformin and Forskolin on oxidative stress induced by diabetes and hepatocellular cancer: An animal study

AimThis study proposed to assess the synergistic effects of Forskolin and Metformin (alone and in combination) on glucose, hematological, liver serum, and oxidative stress parameters in diabetic, healthy, and hepatocellular carcinoma (HCC) induced rats. Materials and methodsEighty male Wistar rats were divided into 10 experimental groups (8 rats for each group), including 1) healthy group, 2) diabetic group, 3) HCC group, 4) diabet + Metformin (300 mg/kg), 5) diabet + Forskolin (100 mg/kg), 6) diabet + Metformin (300 mg/kg) & Forskolin (100 mg/kg), 7) HCC + Metformin (300 mg/kg), 8) HCC + Forskolin (100 mg/kg), 9) HCC + Metformin (300 mg/kg) & Forskolin (100 mg/kg), and 10) healthy group + Metformin (300 mg/kg) & Forskolin (100 mg/kg). The rats were administrated Forskolin/Metformin daily for 8 weeks. Glucose, hematological, and liver serum parameters were measured and compared among the groups. The levels of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as 8-hydroxydeoxyguanosine (8 OHdG) levels, were also measured. ResultsThe average blood glucose reduction in diabetic rats with the Forskolin, Metformin, and Forskolin + Metformin treatments was 43.5%, 47.1%, and 53.9%, respectively. These reduction values for HCC rats after the treatments were 21.0%, 16.2%, and 23.7%, respectively. For all the diabetic and HCC rats treated with Forskolin/Metformin, the MDA, SOD, and GPx levels showed significant improvement compared with the diabetic and HCC groups (P < 0.05). Although the rats treated with Forskolin + Metformin experienced a higher reduction in oxidative stress of blood and urine samples compared to the Forskolin group, the differences between this group and rats treated with Metformin were not significant for all parameters. ConclusionMetformin and Forskolin reduced oxidative stress in diabetic and HCC-induced rats. The results indicated that the combination of agents (Metformin & Forskolin) had greater therapeutic effects than Forskolin alone in reducing glucose levels in diabetic rats. However, the ameliorative effects of combining Metformin and Forskolin on blood and urine oxidative stress were not statistically higher than those of Metformin alone.

Combination of retagliptin and henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, active-controlled, phase 3 trial.

This study assessed the efficacy and safety of co-administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. This multicentre, phase 3 trial consisted of a 24-week, randomized, double-blind, active-controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once-daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co-administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (-1.51%) and R100/H10 (-1.54%) groups compared with those receiving the corresponding doses of individual agents (-0.98% for R100, -0.86% for H5 and -0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2-h postprandial glucose were also more pronounced in the co-administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co-administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.

Abstract LB294: Targeting fatty acid oxidation to boost the anti-tumor effects of nutrient starvation in solid malignancies

Abstract Introduction Reducing glucose and growth factor provision to cancer cells through in vitro starvation (STV) or in vivo fasting/fasting-mimicking diets (FMDs) delays tumor progression and prolongs survival in tumor-bearing mice. More recently, cyclic FMD has been shown to be safe and associated with promising metabolic and immunomodulatory effects in cancer patients. However, cyclic fasting and FMD only retard tumor progression, but they do not result in tumor cure when used alone. Here, we hypothesized that tumor cells exposed to STV activate Fatty Acid Oxidation (FAO) as an alternative metabolic pathway that could be responsible for primary or acquired tumor cell resistance to STV. Methods We investigated the effects of FAO inhibition (FAOi) in combination with STV on the proliferation and survival of human or murine cell lines of Triple Negative Breast Cancer (TNBC) (n=16), HR+HER2- breast cancer (n=3), colorectal (n=1), pancreatic (n=1) and lung cancer (n=1), as well as of non-transformed human epithelial cells (n=3). STV consisted of a 50% reduction of extracellular glucose and serum in cell growth media. To inhibit FAO, we used the Carnitine Palmitoyl transferase 1 inhibitor Etomoxir or ST1326. Results STV+FAOi resulted in cooperative or highly synergistic antiproliferative effects in all cancer models tested, but not in normal cells. At longer time points, STV+FAOi enhanced tumor cell death through the activation of apoptosis. Depending on the specific tumor type, the cooperative effects of STV and FAOi were mostly mediated by glucose or fatty acid restriction in the STV medium. On the other hand, the reduction of extracellular growth factors did not affect cell proliferation upon STV+FAOi combination. Intracellular ATP levels were reduced upon cell exposure to the combined treatment at later time points. However, the supplementation of several sources of ATP, such as glutamine or TCA cycle intermediates, to tumor cells did not rescue the antitumor effects of STV+FAOi, thus excluding the strong impact of this combination on tumor cell bioenergetics. On the other hand, STV+FAOi caused an excessive intracellular antioxidant response, which in part mediated the synergistic effects of STV+FAOi. Indeed, Etomoxir alone mildly increased the NADPH/NADP+ ratio, whereas its combination with STV resulted in a remarkable increase of this ratio. In parallel, combining the antioxidant molecules n-acetylcysteine (NAC) and reduced glutathione (GSH) with FAOi caused antitumor effects that recapitulate those produced by STV+FAOi treatment. Conclusions FAO is a potential resistance mechanism to nutrient starvation, with broad antitumor activity in different models of murine and human malignancies, but not in normal cells. In cancer cells, FAOi synergizes with STV by strongly affecting intracellular redox balance. FAOi is a new strategy that should be explored in future preclinical in vivo experiments and in clinical studies to potentiate the antitumor effects of nutrient starvation in solid malignancies. Citation Format: Marzia Santamaria, Beatrice Cantarelli, Arta Ajazi, Chiara Milanese, Giulia Salvadori, Pier Giorgio Mastroberardino, Paola Antonia Corsetto, Giancarlo Pruneri, Filippo De Braud, Claudio Vernieri. Targeting fatty acid oxidation to boost the anti-tumor effects of nutrient starvation in solid malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB294.

