Decreased Fasting Blood Glucose Levels Research Articles

Long-term consumption of the sugar substitute sorbitol alters gut microbiome and induces glucose intolerance in mice

AimsEpidemic obesity and diabetes have led to increased use of low-calorie sweeteners. Although several studies have suggested that consumption of artificial sweeteners, such as aspartame and saccharin, might have negative effects, the potential impacts of natural sweeteners on human health remain largely unknown. Main methodsThe deferential effects of short term and long term consumption of sorbitol on glucose homeostasis in mice by oral gavage. The glucose homeostasis and utility were evaluated by both oral or intraperitoneal glucose tolerance tests. Insulin levels were determined using enzyme-linked immunosorbent assay. Changes of gut microbiome were evaluated by 16S rRNA gene sequencing, and analyzed by principal components analysis. Key findingsBolus feeding of sorbitol by gavage significantly increased plasma insulin concentrations and decreased fasting blood glucose levels. Intriguingly, long-term sorbitol gavage for four weeks showed no significant effects on intraperitoneal glucose tolerance test outcomes, but it induced glucose intolerance according to the oral glucose tolerance test. Thus, we tested whether long-term sorbitol gavage might alter the relative abundances of gut microbiome constituents in mice. Principal components analysis indicated that long-term sorbitol intake indeed caused significant changes to the gut microbiome. In particular, we found that long-term sorbitol intake significantly decreased the relative abundances of Bifidobacterium, Lachnospiraceae UCG 001, Lachnospiraceae NK4A136, Eubacterium ventriosum, Candidatus Arthromitus, and Ruminococcus torques. We also found that long-term sorbitol increased the relative abundances of Helicobacter, Tyzzerella, Alistipes, and Prevotella 9. SignificanceLong-term sorbitol consumption may change the composition of the gut microbiome and potentially induce glucose intolerance.

Moderate-intensity Treadmill And Ergocycle Exercise Reduce Fasting Blood Glucose Levels In Obese Women

The study aimed to analyze the decrease in fasting blood glucose levels after moderate-intensity treadmills and ergocycle exercise in obese women. The quasi-experiment method used in this study with two groups pretest-posttest design design. A total of 20 obese women aged 19-23 years participated in the study and were divided into two groups, namely acute ergocycle exercise (AEE, n=10), and acute treadmill exercise (ATE, n=10). Exercise is done a single session with an intensity of 60-70% HRmax for 40 minutes using ergocycle (Monark 828 E) and Richter Treadmill (4.0 HP DC). Blood collection is done 30 minutes pre-exercise and 5 minutes post-exercise on capillary blood vessels in the fingerstick. Measurement of fasting blood glucose levels is done using Accu-Chek Performance (Roche, Mannheim, Germany). Data analysis using Independent Samples T-Test with SPSS version 21. The results found that mean of the fasting blood glucose level pre-exercise on AEE (97.80?2.20 mg/dL), ATE (95.60?3.86 mg/dL), and (P>0.05). Mean of post-exercise fasting blood glucose levels on AEE (93.30?3.09 mg/dL), ATE (84.60?6.28 mg/dL), and (P<0.001). Mean of delta fasting blood glucose levels in AEE (?4.50?2.95 mg/dL), ATE (?11.00?6.99 mg/dL), and (P<0.05). Based on the results of research it can be concluded that ergocyle and treadmill exercise with moderate-intensity lowers fasting blood glucose levels. But treadmill exercise is more effective in lowering fasting blood glucose levels than ergocycle exercise. Future research is recommended to compare moderate-intensity treadmill exercise vs. moderate-intensity resistance exercise against decreased fasting blood glucose levels in obese women

Effectiveness of carbohydrate counting and Dietary Approach to Stop Hypertension dietary intervention on managing Gestational Diabetes Mellitus among pregnant women who used metformin: A randomized controlled clinical trial

