Blood Glucose Lowering Effect Research Articles

Lactic acid-fermented Sake lees protect against nonalcoholic steatohepatitis in mice

Background: Nonalcoholic steatohepatitis (NASH) is a common disease that may lead to hepatocellular carcinoma (HCC) through fatty liver and cirrhosis. Although the prevalence of NASH is increasing worldwide, there is no cure established thus far. Sake lees are a by-product of sake refining, with a known liver-protecting effect. Lactic acid-fermented sake lees (FSL) are a food produced by lactic acid fermentation and dealcoholization of sake lees. This product is commercially available in Japan. Although FSL has been associated with numerous functions, thus far, studies have not investigated its hepatoprotective effect. Objectives: The objectives of this study are to evaluate the hepatoprotective effects of lactic acid-fermented sake lees (FSL) in a mouse model of NASH-HCC, to assess the impact of FSL supplementation on blood glucose levels in mice with NASH, to analyze the expression of inflammatory markers in FSL-fed mice compared to controls, and to determine the overall efficacy of FSL in inhibiting the progression of NASH. Methods: For this study, we established a mouse model of NASH-HCC. Mice were placed on a high-fat diet supplemented with FSL from 10 to 14 weeks of age. We assessed the diet's efficacy in halting NASH progression compared to a control group. Results: The group fed with FSL exhibited a significant suppression in blood glucose levels and a notable inhibition of NASH progression compared to the control group. Protein analysis revealed a reduction in the expression of inflammatory markers in the FSL-fed group compared to controls. Conclusion: Ingestion of FSL may exert anti-inflammatory and blood glucose-lowering effects and inhibit NASH progression. Keywords: anti-inflammation, blood glucose, fatty liver, Sake lees

HPLC-MS/MS Method for the Quantitative Determination of Metformin in Rat Plasma and Its Application to Comparative Bioavailability Assessment

Background: Metformin is a biguanide derivative utilized as a first-line treatment for type 2 diabetes for people over 60 years. However, it faces certain limitations due to its incomplete absorption, resulting in a 50-60% bioavailability. In addition to its blood glucose-lowering effect, the antiproliferative effect of metformin has been demonstrated in vitro. Therefore, it is necessary to consider alternative administration routes that can enhance the bioavailability of metformin, expanding its clinical use beyond its role as an antidiabetic agent. Objective: The aim of the study was to develop a reliable bioanalytical method for the quantitation of metformin in male Sprague-Dawley rat plasma and explore the promising alternative administration route for metformin use. Methods: A robust, high-performance liquid chromatography-tandem mass spectrometry method for the quantification of metformin in rat plasma was developed and validated according to the latest regulatory guidance for bioanalysis. Results: Based on the area under the curves obtained from the rat pharmacokinetic study, subcutaneous injection increased the systemic exposure of metformin by 1.79-fold compared to oral administration in rats. Conclusion: Subcutaneous administration of metformin enhances its bioavailability compared to oral administration, leading to increased antidiabetic effects and potential antitumor activity.

Empagliflozin protective effects against cisplatin-induced acute nephrotoxicity by interfering with oxidative stress and inflammation in Wistar rats.

Cisplatin (Cis) is a platinum-based antineoplastic drug used in various types of cancers. This drug can induce nephrotoxicity as a cause of acute kidney injury (AKI) by inducing oxidative stress and inflammation. Empagliflozin (Empa) is a newly developed inhibitor of sodium-glucose cotransporter-2 (SGLT2) approved as an antidiabetic medication for patients with type 2 diabetes mellitus. In addition to its blood glucose-lowering effect, Empa has been shown to exert anti-inflammatory and anti-oxidant properties. The current study aimed to investigate the protective effects of Empa on Cis-induced nephrotoxicity in rats. Male Wistar albino rats were divided into five groups, each of six rats: Sham group (received vehicle for 7 days), Control group (received vehicle for 7 days and Cis injection on day 2), Cis + Empa10 (received 10mg/kg Empa for 7 days and Cis injection on day 2), Cis + Empa30 (received 30mg/kg Empa for 7 days and Cis injection on day 2) and, Empa 30 (received 30mg/kg Empa for 7 days). One day after the last injection in each group, rats were weighed and then sacrificed to analyze the hematological, biochemical, and histological parameters. Cis markedly increased levels of inflammatory parameters such as renal tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and myeloperoxidase (MPO) activity. Notably, malondialdehyde (MDA), blood urea nitrogen (BUN), and creatinine levels were enhanced after Cis administration. Also, the chemotherapeutic agent significantly reduced antioxidant indicators such as renal catalase (CAT), glutathione peroxidase (GpX), and superoxide dismutase (SOD). Furthermore, histopathological examinations also revealed severe renal damage following Cis treatment which was improved by Empa administration. Empa treatment at both doses (10 mg/kg and 30 mg/kg) reversed Cis-induced changes in all the above renal parameters. In conclusion, Empa has protective effects on Cis-induced nephrotoxicity by inhibition of oxidative stress and inflammation.

