Reduced Glucose Concentrations Research Articles

Nutritional Potency of Mangifera indica L. (Mango): Focus on Mango as Antioxidant

Background: Mango, known as "the king of fruits," is one of the most popular fruits on the planet. Vitamins, minerals, antioxidants, and bioactive substances abound. Objective: In the present review, we aimed to explore the therapeutic effects of mango as an antioxidant. Methods: Scopus and ScienceDirect databases were used to gather research papers over the pre-vious 12 years. Results: Our research explores the formidable antioxidant potential of mango, driven by its ele-vated phenolic and flavonoid content. Within mango, crucial metabolites such as glutathione and euxanthone contribute significantly to its antioxidant and anti-inflammatory prowess. A note-worthy bioactive compound, Mangiferin, found in mango, exhibits anti-diabetic properties by inhibiting sucrase and isomaltase, consequently reducing glucose absorption in the intestine. Conclusion: In our study, mango has demonstrated its ability to lower blood sugar levels, en-hance insulin production, and reduce lipid levels. These beneficial effects are attributed to high soluble fiber, polyphenols, and carotenoids, including quercetin and beta-carotene. Our findings shed light on the multifaceted health-promoting attributes of mango, positioning it as a valuable natural resource for potential dietary interventions and health enhancement. In conclusion, ef-fective blood sugar management hinges on strategic dietary decisions. Steering clear of high-glycemic combinations with mangoes, choosing daytime consumption, and integrating regular physical activity for energy equilibrium is paramount.

Dose-Response Relationship of Phloretin Therapy on Water and Glucose Transport during Experimental Peritoneal Dialysis.

Water retention, ultrafiltration insufficiency, and metabolic complications due to abnormally high glucose concentrations are still common problems in patients treated with peritoneal dialysis. Phloretin, a nonselective inhibitor of facilitative glucose transporter channels (GLUT), has shown to improve water transport and lower glucose absorption in experimental peritoneal dialysis. However, the dose-response relationship remains unknown, and we therefore performed a dose-response study to elucidate the pharmacodynamic properties of intra-peritoneal phloretin therapy. Experimental peritoneal dialysis was performed in fifty healthy Sprague-Dawley rats, using glucose-based dialysis fluid containing five different concentrations of phloretin. We utilized radiolabeled 18F-deoxyglucose (18-FDG) to determine the plasma-to-dialysate transport. The data was then analyzed to determine the dose-response relationship of phloretin according to the Hill-model equation. Intraperitoneal phloretin therapy followed a dose-response relationship where higher concentrations of phloretin lowered the diffusion capacity of 18-FDG and conventional glucose, while enhancing ultrafiltration. Phloretin showed high potency for water removal and diffusion outcomes, requiring low concentrations to achieve substantial effects. Intraperitoneal phloretin therapy followed a distinct dose-response relationship, showing high potency in improving ultrafiltration and reducing glucose absorption in experimental PD. These findings support the therapeutic potential of GLUT-inhibitors like phloretin and support future clinical studies to evaluate efficacy and optimal dosing in patients undergoing PD.

Multitasking Asynchronous Collaborative Nanosystem for Diabetic Wound Healing Based on Hypoglycemic, Antimicrobial, and Angiogenesis-Promoting Effects.

A diabetic foot ulcer(DFU) is a common and serious complication of diabetes. This complication can result in amputation and death because of the several challenges associated with wound healing that can be attributed to the complex wound microenvironment, including biofilm infection, hyperglycemia, and diabetic angiopathy. Existing investigations on the wound-healing rate consider only one or two pathogenic factors, and therefore, despite the extensive research on these pathological microenvironments, there is an urgent need to optimize the wound-healing rate in patients with diabetic foot ulcers. To this end, a multitasking asynchronous collaborative nanosystem is designed in this study. The designed nanosystem can efficiently clear biofilm infections using optimized photodynamic therapy based on a poly photosensitizer ionic liquid (i.e., Ce6IL), reduce local blood glucose concentration using glucose oxidase, and reconstruct blood vessels by stimulating endothelial cell proliferation and migration using nitric oxide. The experimental results indicate that the three-step sequential collaboration strategy for clearing biofilm infections, reducing glucose concentrations, and reconstructing damaged blood vessels can help significantly accelerate wound healing rate in patients with diabetic foot ulcers.