Gestational diabetes mellitus (GDM) is one of the most common complication of pregnancy that has significant impacts on both mother and her offspring health. The present study aimed to examine the effect of carbohydrate counting, carbohydrate counting combined with DASH, and control dietary interventions on glycemic control, and maternal and neonatal outcomes. A total of 75 pregnant women with GDM at 24th - 30th week of gestation were enrolled and randomized to follow one of the three diets: control or carbohydrate counting, or carbohydrate counting combined with Dietary Approach to Stop Hypertension (DASH). Only 70 of them completed the study until delivery. Fasting blood samples were taken at baseline and the end of the study to measure fasting blood glucose (FBG), fasting insulin, glycated hemoglobin (HbA1c), and fructosamine. Homeostatic model assessment-insulin resistance (HOMA-IR) score was calculated using HOMA2 calculator program. The participants recorded at least four blood glucose readings per day. Maternal and neonatal outcomes were collected from medical records. Dietary intake was assessed by three-day food records at the baseline and the end of the study. Adherence to the three dietary interventions, resulted in decreased FBG levels significantly among all the participants (P<0.05). Consumption of the carbohydrate counting combined with the DASH diet showed significant reduction in serum insulin levels and HOMA-IR score compared to carbohydrate counting group and control group. Means of fructosamine and HbA1c did not differ significantly among the three intervention diet groups. Overall mean of 1-h postprandial glucose (1h PG) level was significantly lower in the carbohydrate counting combined with DASH group compared with that in the carbohydrate counting group and the control group (P<0.001). The number of women who were required to commence insulin therapy after dietary intervention was significantly lower in carbohydrate counting group and carbohydrate counting combined with DASH group (P=0.026). There were no significant differences in other maternal and neonatal outcomes among the three dietary intervention groups. The carbohydrate counting and the carbohydrate counting combined with DASH dietary interventions resulted in beneficial effects on FBG and 1h PG compared with the control diet. The three dietary interventions produced similar maternal and neonatal outcomes in women with GDM. This trial was registered on ClinicalTrials.gov under the identification code: NCT03244579. https://clinicaltrials.gov/ct2/show/NCT03244579.

Intravenous Wharton's Jelly stem cell increased the number of ? cells pancreas and reduced the fasting blood glucose level in diabetes mellitus Wistar rat male (Rattus norvegicus)

Introduction: Diabetes mellitus is a metabolic disease characterized by hyperglycemic and disorders of carbohydrate, protein and fat metabolism due to abnormalities in insulin secretion, insulin sensitivity or both. Based on previous research, Wharton's Jelly's mesenchymal stem cells have anti-inflammatory, immunoregulatory properties that can improve metabolic control and have the ability to differentiate into pancreatic lineage cells that function as insulin-producing cells in vitro culture. The purpose of this study was to prove that administration of mesenchymal stem cells Wharton's Jelly can increase the number of pancreatic beta cells and reduce fasting blood glucose levels in male rats (Rattus norvegicus) Wistar strain of diabetes mellitus.Methods: The research design used was pure experimental with post-test only control group design using 36 white male rats. All samples were induced with Streptozotocin and Nicotinamide. The selected samples were divided into two groups: the control group given glibenclamide + 0.9% NaCl, and the treatment group was given glibenclamide + mesenchymal stem cells from Wharton's Jelly. Calculation of the number of pancreatic beta cells and measurement of blood glucose levels were carried out after 14 days of treatment.Result: The results showed that the treatment group had a higher number of pancreatic beta cells than the control group (105.17 ± 16.379 cells/field of view vs. 54.00 ± 11.366 cells/field of view) (p &lt;0.001). In addition, the treatment group had lower fasting blood glucose levels than the control group (109.06 ± 16.71 mg/dl vs 122.78 ± 10.14 mg / dl) (p &lt;0.05).Conclusion: It was concluded that intravenous administration of Wharton's Jelly mesenchymal stem cells increased the number of pancreatic beta cells and decreased fasting blood glucose levels in male rats (Rattus norvegicus) Wistar strain of diabetes mellitus.