“Hurdley technologies” utilized to improve postharvest life of asparagus spears (Asparagus officinalis L.)

Asparagus (Asparagus officinalis L.) has short shelf-life due to the high metabolic activity of the apical meristems. Storage at low temperature and high relative humidity is used commercially to keep fresh asparagus spears. Techniques denominated “Hurdley technologies” (UV-C or gamma irradiation) have been tested in fruits and vegetables to extend postharvest life. These technologies were used to extend postharvest shelf life of asparagus spears by inhibition of meristematic activity. Spears were irradiated with UV-C at dosages of 2.46, and 4.93 kJ m-2 and gamma irradiation at 1 and 1.5 kGy, before storage at 2°C and 90% relative humidity (RH) for 20 days. Metabolic heat (Rq) was measured in apical meristems, as well as whole spear respiration, sugars content, water potential components and color descriptors. Metabolic heat and whole spears respiration rate did not show differences due to effect of UV-C treatments, while spears treated with gamma radiation showed a metabolic activity inhibition of 10 and 15% for 1 and 1.5 kGy, respectively, while whole spear respiration rate was not affected. Changes in color variables showed a slight reduction in gloss. Sugars content in UV-C remained unchanged, while gamma radiation induced a reduction in glucose. An increase in fresh weight loss was noticeable on those treated with gamma irradiation. No changes in water potential components were observed. It was concluded the treatments used did not reported positive benefits in extending asparagus spears shelf life.

Effect of Combination of Porang and Moringa Flour on Blood Glucose Levels and Body Weight in Rats

Porang tuber is rich in fiber and low in calories of carbohydrates. Moringa oleifera leaf has a high protein and a low content of lipids. Obesity and diabetes mellitus are the risk factors of cardiovascular disease, also known as cardiovascular disease risk factors. Combining of porang and moringa as feed can increase nutrition without causing weight gain. This study aims to determine these two materials as antidiabetic and antiobesity agents. The samples are porang tuber, a combination of porang tuber and M. oleifera leaves, a combination of M. oleifera leaves and wheat flour, wheat flour, and standard feed of mice. The parameters tested in this study are analysis of macronutrients of feed, loss of weight of mice, average consuming feed in 28 days, and reduction of blood glucose with a glucometer. The results obtained are a combination of porang tuber and moringa had a low contain carbohydrates and a high contain lipids and protein, can reduction in body weight of 21%, the lowest consumption of feed, and the lowest fasting and postprandial blood glucose levels compared to the other feeds. A combination of porang and moringa can be an antidiabetic and antiobesity agent.