ASSESSMENT OF BLOOD GLUCOSE LEVELS IN WISTAR RATS TREATED WITH COCCINIA GRANDIS AND DATA INTERPRETATION BASED ON NON-COMPARTMENT ANALYSIS AND RATE PROCESS

The study aims to examine the blood glucose-lowering effects of fresh Coccinia grandis fruit and assess how drying affects its antidiabetic potential. Additionally, the study seeks to determine the optimal administration procedure to maximize its antidiabetic efficacy. An oral glucose tolerance test was performed in female Albino Wistar rats to study the effects of C. grandis in three forms: fresh fruit slurry, dry fruit powder, and overnight soaked dry powder, with metformin as standard. The fresh fruit slurry (S-1) of C. grandis demonstrates excellent antidiabetic properties, showing a mean blood glucose level of 116.25±38 and a percentage blood glucose reduction of about 30%. This is more effective compared to the processed form of C. grandis and the standard drug metformin, with a mean actual blood glucose level of 44.5±35.9. The study indicates that C. grandis fresh form possesses significant hypoglycemic effects, reducing glucose absorption by peripheral tissues and enhancing glucose uptake into cells.

Quercetin: Potential antidiabetic effects through enzyme inhibition and starch digestibility

AbstractDiabetes mellitus involves high blood sugar levels due to insufficient insulin action. Furthermore, enzymes such as α‐amylase and α‐glucosidase break down carbohydrates into glucose, leading to postprandial hyperglycemia. Flavonoids, particularly quercetin, inhibit these enzymes, slowing carbohydrate digestion and reducing glucose absorption. Quercetin has significant hypoglycemic effects with inhibitory concentration (IC50) values comparable to acarbose, a standard inhibitor, suggesting its potential as a natural alternative for diabetes management. In silico models, including molecular docking, molecular dynamics (MD) simulations, and quantitative structure‐activity relationship (QSAR) approaches, help researchers understand the molecular interactions of therapeutic agents. These techniques identify potential inhibitors, determine enzyme‐inhibitor structures, and calculate binding energies, correlating findings with in vitro or in vivo data. Molecular docking predicts molecular orientations, MD simulations offer insights into enzyme–inhibitor dynamics, and QSAR models predict inhibitory potential based on structural properties. Studies have shown that quercetin effectively inhibits α‐glucosidase and α‐amylase by forming hydrogen bonds with specific amino acid residues. Quercetin interacts with starches and reduces their digestibility, increases the formation of resistant starch, lowers the glycemic index, and inhibits digestive enzymes. Studies show that the effects of quercetin on starch digestion vary with concentration and type of starch, and its incorporation into foods such as bakery products, pasta, etc. can significantly decrease starch hydrolysis. The incorporation of quercetin into starch matrices may aid in the development of functional foods aimed at improving glycemic control.

Antidiabetic Potential of Nypa fruticans Fronds: Inhibition of α-Amylase, α-Glucosidase, and Glucose Absorption In Vivo