Co-administration of metformin and gallic acid modulates JAK/STAT signaling pathway and glutathione metabolism in fructose-fed streptozotocin diabetic Rats

BackgroundIncidence of diabetes Mellitus (DM) is on the rise with each passing year in spite of available therapies in the management of DM. Metformin, a standard antidiabetic drug, and gallic acid (GA) are some of the compounds with established antidiabetic properties. However, there is dearth of information on their combination on JAK/STAT signaling pathway and glutathione metabolism in diabetic model. This study investigated the combined effect of metformin and GA on diabetic rats. MethodsForty male wistar rats were divided into 5 groups viz: diabetic control, normal control, Metformin (100 mg/kg), GA (100 mg/kg) and GA (100 mg/kg) + Metformin (100 mg/kg). Diabetes was induced by administration of 10% fructose for 14 days followed by injection of streptozotocin (40 mg/kg). The therapy was administered for a total of 21 days. The pancreatic mRNA expression of antioxidant genes (glutamate cysteine ligase catalytic subunits (GCLC), glutamate cysteine ligase modifier subunits (GCLM) and Glutathione Synthetase (GSS), inflammatory genes (tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and proteins of the Janus Kinase/ Signal Transducer and Activator of Transcription pathway (Janus Kinase (JAK), Signal Transducer and Activator of Transcription (STAT), were quantified using reverse-transcriptase polymerase chain reaction (RT-PCR). Metformin and GA were also docked with Insulin, GSS, and Janus Kinase 2 (JAK2) to determine their binding affinity. ResultsRats treated with co-administration of GA and metformin significantly (p < 0.05) decreased fasting blood glucose level in comparison with groups treated with gallic acid only and metformin only. The gene expression analysis shows that co-administering metformin and gallic acid protects the pancreas of STZ-induced rats by increasing glutathione production, alleviating inflammation (IL-1, IL-6, IFN-), and modulating the JAK/STAT signaling pathway though upregulation of GCLC, GCLM, GSS mRNA expression and IL-1, IL-6, TNF-α, JAK2, STAT3 and STA5 mRNA expression. ConclusionThis study showed that the combination therapy of metformin and GA modulated JAK/STAT pathway mediated by the cytokines, and replenished glutathione in the pancreas of diabetic rats.

Squalene decreased fasting blood glucose level of type ii diabetic rats

Squaleneis a chemical compound that has been reported to have antidiabetic activity. The present study aimed to investigate the effect of squalene on fasting blood glucose level (FBGL) in type 2 diabetic rats. Diabetes type II in rats was obtained by giving nicotinamide (120 mg/kg) before high dose streptozotocin (60 mg/kg) intraperitoneally. A total of 18 diabetic rats were divided into 3 groups and served once daily for 12 days as follows; Group I Aquades (Diabetic Control) 10 ml/kg, Group II (Metformin 45 mg/kg) and Group III (Squalene 160 mg/kg). FBGL was measured at day 0, day 6 and day 12. The results showed that FBGL in both Squalene- (194.67 ± 28.32 mg/dL) and Metformin- (178.50 ± 34.27 mg/dL) were significantly decreased after 12 days intervention compared to Diabetic Control-treated groups (438.33 ± 65.79 µmol/L) with p<0.001. This study concluded that squalene was able to decrease FBGL in type II diabetic rats.

Angiopoietin-like protein 8 (betatrophin) inhibits hepatic gluconeogenesis through PI3K/Akt signaling pathway in diabetic mice

Background & aimsAngiopoietin-like protein 8 (ANGPTL8) is a 198 amino-acid long, novel secreted protein that is mainly expressed in the liver and brown adipose tissues. At present, evidence supporting the involvement of ANGPTL8 in the regulation of glucose metabolism is inconclusive, along with its function in the liver. Previous studies mainly focused on the effect of ANGPTL8 on glucose metabolism in non-diabetic mice, and few relevant studies in diabetic mice exist. Therefore, this study aimed to investigate the role of ANGPTL8 on glucose homeostasis and elucidate the underlying mechanisms in diabetic mice. Methodsdb/db diabetic and high-fat diet/streptozotocin-induced diabetic mice were injected with adenovirus expressing ANGPTL8 through the tail vein. Blood glucose levels were measured and glucose, insulin, and pyruvate tolerance tests were performed. To explore the molecular mechanism by which ANGPTL8 regulates hepatic glucose metabolism and manipulate mouse ANGPTL8 expression levels both in vivo and in vitro based on adenoviral transduction, gain- and loss-of-function strategies were adopted. ResultsAdenovirus-mediated overexpression of ANGPTL8 decreased fasting blood glucose levels and improved glucose tolerance and insulin sensitivity in db/db and high-fat diet/streptozotocin-induced diabetic mice. ANGPTL8 knockdown yielded the opposite effects. ANGPTL8 was upregulated in the cAMP/Dex-induced hepatocyte gluconeogenesis model. Moreover, ANGPTL8 overexpression in primary hepatocytes and diabetic mouse livers inhibited the expression of gluconeogenesis-related genes, including PEPCK and G6PC, by activating the AKT signaling pathway and, thereby, reducing glucose production. Therefore, the results demonstrated that ANGPTL8 improved glucose metabolism via inhibition of hepatic gluconeogenesis in diabetic mice. ConclusionsCurrent findings highlight a critical role of hepatic ANGPTL8 in glucose homeostasis, suggesting that increased ANGPTL8 expression could be an underlying factor for the inhibition of hepatic gluconeogenesis, which could be targeted for the prevention and treatment of type 2 diabetes.