Lipid- and glucose-lowering effects of Rhamnan sulphate from Monostroma nitidum with altered gut microbiota in mice.

Rhamnan sulphate (RS) is a sulphated polysaccharide found in green algae such as Monostroma nitidum that exhibits various biological functions, including anticoagulant, antitumour, antiviral, and anti-obesity properties. In our previous clinical trial, we demonstrated that RS intake improves constipation. However, no specific bacteria showed a significant (p < .05) change. Notably, these results were obtained after a short RS inoculation period of only 2 weeks. In the present study, to evaluate the long-term effects of RS on the gut microbiota, we orally administered RS to BALB/c mice for 11 weeks, analyzed their blood biochemical data, and performed 16s rRNA-sequencing. Oral administration of RS increased body weight with increased food intake, whereas plasma total cholesterol and fasting plasma glucose levels decreased. RS-fed mice showed lower fasting insulin levels (p < .1) and decreased homeostatic model assessment for insulin resistance (HOMA-IR, p < .0001), suggesting that RS improved insulin resistance. In the feces of mice, the amounts of acetic and propionic acids increased. In the gut microbiota, predictive metagenomic profiling using the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) revealed functional alterations in Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways in RS-fed mice. Corresponding to the blood glucose-lowering effect, the glycolysis and tricarboxylic acid (TCA) cycle pathways were activated. In addition, the Firmicutes/Bacteroides (F/B) ratio, which may be associated with various health outcomes, was also reduced. These results suggest that the blood glucose-lowering effect, improvement in insulin resistance, and lipid-lowering effect of RS may be due to changes in the intestinal microbiota.

Immediate Impact of Switching from Dipeptidyl Peptidase4 (DPP4) Inhibitors to Low-Dose (0.3mg) Liraglutide on Glucose Profiles: A Retrospective Observational Study.

As treatment agents for diabetes, liraglutide is a long-acting glucagon-like peptide1 receptor agonist, and dipeptidyl peptidase4 (DPP4) inhibitors are widely used because of their safety and tolerability. Regular treatment with liraglutide has been reported to significantly reduce blood glucose levels, but the impact of low-dose (0.3mg) liraglutide on blood glucose levels immediately after treatment switching from a DPP4 inhibitor remains unknown. We conducted a single-arm, retrospective, observational study in 55 inpatients with type2 diabetes (T2D) to investigate the changes (Δ) in their blood glucose levels at six time points (6-point) from the day before (day-1) to the day after (day1) by switching the antidiabetic treatment from a DPP4 inhibitor to liraglutide 0.3mg (low-dose liraglutide) once daily. We also attempted to identify factors associated with the blood glucose-lowering effects of liraglutide. The median values of the changes in fasting, preprandial, and postprandial blood glucose levels and the fluctuations in the blood glucose levels expressed as the standard deviation of the 6-point blood glucose levels were significantly lower on day1 than on day-1 (P < 0.05, P < 0.0001, P < 0.0001, P < 0.01, respectively); there were no cases of severe hypoglycemia. The Δblood glucose levels were not associated with the baseline serum hemoglobin A1c values or with any markers of the insulin secreting capacity. There were no associations between the previously used blood glucose-lowering drug and the Δblood glucose levels. Switching from a DPP4 inhibitor to low-dose (0.3mg) liraglutide once daily significantly reduced the blood glucose levels and excursions of the blood glucose levels even from the very day after the treatment switch, with no serious adverse events.