Background: Diabetes mellitus (DM) results from insulin resistance or impaired insulin secretion, leading to hyperglycemia, which, in advanced stages, causes macrovascular and microvascular complications. Effective management of postprandial hyperglycemia is critical to reducing these complications. Inhibition of carbohydrate hydrolyzing enzymes such as α-amylase and α-glucosidase offers a therapeutic approach for controlling postprandial glucose levels. While acarbose is a known inhibitor of these enzymes, its long-term use can cause gastrointestinal side effects. Therefore, alternative treatments, such as medicinal plants, are being explored. This study focuses on the antidiabetic potential of the Nipah frond (Nypa fruticans Wurmb), a traditional remedy, which is believed to inhibit glucose absorption and carbohydrate degradation. Methods; Nipah frond powder was extracted using ethanol through maceration. Phytochemical screening was conducted to detect bioactive compounds, and in vivo and in vitro assays were performed to evaluate antidiabetic properties. The inverted intestinal pouch technique assessed glucose absorption, while the Oral Glucose Tolerance Test (OGTT) was conducted on male Wistar rats. Enzyme inhibition assays for α-amylase and α-glucosidase were carried out to measure the extract's effectiveness in inhibiting carbohydrate degradation. Results: In vitro tests demonstrated that the ethanol extract exhibited inhibitory activity against both α-amylase and α-glucosidase enzymes, with IC50 values of 38.493 ± 0.900 ppm and 40.401 ± 0.558 ppm, respectively. In vivo studies using the everted sac technique showed that the extract reduced glucose absorption by 74.10% compared to the control group, similar to acarbose. In the OGTT, administration of 1000 mg/kg BW of Nipah frond extract significantly reduced postprandial glucose levels, with an area under the curve (AUC) comparable to glibenclamide. Conclusion: The ethanol extract of Nypa fruticans fronds demonstrated significant antidiabetic activity by inhibiting α-amylase and α-glucosidase, reducing glucose absorption, and suppressing postprandial hyperglycemia in vivo.

Diabetes Management: Herbal Remedies and Emerging Therapies

Abstract: Diabetes is a chronic disease affecting millions worldwide, characterized by inadequate insulin production or malfunctioning insulin action, leading to elevated blood sugar levels. Its prevalence is escalating globally, with estimates projecting a rise from 2.8% to over 5.4% of the world's population by 2025. In India, diabetes poses a significant health challenge, especially in urban areas. While conventional medications are widely available, herbal remedies have gained popularity due to their potential for fewer side effects and lower costs. Herbal remedies have been employed for centuries in diabetes management and have been extensively studied for their blood sugar regulatory properties. Prominent herbs studied for their potential to manage diabetes include gymnema, cinnamon, fenugreek, and bitter melon. These herbs are believed to enhance insulin sensitivity, reduce glucose absorption in the intestines, and improve glucose metabolism. This review highlights emerging alternative treatment options, such as stem cell therapy and gene therapy, in the field of diabetes management. Stem cell therapy aims to regenerate insulin-producing cells or enhance their function, while gene therapy targets the underlying genetic factors contributing to diabetes. These innovative approaches hold promise for more effective and personalized treatments in the future. It is essential to emphasize that any diabetes treatment or remedy should be discussed with a healthcare professional. Diabetes management requires a personalized approach based on individual needs and medical history. The integration of herbal remedies and alternative treatment options into conventional diabetes management warrants further research to determine their efficacy, safety, and potential for widespread implementation

Incorporation of microencapsulated polyphenols from jabuticaba peel (Plinia spp.) into a dairy drink: stability, in vitro bioaccessibility, and glycemic response

This work incorporated bioactives extracted from jabuticaba peel in the form of concentrated extract (JBE) and microencapsulated powders with maltodextrin (MDP) and gum arabic (GAP) in a dairy drink, evaluating its stability, in vitro bioaccessibility, and glycemic response. We evaluated the pH, acidity, colorimetry, total phenolics and anthocyanins, antioxidant capacity, degradation kinetics and half-life of anthocyanins, bioaccessibility, and postprandial glycemic physicochemical characteristics response in healthy individuals. The drinks incorporated with polyphenols (JBE, GAP, and MDP) and the control dairy drink (CDD) maintained stable pH and acidity over 28 days. In color, the parameter a*, the most relevant to the study, was reduced for all formulations due to degradation of anthocyanins. Phenolic and antioxidant content remained constant. In bioaccessibility, we found that after the gastrointestinal simulation, there was a decrease in phenolics and anthocyanins in all formulations. In the glycemic response, we observed that the smallest incremental areas of glucose were obtained for GAP and JBE compared to CDD, demonstrating that polyphenols reduced glucose absorption. Then, the bioactives from jabuticaba peel, incorporated into a dairy drink, showed good storage stability and improved the product’s functional aspects.