Adenosine A1 receptor is dispensable for hepatocyte glucose metabolism and insulin sensitivity

Hepatic insulin resistance (IR) and enhanced hepatic glucose production (HGP) are key features of type 2 diabetes (T2D), contributing to fasting hyperglycemia. Adenosine receptors (ARs) are G protein-coupled and expressed in hepatocytes. Here, we explored the role of hepatic Gi/o-coupled A1AR on insulin resistance and glucose fluxes associated with obesity. We generated a mouse model with hepatocyte-specific deletion of A1AR (A1LΔ/Δ), which was compared with whole body knockout of A1AR or A1AR/A3AR (both Gi-coupled). Selective deletion of hepatic A1AR resulted in a modest improvement in insulin sensitivity. In addition, HFD A1LΔ/Δ mice showed decreased fasting glucose levels. Hyperinsulinemic-euglycemic clamp studies demonstrated enhanced insulin sensitivity with no change in HGP in HFD A1LΔ/Δ mice. Similar to A1LΔ/Δ, fasting blood glucose levels were significantly reduced in whole body A1Δ/Δ and A1Δ/ΔA3Δ/Δ compared to wild-type mice. Taken together, our data support the concept that blocking hepatic A1AR may decrease fasting blood glucose levels without directly affecting hepatocyte glucose metabolism and insulin sensitivity.

Oleuropein Ameliorates Advanced Stage of Type 2 Diabetes in db/db Mice by Regulating Gut Microbiota.

Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of type 2 diabetes. However, the efficacy of OP on the advanced stage of type 2 diabetes has not been investigated, and the relationship between OP and intestinal flora has not been studied. Therefore, in this study, to explore the relieving effects of OP intake on the advanced stage of type 2 diabetes and the regulatory effects of OP on intestinal microbes, diabetic db/db mice (17-week-old) were treated with OP at the dose of 200 mg/kg for 15 weeks. We found that OP has a significant effect in decreasing fasting blood glucose levels, improving glucose tolerance, lowering the homeostasis model assessment–insulin resistance index, restoring histopathological features of tissues, and promoting hepatic protein kinase B activation in db/db mice. Notably, OP modulates gut microbiota at phylum level, increases the relative abundance of Verrucomicrobia and Deferribacteres, and decreases the relative abundance of Bacteroidetes. OP treatment increases the relative abundance of Akkermansia, as well as decreases the relative abundance of Prevotella, Odoribacter, Ruminococcus, and Parabacteroides at genus level. In conclusion, OP may ameliorate the advanced stage of type 2 diabetes through modulating the composition and function of gut microbiota. Our findings provide a promising therapeutic approach for the treatment of advanced stage type 2 diabetes.

Sweet potato (Ipomoea batatas L.) leaf polyphenols ameliorate hyperglycemia in type 2 diabetes mellitus mice.