Evaluation of the Neuroprotective Action of &lt;i&gt;Azadirachta indica&lt;/i&gt; Leaves Extract in Streptozotocin-induced Diabetic Rodent Model

Among the most common and painful consequences of diabetes mellitus, Diabetic Peripheral Neuropathy (DPN) is one of the most common. For DPN management, a variety of techniques have been used, ranging from traditional medicines to alternative approaches. Natural compounds are also the focus of research to explore the possible treatment by replacing or combining with the existing therapies. Different neurological changes in diabetic neuropathy and the effect of the Azadirachta indica (neem) extract were assessed with nerve conduction velocity, and biochemical and histological analysis in Streptozotocin-induced diabetic mellitus. The therapeutic effect of the extract was evaluated with doses 100, 200 and 500mg/kg body weight for 4 weeks after induction of diabetes. The protective effect was evaluated by treating the animals with hydroalcoholic extract of neem leaves in 500mg/kg dose before the induction of diabetes and post-treatment with the standard drug Metformin (500mg/kg). Both resulted in a significant reduction in blood glucose, additionally, 500mg/kg body weight dose revealed the signs of neuroprotection in diabetic rats. Neem leaf extract appears to be promising for future investigations, which might contribute to the emergence of new drugs for diabetes treatment and diabetic neuropathy either alone or in combination with conventional therapies.

The effectiveness of pharmacological and lifestyle interventions to reduce the risk of diabetes and hyperglycaemia following gestational diabetes: A systematic review and meta-analysis.

To synthesize the available evidence to better understand the effectiveness of interventions to prevent or delay hyperglycaemia and Type 2 diabetes mellitus (T2DM) postnatally in women with current or previous gestational diabetes mellitus (GDM). We searched five databases up to December 2020 for primary peer-reviewed articles reporting postpartum glycaemic outcomes in women with (previous) GDM following pharmacological or lifestyle intervention. Outcomes were relative risk of T2DM or continuous measures of glycaemia, change or at follow-up. A minimum of two studies evaluating the same intervention-outcome combination were needed to conduct meta-analyses, otherwise studies were described narratively. Meta-regression was used to evaluate whether associations varied by additional variables. We assessed risk of bias using the Critical Appraisal Skills Programme checklist. PROSPERO record CRD42018102380. We included 31 studies in the review with a total sample size of 8624 participants, and 26 studies in meta-analyses. Two-thirds of studies followed up participants at 1 year or less. Pharmacological interventions were associated with reduced risk of T2DM (0.80 [95% CI 0.64-1.00], n = 6 studies), as were lifestyle interventions albeit with a smaller effect size (0.88 [95% CI 0.76-1.01], n = 12 studies). Dietary and physical activity interventions were associated with a small reduction in fasting plasma glucose, particularly in longer interventions, but inconsistent effects were seen for other continuous outcomes. Although possibly due to chance, interventions to reduce hyperglycaemia after GDM may be effective. Future research should improve understanding of how interventions affect glucose control and how to optimise interventions for this population.

Abstract 5685: MiR-345-5p attenuates pancreatic cancer metastasis through KLK7/E-Cad/β-Catenin/Rap1 axis

Abstract Background: Pancreatic cancer (PC) is a highly lethal malignancy with a 5-year survival rate of 10.8%, primarily attributed to early invasion and metastasis. Epithelial-to-mesenchymal transition (EMT) plays a crucial role in the metastatic progression of PC. Existing therapies, such as Gemcitabine, Abraxane, and FOLFIRINOX, have limited efficacy, emphasizing the need for identifying molecular targets to enhance PC patient survival. Recent advancements in miRNA therapies show promise, but a detailed understanding of miRNAs regulating PC growth and metastasis remains elusive. This study aims to uncover the role of miR-345-5p in regulating PC metastasis. Methods: A miRNA microarray analysis of KC mouse data identified miR-345-5P as one of the significantly down-regulated miRNA, targeting multiple metastasis-related genes. Expression of miR-345-5p in PC was assessed using published databases, validated through qPCR and ISH in PC cell lines, serum samples, and patient tissue. In vitro overexpression and in vivo assays elucidated the functional roles of miR-345-5p in PC metastasis. A computational approach and dual-luciferase assays were used to identify the target of miR-345-5p. Western blots, immunohistochemistry, and immunofluorescence were utilized to decipher miR-345-5p mediated molecular mechanisms. Results: MiR-345-5p expression was downregulated in PC tissue, serum, and cell lines compared to non-tumor tissues. Restoring miR-345-5p reduced PC cell proliferation, migration, and invasion in vitro and in vivo. KLK 7 was confirmed as a direct target, and functional experiments revealed miR-345-5p's acting as a tumor-suppressor by inhibiting the E-Cad/B-catenin/Rap1 axis signaling pathway. MiR-345-5p overexpression stabilized the E-Cadherin-β-catenin complex, leading to reduced β-catenin accumulation in the nucleus and thus leading to declined transcription of crucial genes (C-myc, cyclin D1 &amp; MMP7) responsible for PC progression. Given the pivotal role of the c-myc gene in metabolism, we performed a metabolomic analysis. The findings unveiled significant metabolic rewiring, marked by reductions in glucose and amino acid metabolism, attributable to decreased C-myc expression due to restoration of miR-345 in PC cells. Conclusion: MiR-345-5p overexpression negatively regulates PC proliferation and EMT by directly targeting KLK7/E-Cad/β-catenin/Rap1 axis. Restoring miR-345-5p with standard care therapies could be a promising strategy for improving survival in metastatic PC patients. Citation Format: Nagabhishek Sirpu Natesh, Susheel Kumar Nethi, Brianna M White, Jussuf T. Kaifi, Surinder K. Batra, Surya Mallapragada, Satyanarayana Rachagani. MiR-345-5p attenuates pancreatic cancer metastasis through KLK7/E-Cad/β-Catenin/Rap1 axis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5685.