Impact of Dapagliflozin on Atherosclerosis through Inflammation and Oxidative Pathways

Background: Atherosclerosis is a prevalent pathological disorder considered a leading cause of death globally. The pathological process is characterized by fat deposition in the blood vessels, ultimately developing plaques. The atherosclerotic plaque was the final result of the inflammatory reaction and oxidative pathway. Dabagliflozine is a member of hypoglycemic drugs that are classified based on their action as Na-glucose co-transporter 2 inhibitors. Dabagliflozine, besides its blood glucose-lowering effects, may also exhibit cardiovascular protection by reducing oxidative damage. Our research aimed to evaluate how the drug (dabagliflozine) interacted with inflammation and oxidative processes to impact atherosclerosis. Materials and Methods: In this study, eighteen male mice were split into three groups: one fed a regular diet, one fed a cholesterol-rich diet, and one fed a cholesterol-rich diet with dapagliflozin. Blood samples were taken regularly over twelve weeks to analyze serum markers such as TNF-α, endothelin-1, and lipid levels. Results: Initially, there were no significant differences in serum markers among the groups. However, after twelve weeks, the mice treated with dapagliflozin showed notable reductions in TNF-α and endothelin-1 levels (though statistically insignificant). Moreover, there were significant improvements in HDL (the "good" cholesterol) levels, and significant decreases in VLDL and TG (triglycerides) levels (P&lt;0.05). Total cholesterol (TC) and LDL (the "bad" cholesterol) levels also decreased, although not significantly. Conclusion: In conclusion, dapagliflozin demonstrated promising protective effects against atherosclerosis in mice by regulating inflammatory cytokine production and improving lipid profiles. These findings suggest that dapagliflozin may have potential therapeutic benefits in managing cardiovascular disease by targeting both inflammation and lipid metabolism. However, further research is needed to validate these results and explore the drug's effectiveness in humans.

Efficacy and safety of enavogliflozin vs. dapagliflozin as add-on therapy in patients with type 2 diabetes mellitus based on renal function: a pooled analysis of two randomized controlled trials

BackgroundWe assessed the efficacy and safety of enavogliflozin (0.3 mg), a newly developed SGLT-2 inhibitor, in patients with type 2 diabetes mellitus based on kidney function via pooled analysis of two 24-week, randomized, double-blind phase III trials.MethodsData from 470 patients were included (enavogliflozin: 0.3 mg/day, n = 235; dapagliflozin: 10 mg/day, n = 235). The subjects were classified by mildly reduced (60 ≤ eGFR < 90 mL/min/1.73 m², n = 247) or normal eGFR (≥ 90 mL/min/1.73 m², n = 223).ResultsIn the mildly reduced eGFR group, enavogliflozin significantly reduced the adjusted mean change of HbA1c and fasting plasma glucose levels at week 24 compared to dapagliflozin (− 0.94% vs. −0.77%, P = 0.0196). Enavogliflozin exhibited a more pronounced glucose-lowering effect by HbA1c when combined with dipeptidyl peptidase-4 inhibitors than that observed in their absence. Enavogliflozin showed potent blood glucose-lowering effects regardless of renal function. Conversely, dapagliflozin showed a significant decrease in the glucose-lowering efficacy as the renal function decreased. Enavogliflozin showed a higher urinary glucose excretion rate in both groups. The homeostatic model assessment showed that enavogliflozin markedly decreased the insulin resistance. The blood pressure, weight loss, or homeostasis model assessment of beta-cell function values did not differ significantly between enavogliflozin and dapagliflozin. Adverse events were similar between both drugs.ConclusionsThe glucose-lowering efficacy of enavogliflozin is superior to that of dapagliflozin in patients with type 2 diabetes mellitus with mild renal function impairment; this is attributed to its potent urinary glucose excretion-promoting ability. The emergence of new and potent SGLT-2 inhibitors is considered an attractive option for patients with inadequate glycemic control and decreased renal function.Trial registrationNot applicable (pooled analysis).

Liver-derived extracellular vesicles improve whole-body glycaemic control via inter-organ communication.