The hypoglycemic effects and potential mechanism of sweet potato leaf polyphenols (SPLP) on type 2 diabetes mellitus (T2DM) were investigated. Results showed that oral administration of SPLP to mice could alleviate body weight loss, decrease fasting blood glucose levels (by 64.78%) and improve oral glucose tolerance compared with those of untreated diabetic mice. Furthermore, increased fasting serum insulin levels (by 100.11%), ameliorated insulin resistance and improved hepatic glycogen (by 126.78%) and muscle glycogen (increased by 135.85%) were observed in the SPLP treatment group. SPLP also could reverse dyslipidemia, as indicated by decreased total cholesterol, triglycerides, low density lipoprotein-cholesterol and promoted high density lipoprotein-cholesterol. Histopathological analysis revealed that SPLP could relieve liver inflammation and maintain the islet structure to inhibit β-cell apoptosis. A quantitative real-time polymerase chain reaction confirmed that SPLP could up-regulate the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3β signaling pathway to improve glucose metabolism and up-regulate the phosphatidylinositol 3-kinase/protein kinase B/glucose transporter 4 signaling pathway in the skeletal muscle to enhance glucose transport. This study provides useful information to support the application of SPLP as a natural product for the treatment of T2DM.

Effects of Triphala on Lipid and Glucose Profiles and Anthropometric Parameters: A Systematic Review.

Aim.The efficacy of triphala on lipid profile, blood glucose and anthropometric parameters and its safety were assessed.Methods.Databases such as PubMed, ScienceDirect, Web of Science, and Thai Library Integrated System (ThaiLIS) were systematically searched to review current evidence of randomized controlled trials (RCT) on triphala. RCTs investigating the safety and efficacy of triphala on lipid profile, blood glucose and anthropometric parameters were included. Study selection, data extraction, and quality assessment were performed independently by 2 authors.Results.Twelve studies on a total of 749 patients were included. The triphala-treated groups showed significantly reduced low-density lipoprotein-cholesterol, total cholesterol and triglyceride in 6 studies. Five RCTs demonstrated triphala-treated groups led to statistically significant decrease in body weight, body mass index and waist circumference of obese patients. Moreover, triphala significantly decreased fasting blood glucose level in diabetic patients but not in people without diabetes. No serious adverse event associated with triphala was reported during treatment.Conclusions.This review summarized a current evidence to show triphala might improve the lipid profile, blood glucose, the body weight, body mass index and waist circumference under certain conditions. However, large well-designed RCTs are required to confirm this conclusion.

Effects of honeybee (apis mellifera) venom on redox balance, biochemical and hematological profile in diabetic rats: A preliminary study

The treatment of diseases with honeybee venom (apitoxin) is a branch of apitherapy, which has yet to find substantial scientific support. In this present study, we used apitoxin to investigate its effects on diabetes mellitus (DM) in rats. The use of apitoxin injection on single-dose streptozotocin (STZ)-treated rat model was selected, and the study took 28 days. Fasting blood glucose (FBG) was measured weekly. Biochemical and hematological parameters, oxidative stress markers, and insulin levels were measured from the blood samples provided on the last day of the study, and the DNA damage marker (8-OHdG) was measured from urine samples. We found that apitoxin increased malondialdehyde (MDA) and carbonylated protein (PCO), and decreased glutathione (GSH) levels significantly. Additionally, apitoxin increased nitric oxide (NOx) levels significantly in diabetic rats. The findings suggest that apitoxin increases oxidative stress to some extent. Apitoxin had no significant effect on plasma insulin levels. Apitoxin apparently caused small decreases in FBG levels. Apitoxin appears to cause an increase in aspartate aminotransferase (AST), and an increase in the number of platelets (PLT) and granulocytes (GRAN) in diabetic rats. Consequently, the possible antidiabetic effect of apitoxin on DM could only be supported at the preliminary level and presented with speculation in this state of the study.

Investigation of the Effects of Difluorinated Curcumin on Glycemic Indices in Streptozotocin-Induced Diabetic Rats.