Real-World Outcomes of Individualized Targeted Therapy with Insulin Glargine 300Units/mL in Insulin-Naïve Korean People with Type2 Diabetes: TOBE Study.

The TOujeo BEyond glucose control (TOBE) study evaluated clinical outcomes with insulin glargine 300units/mL (Gla-300) in insulin-naïve Korean people with type2 diabetes mellitus (T2DM) in a real-world setting. This 24-week, prospective, non-interventional, multicenter, open-label, single-arm, observational study included adults aged ≥ 20years with T2DM suboptimally controlled with oral hypoglycemic agents and/or glucagon-like peptide1 receptor agonists who require basal insulin. Eligible participants were assigned to either general target glycated hemoglobin (HbA1c < 7%) or individualized target groups as per physician's discretion considering guidelines and participants' characteristics. The primary endpoint was the proportion of participants achieving the HbA1c target (individualized or general) at 24weeks. Among 369 participants, 19.5% (72/369) of participants achieved the HbA1c target at week24; 37.5% (33/88) in the individualized and 13.9% (39/281) in the general target group. In both target groups, similar reductions in fasting plasma glucose and body weight were observed, with low incidence of hypoglycemia, and T2DM duration was significantly shorter in participants who did versus those who did not achieve the target HbA1c (individualized target group: 9.6 ± 8.0 versus 13.1 ± 8.4years, P = 0.0454; general target group: 10.2 ± 8.6 versus 12.8 ± 7.4years, P = 0.0378). This study showed that initiation of insulin therapy with Gla-300 in people with T2DM using an individualized approach is more effective in achieving an HbA1c target. Moreover, earlier initiation of insulin therapy in people with suboptimally controlled T2DM may increase the success rate of glycemic control. A graphical abstract is available with this article.

Abstract P141: T2D-DNA Methylation Score and Changes in Glycemic Traits in Response to Weight-Loss Dietary Interventions: The MACRO Trial

Introduction: Epigenome-wide association studies (EWAS) have identified several CpGs associated with type 2 diabetes (T2D). A previous study has shown that a DNA methylation score provided more comprehensive information related to T2D risk than individual CpGs. However, whether such T2D-DNA methylation score is associated with changes in glycemic traits in response to weight loss dietary interventions remains unknown. Hypothesis: We hypothesized that a T2D-related DNA methylation score was associated with changes in glycemic traits in response to weight-loss dietary interventions; and may modify the effect of the interventions. Method: The current study included 147 participants from the MACRO trial, who were randomly assigned to a low-fat diet or a low-carbohydrate diet. A weighted DNA methylation score was created by 5 CpGs (cg19693031 at TXNIP , cg11024682 at SREBF1 , cg02650017 at PHOSPHO1 , cg18181703 and SOCS3 , and cg06500161 at ABCG1 ) from a previous EWAS at baseline. One-year changes in glycemic traits were calculated. Results: We found that a higher DNA methylation score was significantly associated with greater reductions in glucose (β: -3.20, SE: 1.08, p=0.003), insulin (β: -2.29, SE: 0.86, p=0.009), and homeostasis model assessments of insulin resistance (HOMA-IR, β: -0.86, SE: 0.30, p=0.005). The DNA methylation score was more strongly associated with changes in glycemic traits than any individual CpG sites ( Figure ). In addition, DNA methylation score significantly interacted with dietary interventions (low-fat vs. low-carbohydrate). The beneficial associations appeared to be stronger among participants with the low-carbohydrate diet (p-interaction=0.009 for glucose, 0.003 for insulin, and 0.004 for HOMA-IR). Conclusions: Our data indicate that a higher DNA methylation score was significantly associated with greater reductions in glycemic traits in response to weight-loss dietary interventions; such beneficial associations were stronger among those who consumed a low-carbohydrate diet.