Soybean molasses increases subcutaneous fat deposition while reducing lipid oxidation in the meat of castrated lambs.

This study aimed to evaluate the effect of including soybean molasses (SM) on performance, blood parameters, carcass traits, meat quality, fatty acid and muscle (longissimus thoracis) transcriptomic profiles of castrated lambs. Twenty Dorper × Santa Inês lambs (20.06 ± 0.76kg BW) were assigned to a randomized block design, stratified by BW, with the following treatments: CON - 0g/kg of SM and SM20 - 200g/kg of SM on DM basis, allocated in individual pens. The diet consisted of 840g/kg concentrate and 160g/kg corn silage for 76 days, with the first 12 days as an adaptation period and the remaining 64 days on the finishing diet. The SM20 diet increased blood urea concentration (P = 0.03) while reduced glucose concentration (P = 0.04). Lambs fed SM showed higher subcutaneous fat deposition (P = 0.04) and higher subcutaneous adipocyte diameter (P < 0.01), in addition to reduced meat lipid oxidation (P < 0.01). Soybean molasses reduced the quantity of branched-chain fatty acids in longissimus thoracis (P = 0.05) and increased the quantity of saturated fatty acids (P = 0.01). In the transcriptomic analysis, 294 genes were identified as differentially expressed, which belong to pathways such as oxidative phosphorylation, citric acid cycle, and monosaccharide metabolic process. In conclusion, diet with SM increased carcass fat deposition, reduced lipid oxidation, and changed the energy metabolism, supporting its use in ruminant nutrition.

Effect of intermittent hypoxia on glucose tolerance in adults with type 2 diabetes

Hypoxia stimulates glucose uptake through an insulin-independent pathway. The purpose of this single-blind randomized study was to determine the acute effect of intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, on glucose and insulin concentrations during an oral glucose tolerance test in adults with type 2 diabetes. It was hypothesized that intermittent hypoxia would attenuate the increase in glucose and insulin concentrations during an oral glucose tolerance test. Six adults with type 2 diabetes (5 men, age: 51±15 years, HbA1c: 7.3±1.5%) visited the laboratory on two occasions. On both visits, a 2-hour oral glucose tolerance test was performed, with venous blood samples collected 0, 30, 60, 90, and 120 min after ingestion of a high-glucose drink. Following ingestion of the drink, participants were exposed to either an intermittent hypoxia (IH) protocol, consisting of eight 4-min hypoxic cycles at a targeted arterial oxygen saturation of 80% interspersed with breathing room air to resaturation, or an intermittent normoxia (IN) protocol consisting of eight 4-min normoxic cycles interspersed with breathing room air. By design, oxygen saturation was lower during intermittent hypoxia than intermittent normoxia (81±3 vs. 97±1%, p&lt;0.01). Relative changes in plasma glucose concentrations in response to the oral glucose tolerance tests were not different between conditions (IH vs. IN: 30: 42±15 vs. 35±15; 60: 57±26 vs. 65±30; 90: 73±32 vs. 88±30; and 120: 78±26 vs. 83±29 mg/dl, interaction effect: p=0.13). Similarly, the relative changes in insulin concentrations in response to the oral glucose tolerance tests were not different between conditions (IH vs. IN: 30: 14±17 vs. 25±17; 60: 42±36 vs. 48±35; 90: 70±58 vs. 86±60; and 120: 103±72 vs. 125±94 ulU/ml, main effect for condition: p=0.12). While these preliminary results did not reach statistical significance, the observed trends for reduced glucose concentrations in combination with lower insulin concentrations during intermittent hypoxia suggest that short bouts of hypoxia improve glucose tolerance by stimulating glucose uptake independently from the action of insulin. Data from a larger sample size of adults with type 2 diabetes are needed to confirm these preliminary findings. None. 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.

Functional assessments of Psidium guajava L. and Morus alba L. leaf extracts on postprandial glucose control.