Small extracellular vesicles (EVs) are signalling messengers that regulate inter-tissue communication through delivery of their molecular cargo. Here, we show that liver-derived EVs are acute regulators of whole-body glycaemic control in mice. Liver EV secretion into the circulation is increased in response to hyperglycaemia, resulting in increased glucose effectiveness and insulin secretion through direct inter-organ EV signalling to skeletal muscle and the pancreas, respectively. This acute blood glucose lowering effect occurs in healthy and obese mice with non-alcoholic fatty liver disease, despite marked remodelling of the liver-derived EV proteome in obese mice. The EV-mediated blood glucose lowering effects were recapitulated by administration of liver EVs derived from humans with or without progressive non-alcoholic fatty liver disease, suggesting broad functional conservation of liver EV signalling and potential therapeutic utility. Taken together, this work reveals a mechanism whereby liver EVs act on peripheral tissues via endocrine signalling to restore euglycaemia in the postprandial state.

BLOOD GLUCOSE LOWERING EFFECT OF ETHANOL LEAF EXTRACT OF HYMENODICTYON FLORIBUNDUM (RUBIACEAE)

In developing countries, and some developed nations, diseases are managed using complementary medicine with the aid of preparations from a single or mixture of herbs. Diabetes mellitus, described by persistently high blood glucose levels, owing to abnormalities in insulin secretion, is among such disorders. Hymenodictyon floribundum has been reported to be used in ethnomedicine to manage diabetes. This study aimed to investigate the blood glucose-lowering activity of the ethanol extract of Hymenodictyon floribundum leaves in adult Wistar rats. Elemental analysis, preliminary phytochemical screening, and acute toxicity test were carried out. Oral glucose tolerance test (OGTT) was performed using five groups of adult Wistar rats administered graded doses (375, 750, and 1500 mg/kg) of the extract, distilled water (1 mL/kg) as negative control, and metformin (500 mg/kg) as positive control. Measurement of glucose levels in blood was performed at 0, 30, 60, and 120 minutes of extract administration, respectively. The result of the elemental analysis indicated the presence of Ca, Mg, K, Na, Fe, Mn, Cu, Cr, Ni, and Pb. Preliminary phytochemical screening revealed tannins, steroids, triterpenes, saponins, alkaloids, anthraquinones, and flavonoids. The Median lethal dose (LD50) of the extract was estimated to be higher than 5000 mg/kg orally. The animals treated with the extract showed a significant (p&lt;0.05) decrease in blood glucose levels compared to the negative control. Blood glucose levels dropped below baseline in the animals treated with the highest dose (1500 mg/kg) of the extract. The study therefore revealed that Hymenodictyon floribundum has the potential to produce a blood glucose-lowering effect and corroborates the claim of antidiabetic activity of the plant.

BLOOD GLUCOSE LOWERING EFFECT OF ETHANOL LEAF EXTRACT OF HYMENODICTYON FLORIBUNDUM (RUBIACEAE)

In developing countries, and some developed nations, diseases are managed using complementary medicine with the aid of preparations from a single or mixture of herbs. Diabetes mellitus, described by persistently high blood glucose levels, owing to abnormalities in insulin secretion, is among such disorders. Hymenodictyon floribundum has been reported to be used in ethnomedicine to manage diabetes. This study aimed to investigate the blood glucose-lowering activity of the ethanol extract of Hymenodictyon floribundum leaves in adult Wistar rats. Elemental analysis, preliminary phytochemical screening, and acute toxicity test were carried out. Oral glucose tolerance test (OGTT) was performed using five groups of adult Wistar rats administered graded doses (375, 750, and 1500 mg/kg) of the extract, distilled water (1 mL/kg) as negative control, and metformin (500 mg/kg) as positive control. Measurement of glucose levels in blood was performed at 0, 30, 60, and 120 minutes of extract administration, respectively. The result of the elemental analysis indicated the presence of Ca, Mg, K, Na, Fe, Mn, Cu, Cr, Ni, and Pb. Preliminary phytochemical screening revealed tannins, steroids, triterpenes, saponins, alkaloids, anthraquinones, and flavonoids. The Median lethal dose (LD50) of the extract was estimated to be higher than 5000 mg/kg orally. The animals treated with the extract showed a significant (p&lt;0.05) decrease in blood glucose levels compared to the negative control. Blood glucose levels dropped below baseline in the animals treated with the highest dose (1500 mg/kg) of the extract. The study therefore revealed that Hymenodictyon floribundum has the potential to produce a blood glucose-lowering effect and corroborates the claim of antidiabetic activity of the plant.