Genetic Evidence of Causal Relation Between Intestinal Glucose Absorption and Early Postprandial Glucose Response: A Mendelian Randomization Study.

The post-prandial glucose response is an independent risk factor for type 2 diabetes. Observationally, early glucose response after an oral glucose challenge has been linked to intestinal glucose absorption, largely influenced by the expression of sodium-glucose-co-transporter-1 (SGLT1). This study utilizes Mendelian randomization (MR) to estimate the causal effect of intestinal SGLT1 expression on early glucose response. Involving 1547 subjects with class II/III obesity from the ABOS cohort, the study employs SGLT1 genotyping, oral glucose tolerance tests, and jejunal biopsies to measure SGLT1 expression. A loss-of-function SGLT1 haplotype served as the instrumental variable, with intestinal SGLT1 expression as the exposure and the change in 30-minute post-load glycemia from fasting glycemia (Δ30 glucose) as the outcome. Results showed that 12.8% of the 1,342 genotyped patients carried the SGLT1 loss-of-function haplotype, associated with a mean Δ30 glucose reduction of -0.41 mmol/L and a significant decrease in intestinal SGLT1 expression. The observational study linked a one standard deviation decrease in SGLT1 expression to a Δ30 glucose reduction of -0.097 mM/L. MR analysis paralleled these findings, associating a statistically significant reduction in genetically instrumented intestinal SGLT1 expression with a Δ30 glucose decreases of -0.353. In conclusion, the MR analysis provides genetic evidence that reducing intestinal SGLT1 expression causally lowers early post-load glucose response. This finding has a potential translational impact on managing early glucose response in type 2 diabetes.

Screening and Optimization of α-Glucosidase Inhibitor Production by Potent Strain of Bacillus subtilis Isolated from Peruyaan, Fermented Soy-Food of Northeast India

Background. Fermented soy foods exhibit the capability to inhibit the α-glucosidase enzyme. The bacteria isolated from these fermented soy foods may contribute to the production of a higher quantity of α-glucosidase inhibitor (α-GI) in optimized condition. Aim. The present study aims to isolate α-glucosidase inhibitor producing bacterial strain from peruyaan, a traditional fermented soy food of Arunachal Pradesh, optimize the production of α-GI for maximum yield, and assess the compounds. Result. Bacillus subtilis PM NEIST_4 (identified by 16S rRNA gene sequencing) was isolated as a potential strain that exhibit maximum α-glucosidase inhibition. This strain showed maximum α-GI productivity in Mueller Hinton Broth (MHB). The cultivation parameters for fermentation of MHB were optimized in order to maximize the yield of α-GIs. The α-GI productivity of 1616.613 ± 84.54 U/mL was observed before optimization, which increased by almost three times after optimization (4808.324 ± 13 U/mL). In vitro assays against α-glucosidase enzyme revealed a significant IC50 value of 596.532 ± 44.80 μg/mL after the optimized study compared to that before optimization (IC50 1705.617 ± 43.95 ug/mL). Besides, α-glucosidase enzyme inhibitory property of fermented MHB (FMHB) was found to be unaffected at varied range of pH and temperature. Oral gavaging of FMHB in sucrose-loaded Wistar rat exhibited maximum reduction in postprandial blood glucose at 400 mg/kg body weight. Furthermore, FMHB was fractionated using solvents of increasing polarity including n-hexane, ethyl acetate, and n-butanol. Ethyl acetate fraction that exhibited the strongest inhibitory action against the α-glucosidase enzyme (IC50 value of 251.55 ± 19.65 μg/mL), showed the presence of pyrrolopyrazine derivatives through GC-MS and LC-MS analyses. Conclusion. The present study demonstrated the isolation of a potent α-GI producing bacterial strain from traditional fermented soy food, and the optimization of the bacterial fermentation process was achieved to maximize the yield of α-GI. These findings underscore promising industrial potential of B. subtilis PM NEIST_4, advocating the use of indigenous microbial resources for the production of α-GI.