Diabetes is a leading cause of death, according to statistics published by the Department of Health, Executive Yuan of Taiwan. In modern medicine, diabetes can be controlled using various medications; however, some drugs often have undesirable side effects. It therefore became a goal to find plant-based material that can reduce glucose concentration in the blood while reducing the incidence of complications and not causing side effects. Alpha-glucosidase inhibitors (AGIs) are effective glucose-lowering medicines and are enzymes essential to carbohydrate digestion. Inhibition of α-glucosidase leads to a delayed and reduced rise in postprandial blood glucose levels. This study evaluates the inhibitory effect of mixed extracts of Psidium guajava L. and Morus alba L. leaves on α-glucosidase activity and postprandial hyperglycemia in normal and diabetic rats. The inhibition of α-glucosidase activity was assayed invitro. Half maximal inhibitory concentration (IC50) values of Psidium guajava L. and Morus alba L. were 2.25 and 0.1 mg/mL, respectively. The IC50 value of a commercial anti-hyperglycemic agent (Glucobay) is 6.41 mg/mL. The IC50 value of a mixture of extracts of Psidium guajava L. and Morus alba L. was 0.07 mg/mL. In cytotoxicity tests, survival percentages and shape did not significantly affect the murine embryonic liver cell line (BNL CL.2) when treated with varying concentrations of mixture extracts for varying periods of time. In summary, Psidium guajava L. and Morus alba L. showed positive anti-diabetes activity and suggested promising potential for alternative functional foods for diabetes mellitus (DM) patients.

Study on Antidiabetic Potential of Sessuvium Portulacastrum Aqueous Extract: An In-Silico and In-Vitro Analysis.

Diabetes mellitus is a persistent metabolic condition marked by elevated blood glucose levels due to compromised insulin secretion or functionality. The search for natural antidiabetic agents has gained attention due to their potential effectiveness and safety profiles. Sessuvium portulacastrum, a coastal plant, has been traditionally used for various medicinal purposes. This study investigates the antidiabetic potential of Sessuvium portulacastrum aqueous extract by analyzing its inhibitory effects on key enzymes involved in carbohydrate metabolism and exploring its molecular interactions with critical target proteins. The aqueous extract of Sessuvium portulacastrum was prepared and used for in vitro analysis. The reduced activity of the extract against α-amylase and α-glucosidase enzymes, crucial in glucose absorption and postprandial hyperglycemia, was assessed. Molecular docking techniques were employed to explore the potential interactions between active compounds in the extract and diabetes-related proteins, including BAX, GSK3β, and CADH. The study revealed significant inhibition of both alpha-amylase and alpha-glucosidase enzymes by Sessuvium portulacastrum aqueous extract, indicating its potential to reduce glucose absorption and postprandial hyperglycemia. Moreover, the molecular docking analysis demonstrated strong binding interactions between active compounds in the extract and key proteins involved in diabetes-related pathways, namely apoptotic pathways, glycogen synthesis, and cell adhesion. The findings of this study highlight the promising antidiabetic potential of Sessuvium portulacastrum aqueous extract. Upcoming research should get an attention on isolating and characterizing the active compounds responsible for these effects on antidiabetic therapies from natural sources.

Corchorus olitorius Aqueous Lyophilized Leaves Scavenge Radicals and Inhibit Diabetes-related Enzymes Uncompetitive

Corchorus olitorius L. is extensively consumed in Nigeria and is believed to reduce glucose absorption from glucose-rich complementary meals. This study investigated the radical scavenging and diabetes-related enzyme inhibitory properties of C. olitorius aqueous lyophilized leaves (CO). Quantitative phytochemical analysis, radical scavenging assessments, reducing power, antioxidant capacity, and carbohydrate metabolizing enzyme inhibitory activity were all determined using standard biochemical methods. Phytochemical analysis revealed the presence of flavonoids (513.95 ± 36.88 mg RE/g), tannins (345.64 ± 12.66 mg TAE/g), phenols (10.24 ± 0.23 mg GAE/g), β-carotene (1.12 ± 0.28 mg CE/g) and lycopene (0.58 ± 0.10 mg CE/g). CO scavenged 2, 2-diphenyl-2-picrylhydrazyl radical, exhibited reducing power and antioxidant capacity at the highest concentration compared to the reference standards. α-amylase and α-glucosidase enzyme inhibitory activities were also observed; however, they were lower (p&lt;0.05) than acarbose. Both α-amylase and α-glucosidase were inhibited uncompetitively by CO, reducing their Vmax and Km. Conclusively, C. olitorius can be utilized in managing postprandial hyperglycemia when consumed with glucose-rich complementary meals.