Curcumin is an antioxidant agent that improves glycemia in animal models of diabetes. Clinically curcumin use is limited due to poor solubility, weak absorption, and low bioavailability; therefore, this study to investigate the effects of curcumin's analog, difluorinated curcumin (CDF), on fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT), in streptozotocin (STZ)-induced diabetic rats was undertaken. STZ-induced diabetes rats were randomly assigned to six groups (7 rats per group). They were treated daily by oral gavage with curcumin (200 and 100mg/kg/day), CDF (200 and 100mg/kg/day), and metformin (200mg/kg/day) as a positive control group, for 4weeks. Two diabetic control (DC) and normal control (NC) groups (non-diabetic rats) received normal saline and citrate buffer, respectively. FBG was measured at the beginning and end of the treatment (Day 0 and week 4) and OGTT and ITT were performed to determine glucose tolerance and insulin sensitivity. Cur100, CDF 100, and CDF200 significantly decreased FBG levels after 4weeks oral administration by -34% (-150mg/dL±70, p=0.02), -36% (123mg/dL ±67, p<0.04), and -40% (-189mg/dL±91, p=0.03), respectively. Glucose sensitivity by OGTT showed a significant improvement in glucose tolerance ability in all treated groups compared with DC group. ITT demonstrated that insulin response improved significantly in Cur100 and CDF 200 groups. Overall, CDF improved glucose tolerance and insulin sensitivity, while reducing FBG compared to curcumin, suggesting that curcumin analogs may have therapeutic utility in diabetes.

Anti‐adipogenesis and metabolism‐regulating effects of heat‐inactivated Streptococcus thermophilus MN‐ZLW‐002

Metabolic syndrome and obesity have become serious threats to public health worldwide. This study was conducted to evaluate the anti-adipogenesis and metabolism-regulating effects of heat-inactivated Streptococcus thermophilus MN-ZLW-002 (MN-ZLW-002), which can be used as a yogurt starter. In vitro study suggested that MN-ZLW-002 stimulated the RAW264.7 macrophages to produce significant amounts of interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-α and induced intense phosphorylation of P38, p44/42 MAPK and nuclear factor κB. MN-ZLW-002-stimulated RAW264.7-conditioned medium (CM) notably suppressed the differentiation and adipogenesis of 3T3-L1 pre-adipocytes. The 12-week in vivo study suggested that orally administered MN-ZLW-002 significantly reduced the weight gain of mice caused by the high-fat diet (HFD) at weeks 3-8; decreased fasting blood glucose levels at week 4 and week 8; decreased serum total triglyceride level at week 12. MN-ZLW-002 also reduced serum IL-1β and chemokine ligand 3 levels in the HFD-fed mice. These findings suggest that heat-inactivated MN-ZLW-002 can suppress adipocytes differentiation and lipid accumulation by regulating the immune response, possibly via the release of cytokines, particularly TNF-α; MN-ZLW-002 can improve metabolism-related indicators in the early stage of HFD intervention and regulate the related pro-inflammatory immune response.

Preliminary Study of Clinical Antidiabetic Activity of Salam Leaves (Eugenia Polyantha) and Sambiloto Leaves (Andrographis Paniculata) In Type 2 Diabetic Patients

Diabetes mellitus is one of disease with high prevalence in the world. Salam (Eugenia polyantha) and Sambiloto (Andrographis paniculata) are plant that widely used traditionally for medicine including to treat diabetes mellitus. Many studies have revealed that these herbs have bioactive compounds that contribute to antidiabetic properties. The objective of the present study is to analyze the clinical antidiabetic properties of Eugenia polyantha and Andrographis paniculata leaves in type 2 diabetic patients. Clinical test with before and after design was used as method. Sample was designed by consecutive sampling with inclusion and exclusion consideration. Total subject of this study are 40 peoples and were divided into two group. One group consumed Eugenia polyantha leaf and the other one consumed Andrographis paniculata leaf. 300 mg of these medicinal plants was given as capsule. The prescription was 1-2 capsule per day for one week. During this study we observed several parameters include: patients characteristic, blood glucose level, uric acid, total cholesterol, blood pressure and other subjective complaints. The result showed that among 20 respondents of each group, there are 70% and 80% respondents decreased fasting blood glucose level (<140 mg/dL) compared to before treatment with these herbs. It can be concluded that Andrographis paniculata and Eugenia polyantha leaf may have positive role in type 2 diabetic patients.

Protective effects of quercetin and crocin in the kidneys and liver of obese Sprague-Dawley rats with Type 2 diabetes: Effects of quercetin and crocin on T2DM rats.