Pharmacological screening of antidiabetic activity of ethanolic extracts of justicia tranquebarensis on streptozocin induced rats.

Non-communicable diseases like diabetes mellitus are becoming major health problem these days. There is an increasing demand by patients to use the natural products (plants) with anti-diabetic activity due to the severe side effects associated with the use of insulin and oral anti-diabetic drugs. One such plant is Justicia tranquebareinsis which has been traditionally used for the treatment of diabetes mellitus. The aim of this study was, therefore, to evaluate hypoglycemic activity of ethanol extract of Justicia tranquebareinsis in streptozotocin-induced diabetic rats, respectively and to carry out acute toxicity test. Two doses (200 mg/kg and 400 mg/kg) of the ethanol extract of Justicia tranquebareinsis were administered to normal glucose loaded and diabetic rat to study blood glucose lowering effect. Ethanol extract of Justicia tranquebareinsis (200mg/kg and 400mg/kg, p.o.) showed significant tolerance (P &lt; 0.05) to oral glucose load at 1 and 2 hrs after glucose load. The extract also produced significant (P &lt; 0.05) blood glucose reduction at 4 hours after its administration in normoglycemic mice. The extract at 400mg/kg dose level produced significant (P &lt; 0.05) reduction in blood glucose level at 2, 3 and 4 hours of treatment in streptozotocin (45 mg/kg) induced diabetic mice. Acute oral toxicity studies of ethanol extract of Justicia tranquebareinsis in rats showed no death or signs of toxicity at the dose of 2000 mg/kg indicating the safety nature of the extract. The results of the experiments showed that ethanol extract of Justicia tranquebareinsis has significant antihyperglycemic activity in streptozotocin induced diabetic rat and improvement in glucose tolerance and slight hypoglycemic activity in normal rat justifying the traditional claim for its use in diabetes.

Sodium orthovanadate exhibits anti-angiogenic, antiapoptotic and blood glucose-lowering effect on colon cancer associated with diabetes.

The presence of type 2 diabetes mellitus increases the risk of developing the colon cancer. The main objective of this study was to determine the role of sodium orthovanadate (SOV) in colon cancer associated with diabetes mellitus by targeting the competitive inhibition of PTP1B. For in vivo study, high fat diet with low dose streptozotocin model was used for inducing the diabetes mellitus. Colon cancer was induced by injecting 1,2-dimethylhydrazine (25mg/kg, sc) twice a week. TNM staging and immunohistochemistry (IHC) was carried out for colon cancer tissues. In vitro studies like MTT assay, clonogenic assay, rhodamine-123 dye assay and annexin V-FITC assay using flow cytometry were performed on HCT-116 cell line. CAM assay was performed to examine the anti-angiogenic effect of the drug. Sodium orthovanadate reduces the blood glucose level and tumor parameters in the animals. In vitro studies revealed that SOV decreased cell proliferation dose dependently. In addition, SOV induced apoptosis as depicted from rhodamine-123 dye assay and annexin V-FITC assay using flow cytometry as well as p53 IHC staining. SOV showed reduced angiogenesis effect on eggs which was depicted from CAM assay and also from CD34 and E-cadherin IHC staining. Our data suggest that SOV exhibits protective role in colon cancer associated with diabetes mellitus. SOV exhibits anti-proliferative, anti-angiogenic and apoptotic inducing effects hence can be considered for therapeutic switching in diabetic colon cancer.

Antihyperglycemic and Hypolipidemic Effect of Hydroalcoholic Extract of Dolichos lablab Linn in STZ induced Type 1 Diabetes Mellitus in Mice