Investigating the role of an immediate early gene FOS as a potential regulator of autophagic response to hypoglycemia in embryonic hypothalamic neurons.

Hypoglycemia-associated autonomic failure (HAAF) is a well-established complication of diabetes. Although HAAF has serious outcomes such as recurrent morbidity, coma, and death, the mechanisms of HAAF and its pathological components are largely unknown. Our previous studies have revealed that hypoglycemia is associated with the upregulation of an immediate early gene - FOS. In addition, it is documented that glucose deprivation activates neuronal autophagic activities. Therefore, the present study aimed to identify the role of FOS and one of the core components of the autophagy pathway, Beclin-1 (encoded by the BECN1 gene), in the regulation of autophagic mechanisms in embryonic hypothalamic neurons in response to hypoglycemic conditions. Embryonic Mouse Hypothalamic Cell Line N39 (mHypoE-N39 or N39) was cultured in reduced concentrations of glucose (2000, 900, 500, and 200 mg/L). Gene and protein expression, as well as immunofluorescence studies on autophagy were conducted under different reduced glucose concentrations in N39 hypothalamic neurons with and without FOS and BECN1 gene knockdowns (KD). The outcomes of the present study have demonstrated a significant increase in autophagosome formation and subsequent lysosomal degradation in the hypothalamic neurons in response to reduced glucose concentrations. This hypoglycemic response appears to be lowered to a similar extent in the FOS KD and BECN1 KD cells, albeit insignificantly from the negative control, is indicative of the involvement of FOS in the autophagic response of hypothalamic neurons to hypoglycemia. Moreover, the KD cells exhibited a change in morphology and reduced cell viability compared with the control cells. Our findings suggest that reduced FOS expression could potentially be associated with impaired autophagic activities that are dependent on BECN1, which could lead to decreased or blunted hypothalamic activation in response to hypoglycemia, and this, in turn, may contribute to the development of HAAF.

Effect of preoperative oral carbohydrates on insulin resistance in patients undergoing laparoscopic cholecystectomy: a randomized controlled trial

PurposeThe present research seeks to clarify the consequences of two specific preoperative oral carbohydrate (POC) amounts on insulin resistance (IR) and stomach evacuation in laparoscopic cholecystectomy (LC) patients.MethodsA total of 129 patients set for elective LC procedures were randomly assigned to a control group (C, n = 45), a 200 mL POC group (P1, n = 42), and a 400 mL POC group (P2, n = 42). The C group was fasted from midnight until surgery, whereas the P1 and P2 groups received their respective carbohydrate volumes 2–4 h before anesthesia. Fasting blood glucose, insulin, and glucagon concentrations were measured at three junctures. IR metrics were derived by employing the homeostasis model assessment. Gastric volume was measured before anesthesia using gastric ultrasound. Inter-group comparisons included IR indicators, subjective comfort scores, and hemodynamic data.ResultsAt T2, the C group exhibited reduced glucose concentrations compared to the P2 group (4.73 ± 0.64 vs. 5.26 ± 1.02 mmol/L, p < 0.05). The Perlas grading indicated that grade 1 was more prevalent in the P2 group than in the P1 and C groups (18 [42.9%] vs. 6 [14.3%] and 1 [2.2%], p < 0.05). Additionally, thirst and hunger metrics for the P2 group were notably reduced compared to the C group at both T2 and T3.ConclusionAdministering either 200 mL or 400 mL of carbohydrates 2–4 h pre-surgery had no detectable impact on IR or gastric volume in LC patients.Trial registrationChiCTR, ChiCTR2200065648. Registered January 13, 2023, http://www.chictr.org.cn.