Quercetin and crocin are the main active constituents of Eucommia and Gardenia species, respectively. This study was conducted to explore the effects of quercetin and crocin on fat reduction and renal fibrosis and the relationship of these compounds with autophagy. First, a model of high-fat diet- and streptozotocin-induced type 2 diabetes was established and then subjected model animals to 8 weeks of metformin, quercetin and crocin gavage. Then, a high glucose-induced rat mesangial cells (RMCs) model was established, and these cells were cocultured with quercetin and crocin. The results showed that quercetin and crocin can decrease fasting blood glucose levels, reduce fat accumulation in the liver, alleviate renal fibrosis, and reduce blood lipid levels. Quercetin and crocin increased autophagy-related protein (LC3, Atg5, Beclin-1 and p-AMPK) levels in the liver and decreased autophagy-related protein (LC3, Atg5, Beclin-1 and p-AMPK) levels in the kidneys. Moreover, quercetin and crocin inhibited the excessive proliferation of RMCs induced by high-glucose (HG) conditions, decreased autophagy-related protein (LC3, Atg5, Beclin-1 and p-AMPK) levels, and decreased TGF-β1 expression. Importantly, cotreatment with quercetin and crocin had a more significant effect than treatment with either compound alone. These results suggest that combined administration of quercetin and crocin can more significantly reduce blood glucose/lipid levels and improve renal fibrosis than administration of either compound alone and that AMPK-dependent autophagy might be involved in this process. Eucommia ulmoides Oliv. and Gardenia could be developed as drugs for Type 2 diabetes treatment.

APX-115, a pan-NADPH oxidase inhibitor, protects development of diabetic nephropathy in podocyte specific NOX5 transgenic mice

NADPH oxidases (NOXs) are comprised of different isoforms, NOX1 to 5 and Duox1 and 2, and they trigger diabetic nephropathy (DN) in the patients with diabetes mellitus. Recently, it was shown that, compared to the other isoforms, the expression of NOX5 was increased in the patients with DN and, NOX5 has been suggested to be important in the development of therapeutic agents. The effect of pan-NOX inhibition by APX-115 has also been investigated in type 2 diabetic mice.However, since NOX5 is absent in mice, we evaluated the effect of pan-NOX inhibition by APX-115 in Nox5 transgenic mouse. Wild type and renal podocyte specific NOX5 transgenic mice (NOX5 pod+) were fed with high-fat diet (60% kcal fat) and treated with APX-115 (60 mg/kg) by oral gavage for 14 weeks.APX-115 significantly improved pancreatic beta cell function by decreased fasting blood glucose levels and increased insulin levels. Further, the total serum cholesterol, triglycerides, and urinary albumin/creatinine levels were also significantly decreased by APX-115 treatment. Increased NOX5 mRNA expressions, increased desmin levels, and reduced podocin protein expressions in the kidney of NOX5 pod + mice were also significantly restored to normal levels by APX-115 treatment. Moreover, APX-115 inhibited the expression of inflammation-related proteins such as TRAF6.Collectively, these data suggest that APX-115 might be a promising therapeutic agent for the treatment of DN because of its pan-NOX inhibitory activity, including its NOX5 inhibitory activity, and also owing to its anti-inflammatory effect.

Antidiabetic and antihyperlipidemic effects of Argyreia pierreana and Matelea denticulata: Higher activity of the micellar nanoformulation over the crude extract

Background and aimHerbal medicine combined with nanotechnology is widely proposed to improve the oral bioavailability, reduce the required dose and side effects, and improve the pharmacological efficacy of extracts. Thus, this study evaluated the in vivo antidiabetic and antihyperlipidemic activities of ethanolic leaf extracts of Argyreia pierreana (AP) and Matelea denticulata (MP) plants in comparison with their micellar nanoformulations. Materials and methodsThe mixed micelles (MMs) loaded with crude extracts (CEs) of AP and MD (AP-MMs and MD-MMs) were prepared using a film dispersion technique. Type 2 diabetes was induced in rats using high-fat diet (HFD) and low-dose (35 mg/kg) streptozotocin (STZ) injection. The pharmacological actions of CEs, AP-MMs and MD-MMs were determined in type 2 diabetic Sprague-Dawley rats. ResultsOral treatments with low-dose AP-MMs and MD-MMs having a mean particle size of 163 ± 10 nm and 145 ± 8 nm respectively, resulted in significantly decreased fasting blood glucose level and increased serum insulin, glucokinase levels, and normalized the elevated levels of hemoglobin A1C and glucose-6-phosphatase. Both extracts significantly decreased serum total cholesterol, triglycerides, and low-density lipoprotein, as well as elevated high-density lipoprotein levels. Additionally, improvements in antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and malondialdehyde levels were evidenced clearly in tested vital organs (brain, heart, liver). ConclusionThis is the first report of the antidiabetic and antihyperlipidemic activities of ethanolic leaf extracts of AP and MP plants. Our findings indicate the potential utility of nanotechnology in improving the oral therapeutic efficacy of herbal extracts.