Background: Traditional herbs have been used in the human healthcare system as medicines, foods, or spices from ancient times. Dolichos lablab is an Indian medicinal herb with a good source of nutrition, and has insulin-like proteins, thus can be employed in the cure of diabetes. Objective: This study aims to evaluate the lipids and blood glucose lowering effect of Dolichos lablab hydroalcoholic extract by using STZ-induced type 1 diabetes mellitus in-vivo model. Methods: Animals were divided into five groups including vehicle control, diabetic control, extract treated (200 &amp; 400 mg/kg), and standard group. All the treatment was continued for 14 days after the confirmation of diabetes. Food consumption, water intake, serum glucose, insulin, kidney function test, liver, and serum lipid profile were assessed to evaluate the antidiabetic potential of the plant. Results: Phytochemical analysis showed the presence of carbohydrates, alkaloids, flavonoids, protein, amino acids, and terpenoids. Extract treatment significantly diminished HbA1c, and blood glucose levels. In addition, an ameliorative effect on serum cholesterol, triglycerides, and lipoprotein was observed at 400 mg/kg/day dose. Moreover, blood urea nitrogen and hepatic SGPT were also reduced significantly with extract treatment. Conclusion: Therefore, the present study depicted that Dolichos lablab is a useful herb in diabetes management and possesses hypolipidemic potential.

Bioinspired fine-tuning of the mechanical rigidity of SNEDDS for the efficient crossing of multiple gastrointestinal barriers

Nanoproperties, such as size, charge, and rigidity, have been demonstrated to be crucial for nanovehicles to overcome numerous gastrointestinal obstacles. However, the facile approach of modifying the rigidity of nanovehicles remains scarce, limiting understanding of how rigidity impacts their oral delivery. Inspired by the fact that cellular phospholipid content regulates plasma membrane rigidity, the rigidity of self-nanoemulsifiying drug delivery system (SNEDDS) could be fine-tuned via phosphocholine content while their size and zeta potential remain unchanged, using insulin as a model drug. Notably, soft SNEDDS exerted longer gastrointestinal transit time, higher drug release rate, stronger gastrointestinal stability and relatively lower mucus permeation but superior epithelial transcytosis than their hard counterparts in a macropinocytosis-dependent manner. The rigidity-related enhanced transcytosis was attributed to improved endocytosis, lysosome escape capability and exocytosis. Rats with type 1 diabetes exhibited greater oral insulin absorption and blood glucose lowering effect with soft SNEDDS. This study demonstrated the regulatory role of phospholipids in nanovehicle rigidity, which could help develop mechanically optimized nanomedicines in the future.

Metformin and exercise effects on postprandial insulin sensitivity and glucose kinetics in pre-and-diabetic adults.

The potential interaction between metformin and exercise on glucose-lowering effects remains controversial. We studied the separated and combined effects of metformin and/or exercise on fasting and postprandial insulin sensitivity in individuals with pre- and - type 2 diabetes (T2D). Eight T2D adults (60±4 years) with overweight/obesity (32±4 kg·m-2) under chronic metformin treatment (9±6 years; 1281±524 mg·day-1) underwent four trials; a) taking their habitual metformin treatment (MET), b) substituting during 96 h their metformin medication by placebo (PLAC), c) placebo combined with 50 min bout of high-intensity interval exercise (PLAC+EX), and d) metformin combined with exercise (MET+EX). Plasma glucose kinetics using stable isotopes (6,6-2H2 and [U-13C] glucose), and glucose oxidation by indirect calorimetry, were assessed at rest, during exercise, and in a subsequent oral glucose tolerance test (i.e., OGTT). Postprandial glucose and insulin concentrations were analyzed as mean and incremental area under the curve (iAUC), and insulin sensitivity was calculated (i.e., MATSUDAindex and OGISindex). During OGTT, metformin reduced glucose iAUC (i.e., MET and MET+EX lower than PLAC and PLAC+EX, respectively; P=0.023). MET+EX increased MATSUDAindex above PLAC (4.8±1.4 vs 3.3±1.0, respectively; P=0.018) and OGISindex above PLAC (358±52 vs 306±46 mL·min-1·m-2, respectively; P=0.006). Metformin decreased plasma appearance of the ingested glucose (Ra OGTT; MET vs PLAC, -3.5; 95% CI -0.1 to -6.8 µmol·kg-1·min-1; P=0.043). Metformin combined with exercise potentiates insulin sensitivity during an OGTT in individuals with pre- and - type 2 diabetes. Metformin's blood glucose-lowering effect seems mediated by decreased oral glucose entering the circulation (gut-liver effect) an effect partially blunted after exercise.