Evaluation of Anti-Diabetic Activity of Zinc Oxide Nanoparticles of Gymnema sylvestre Extract on Wistar Rats

Diabetes mellitus is described as a metabolic disorder, which was characterised by high blood glucose levels, which were resulted due to insufficient insulin secretion. There were major complications related to diabetes mellitus. To evaluate the antidiabetic effect of Gymnema sylvestre Zinc Oxide Nanoparticles. Streptozotocin (STZ) of 50mg/kg is used for the induction of diabetes into Wistar rats. The animals were divided into 6 groups. Group-I represented as Control; Group-II represented as diabetic control (STZ ); Group-III represented as 5 mg/kg body weight of glibenclamide + diabetes; Group-IV represented as Gymnema sylvestre extract + diabetes; Group-V represented as 100 µg Gymnema sylvestre Zinc Oxide nanoparticles + diabetes; group-6- Gymnema sylvestre Zinc Oxide Nanoparticles 200 µg + diabetes. The GsZnONPs were inspected to morphological properties using UV spectrophotometer and FTIR. The GsZnONPs shown characterization peak at 300nm. The study has shown that GsZnONPs treated group has shown reduced glucose concentration. The histo-pathological alterations were also studied in all experimental groups. The pathology results of GsZnONPs (200 µg) group has shown the regeneration of islets cells of pancreas. The research study has proved that Gymnema sylvestre ZnO NPs exerts antidiabetic properties.&#x0D; Keywords: Diabetes, Gymnema sylvestre, Zinc Oxide nanoparticles

Reduced glucose concentration enhances ultradian rhythms in Pdcd5 promoter activity in vitro.

Intrinsically driven ultradian rhythms in the hourly range are often co-expressed with circadian rhythms in various physiological processes including metabolic processes such as feeding behaviour, gene expression and cellular metabolism. Several behavioural observations show that reduced energy intake or increased energy expenditure leads to a re-balancing of ultradian and circadian timing, favouring ultradian feeding and activity patterns when energy availability is limited. This suggests a close link between ultradian rhythmicity and metabolic homeostasis, but we currently lack models to test this hypothesis at a cellular level. We therefore transduced 3T3-L1 pre-adipocyte cells with a reporter construct that drives a destabilised luciferase via the Pdcd5 promotor, a gene we previously showed to exhibit robust ultradian rhythms in vitro. Ultradian rhythmicity in Pdcd5 promotor driven bioluminescence was observed in >80% of all cultures that were synchronised with dexamethasone, whereas significantly lower numbers exhibited ultradian rhythmicity in non-synchronised cultures (∼11%). Cosine fits to ultradian bioluminescence rhythms in cells cultured and measured in low glucose concentrations (2mM and 5mM), exhibited significantly higher amplitudes than all other cultures, and a shorter period (6.9h vs. 8.2h, N = 12). Our findings show substantial ultradian rhythmicity in Pdcd5 promotor activity in cells in which the circadian clocks have been synchronised in vitro, which is in line with observations of circadian synchronisation of behavioural ultradian rhythms. Critically, we show that the amplitude of ultradian rhythms is enhanced in low glucose conditions, suggesting that low energy availability enhances ultradian rhythmicity at the cellular level in vitro.

WITHDRAWN: Estrogen regulates duodenal glucose absorption by affecting estrogen receptor-α on glucose transporters

The mechanisms of estrogen in glucose metabolism are well established; however, its role in glucose absorption remains unclear. In this study, we investigated the effects of estrogen on glucose absorption in humans, mice, and SCBN intestinal epithelial cells. We first observed a correlation between estrogen and blood glucose in young women and found that glucose tolerance was significantly less in the premenstrual phase than in the preovulatory phase. Similarly, with decreased serum estradiol levels in ovariectomized mice, estrogen receptors alpha (ERα) and beta (ERβ) in the duodenum were reduced, and weight and abdominal fat increased significantly. The expression of sodium/glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2) and glucose absorption in the duodenum decreased significantly. Estrogen significantly upregulated SGLT1 and GLUT2 expression in SCBN cells. Silencing of ERα, but not ERβ, reversed this trend, suggesting that ERα may be key to estrogen-regulating glucose transporters. A mechanistic study revealed that downstream, estrogen regulates the protein kinase C (PKC) pathway. Overall, our findings indicate that estrogen promotes glucose absorption, and estrogen and ERα deficiency can inhibit SGLT1 and GLUT2 expression through the PKC signaling pathway, thereby reducing glucose absorption.