Differential expression of glycoprotein IV on monocyte subsets following high-fat diet feeding and the impact of short-term low-dose aspirin treatment

ObjectiveTo assess the levels of glycoprotein GPIV (CD36) expression on peripheral blood monocyte subsets, in a mouse model of glucose intolerance. Moreover, to determine the effect of; low-dose aspirin (LDA) alone, LDA combined with metformin, or clopidogrel alone, on the expression of CD36 on subsets of circulating monocytes. MethodThe study consisted of two experimental phases. In experiment one, the mice (n = 14) were randomised to receive a low-fat diet (LFD) or a high-fat diet (HFD) for eight weeks. Whereas the secondary phase of the experiment, comprised of twenty-four HFD-fed mice treated with LDA alone (3 mg/kg), or in combination with metformin (150 mg/kg), or clopidogrel alone (10 mg/kg) for six weeks. The surface expression of CD36 on monocytes was measured using flow cytometry. ResultThe levels of CD36 expression on monocytes were upregulated in the HFD-fed compared to LFD-fed group (p < 0.05). In addition, HFD group showed; no significant changes in body weight (p = 0.3848), however, blood glucose (p = 0.0002) and insulin (p = 0.0360) levels were markedly increased following HFD-feeding. Interestingly, all treatments reduced the expression of CD36 on monocytes, decreased fasting blood glucose levels (p = 0.0024) and increased circulating monocyte levels (p = 0.0217) when compared to the untreated HFD group. Moreover, treatment with LDA alone increased basophils levels (p = 0.0272), while when combined with metformin showed an improved effect in enhancing eosinophil levels (p = 0.0302). ConclusionHFD-feeding increased the expression of CD36 on monocyte subsets. LDA as a monotherapy or combined with metformin was as effective as clopidogrel monotherapy, in downregulating the expression of CD36 on monocyte subsets. These treatments may be of relevance in preventing cardiovascular complications associated with impaired glucose tolerance.

Glucagon receptor antagonism promotes the production of gut proglucagon-derived peptides in diabetic mice

Glucagon is an essential regulator of glucose homeostasis, particularly in type 2 diabetes (T2D). Blocking the glucagon receptor (GCGR) in diabetic animals and humans has been shown to alleviate hyperglycemia and increase circulating glucagon-like peptide-1 (GLP-1) levels. However, the origin of the upregulated GLP-1 remains to be clarified. Here, we administered high-fat diet + streptozotocin-induced T2D mice and diabetic db/db mice with REMD 2.59, a fully competitive antagonistic human GCGR monoclonal antibody (mAb) for 12 weeks. GCGR mAb treatment decreased fasting blood glucose levels and increased plasma GLP-1 levels in the T2D mice. In addition, GCGR mAb upregulated preproglucagon gene expression and the contents of gut proglucagon-derived peptides, particularly GLP-1, in the small intestine and colon. Notably, T2D mice treated with GCGR mAb displayed a higher L-cell density in the small intestine and colon, which was associated with increased numbers of LK-cells coexpressing GLP-1 and glucose-dependent insulinotropic polypeptide and reduced L-cell apoptosis. Furthermore, GCGR mAb treatment upregulated GLP-1 production in the pancreas, which was detected at lower levels than in the intestine. Collectively, these results suggest that GCGR mAb can increase intestinal GLP-1 production and L-cell number by enhancing LK-cell expansion and inhibiting L-cell apoptosis in T2D.