A Pilot Crossover Study of Berberine and its Short-Term Effects on Blood Glucose Levels in Healthy Volunteers

Introduction: Different berberine preparations were evaluated for their effectiveness on lowering blood glucose in a pilot, open-label, crossover study conducted in healthy adults. Methods: Fourteen healthy volunteers of both sexes were recruited, and seven completed all treatments in the study. Study participants ingested one of three berberine preparations containing 500mg of berberine, respectively. A one week wash out period was included between treatments. A control group was included to measure the participants’ baseline response to a 75g glucose solution without any treatment. The following interventions were administered: berberine powder in hard gelatin capsules, berberine in an oil matrix encapsulated in soft-gelatin capsules, and berberine in LipoMicel® matrix encapsulated in soft-gelatin capsules. Blood glucose concentrations in each participant were monitored from pre-dose baseline, before the capsules were ingested, until up to 3 hours after the capsules were ingested. Results: LipoMicel Berberine treatment led to reduced blood glucose concentrations Area Under Curve (AUC, mean difference: 1.57; 95% CI: 0.021 – 3.12; P = 0.046; Cohen’s d = 1.53) and reduced maximum glucose concentration (Gmax, mean difference: 1.07; 95% CI 0.004 – 2.14; P = 0.049; Cohen’s d = 1.52) compared to the control group when no-treatment was given. No adverse events related to berberine treatments were reported by participants throughout the study period. Conclusions: LipoMicel Berberine was effective in lowering blood glucose levels by 12% after two 500mg doses. Berberine in other formulations may require a longer dosing regimen before blood glucose lowering effects can be demonstrated.

Solid lipid Lyo-Nanosuspension: A promising stabilized oral delivery system for the antihyperglycemic extract of mistletoe Plicosepalus acacia

The antihyperglycemic effect of Plicosepalus acaciae (P. acaciae) extract was proven, but it still needs to be formulated into a suitable dosage form. We aimed at preparing an oral stabilized SLNs for P. acaciae with high payload, to be used as powder for reconstitution, filled into capsule or compressed into tablet. SLNs were prepared by emulsion solvent evaporation technique. Preliminary characterization was performed followed by full assessment of the optimized SLNs suspension and/or its lyophilized form: particle size, zeta potential, surface morphology, percentage entrapment efficiency (% EE), DSC, FTIR and in vitro release studies. The optimized SLNs lyophilized formula (F3L) exhibited acceptable compressibility and flowability. The reconstituted F3L showed % sedimentation volume of 91.83 %, re-dispersibility of 95%, viscosity of 764.33 cp, uniform particle size of 30.28 nm as shown by TEM, polydispersity index (PDI) of 0.16, zeta potential of −36.4 mV, % EE of 89.64 % and drug content of 97.69 %. The physical mixture and F3L FTIR spectrum indicated compatibility of components. In vitro release study showed a burst release in lyophilized formulations followed by slow-release, calculated as total phenolic content. Our previously reported work revealed that the total extracts of P. acaciae and SLNs formulations with the greatest lipid content F3s, demonstrated a considerable blood glucose-lowering effect in diabetic rats. The obtained lyophilized SLNs is promising for preparation of a suitable stable dosage form for P. acaciae extract to be used in treatment of diabetes.

291-OR: CREG1 Regulates Hepatic Insulin Sensitivity and Insulin Receptor Trafficking

CREG1 is a small glycoprotein in the endosomal-lysosomal system involved in endocytic trafficking. It contains 3 N-linked glycosylation sites and is highly expressed in the liver. To elucidate its physiological functions, we generated Creg1fl/fl mice using CRISPR technology. Whole-body and hepatocyte-specific deletion of Creg1 was achieved by crossing Creg1fl/fl with UBC-cre-ERT2 and Albumin-cre mice, respectively. Both knockout mice developed elevated glycemia, glucose intolerance, and resistance to the blood glucose-lowering effect of insulin. Loss of hepatic CREG1 also aggravated high-fat diet-induced insulin resistance and hyperinsulinemia. This is likely caused by impaired insulin receptor (IR) trafficking because IR expression on the hepatocyte surface was significant reduced in hepatocyte specific Creg1 knockout mice. In in vitro studies using cultured hepatocytes, CREG1 overexpression increased IR recycling to the cell surface and enhanced insulin signaling, whereas its knockdown had the opposite effect. These findings indicate a cell autonomous role of CREG1 in hepatocyte IR trafficking and insulin signaling. Furthermore, SNP database survey identified 3 missense mutations of CREG1 at the N216 glycosylation site (N216I, N216K, and N216Y). When overexpressed in human hepatocytes, the N216I mutant inhibited insulin signaling in a dominant negative fashion. Taken together, these results suggest CREG1 regulates hepatic insulin sensitivity and signaling likely through its effect on IR trafficking. CREG1 glycosylation at N216 may be required for its function in these processes. Disclosure Y.Qi: None. J.Liu: None. J.C.Chao: None. S.A.Rahimi: None. L.Y.Lee: Speaker's Bureau; Abbott. S.Li: None. Funding Rutgers Biomedical and Health Sciences