Knockdown of TMEM30A in renal tubular epithelial cells leads to reduced glucose absorption

The kidney reabsorbs large amounts of glucose through Na+-glucose cotransporter 2 (SGLT2). P4-ATPase acts together with the β-subunit TMEM30A to mediate the asymmetric distribution of phosphatidylserine (PS), phosphatidylethanolamine (PE), and other amino phospholipids, promoting plasma membrane and internal vesicle fusion, and facilitating vesicle protein transport. We observed reduced TMEM30A expression in renal tubules of DKD and IgA patients, suggesting a potential role of TMEM30A in renal tubular cells. To investigate the role of TMEM30A in renal tubules, we constructed a TMEM30A knockdown cell model by transfecting mouse kidney tubular epithelium cells (TCMK-1) with TMEM30A shRNA. Knockdown of TMEM30A in TCMK-1 cells attenuated vesicle transporter protein synthesis, resulting in reduced transport and expression of SGLT2, which in turn reduced glucose absorption. These data suggested that TMEM30A plays a crucial role in renal tubules.

1575-P: Glycerol Metabolism and Gluconeogenesis in Mice Lacking the Mitochondrial Pyruvate Carrier in Hepatocytes

Hepatic glucose production from glycogen breakdown and gluconeogenic substrates is an important physiologic adaptation, but uncontrolled glucose release by the liver contributes to hyperglycemia in diabetes. The liver can produce glucose from several substrates, including amino acids, lactate/pyruvate, and glycerol. Mitochondrial import of pyruvate by the mitochondrial pyruvate carrier (MPC) plays an important role in gluconeogenesis from lactate/pyruvate, but its role in gluconeogenesis from other substrates is less clear. For example, glycerol can be converted to glucose by two pathways; [1] a direct pathway involving the reversal of several steps in glycolysis and [2] a mitochondrial pathway requiring the import of pyruvate via the MPC. While prior work has shown that compared to wild-type (WT) mice, hepatocyte MPC-/- mice exhibit lower blood glucose concentrations after fasting 24 h, concentrations after fasting 18 h were not different between genotypes in the present study. To determine whether gluconeogenesis from glycerol was affected by MPC deficiency, we administered 13C-glycerol to overnight fasted WT and MPC knockout mice and found that loss of the MPC increased the incorporation of 13C into new glucose. Further analysis determined that MPC deletion reduced the incorporation of 13C into glucose derived from the mitochondrial pathway and hepatic TCA cycle metabolites, but actually increased glycerol-mediated gluconeogenesis via the direct pathway. Suppression of glycerol kinase or overexpression of glycerol-3-phosphate phosphatase markedly reduced glycerol-mediated glucose production from both the direct and mitochondrial pathways, but did not reduce glucose concentrations in fasted MPC knockout mice. These findings indicate that glycerol-mediated gluconeogenesis is not impaired in MPC-deficient hepatocytes and suggest that gluconeogenesis from other organs, likely kidney or intestine, compensates for loss of the hepatic MPC. Disclosure N.Yiew: None. G.J.Patti: None. S.C.Burgess: None. B.N.Finck: Advisory Panel; Cirius Therapeutics, Inc., Stock/Shareholder; Cirius Therapeutics, Inc. D.Ferguson: None. K.Cho: None. S.Deja: None. C.Jarasvaraparn: None. X.Fu: None. A.J.Lutkewitte: None. S.Mukherjee: None. J.M.Singer: None. Funding National Institutes of Health (R01DK104735, R01DK117657, T32DK007120, R35ES028365)