Co-administration of metformin and vitamin C or E in improves diabetes prognosis in streptozotocin-induced diabetes rats

The prevalence of diabetes mellitus has increased astronomically in recent years. This has resulted in increased disease adjusted life years (DALYs), mortality and decrease in life expectancy. Some of the fall outs of diabetic disease in patients include hyperlipidaemia, oxidative stress, renal and hepatic dysfunction. This study investigated the combined effects of metformin with either vitamin C or E on hyperglycemia-induced hyperlipidemia, oxidative stress, renal and hepatic dysfunction. Diabetes mellitus was induced in the animals fasted overnight with a single dose of streptozotocin (40 mg/kg, intraperitoneal). Animals with fasting blood glucose (FBG) levels &gt;200 mg/dl after 48 hours of streptozotocin administration were marked diabetic and were randomly grouped into 6 groups of 5 diabetic rats each. Treatments were administered orally once daily for two weeks. FBG levels, and other parameters were determined. The results showed that the various treatments significantly and comparably reduced the FBG levels on both day 7 (p&lt;0.05, P&lt;0.01) and day 14 (p&lt;0.001). All the treatments significantly reduced hyperglycemia-induced increase in the levels of triglyceride (TG), total cholesterol (TC), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine and malondialdehyde (MDA). The antioxidant enzyme activity of superoxide dismutase (SOD), glutathione reductase (GSH), and catalase (CAT) was enhanced by the combined effects of metformin and vitamin C or E. Vitamin E and combination of metformin and vitamin E did not prevent diabetes induced-weight loss throughout the study compared to diabetic control. The findings have demonstrated that metformin and vitamin C co-administration exhibits synergistic effects on blood glucose lowering effect, antioxidant activity and potential advantage of preventing multi-organ damaging effects of type 2 diabetes.

The Effectiveness of Red Ginger Extract (Zingiber Officinale Var. Rubrum) on Decreased Blood Glucose Levels in Mice (Mus Musculus)

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia conditions (increased blood glucose) caused by abnormalities in insulin secretion, abnormalities in the action of insulin or perhaps both. Red Ginger (Zingiber officinale var. rubrum) contains alkaloids, flavanoids, tannins, saponins, gingerol and shagol which have blood glucose-lowering, anti-inflammatory, anticancer and antitumor effects. This study aims to determine the effectiveness of Red Ginger extract against decreasing blood glucose levels in mice (Mus musculus). This research is a type of experimental study conducted to determine the effectiveness of red ginger extract against decreasing blood glucose levels in mice. This study was conducted using alloxane as a diabetes inducer, Na CMC 1% as a negative control, glibenclamide as a positive control, extract dose 2 %, 5 % and 7 % orally for 7 days in 5 groups of test animals. The results of the study obtained 1% Na-CMC results showed a percentage decrease, namely -16.32% and -103.03%. In the group of mice given Red Ginger extract 2% showed a percentage decrease, namely 105.57% and 102.04%. The group of mice given Red Ginger extract 5% showed a percentage decrease of 105.83% and 86.84%. The group of mice given 7% Red Ginger extract showed a percentage decrease, namely 67.34% and 97.45%. The group of mice suspended by glibenclamide showed a percentage decrease of 73.05% and 66.66%. It can be concluded that the administration of Red Ginger extract has been shown to reduce blood glucose levels in aloxane-induced mice at concentrations of 2%,5% and 7% with significant values (p &lt; 0.05) indicating a difference and obtained the most effective concentration in lowering blood glucose levels in mice (Mus musculus) is a concentration of 7%.