Decreased Fasting Blood Glucose Research Articles

Effects of a ready-to-eat cereal formula powder on glucose metabolism, inflammation, and gut microbiota in diabetic db/db mice.

The cereal formula powder, Zhengda Jingshan (ZDJS), comprises dietary fiber, multivitamins, fine protein, and various cereal ingredients. The present study evaluated the effects of ZDJS on glucose metabolism and explored the corresponding mechanisms in terms of modulating gut microbiota and the fecal metabolome. Type 2 diabetic db/db mice were given ZDJS (1 g/kg) orally twice daily for 55 days, after which glucose metabolism, inflammation, gut microbiota, and fecal metabolomics were assayed. Repeated administration of ZDJS was associated with a trend toward decreasing fasting blood glucose and a 0.12% decrease in hemoglobin A1c (HbA1c), as well as statistically significant increases in the insulin sensitivity index and decreases in serum levels of tumor necrosis factor (TNF‐α) and ileum expression of mucin‐2. ZDJS also ameliorated the compensatory enlargement of islets and decreased the ratio of the α‐cell area to total islet area; however, this amelioration of impaired oral glucose tolerance became less pronounced as treatment continued. In addition, ZDJS remarkably decreased the abundance of phylum Proteobacteria and the phylum ratio of Firmicutes to Bacteroidetes, as well as altered the fecal metabolic profile. Taken together, our findings demonstrate that ZDJS improved glucose metabolism and reduced inflammation in type 2 diabetic db/db mice, which may be associated with a reshaping of the gut microbiome and fecal metabolome in db/db mice. Thus, our study suggests that ZDJS may represent a complementary therapy for patients with type 2 diabetes.

Anti-diabetic and lipid-lowering effects of drimane sesquiterpenoids isolated from Zygogynum pancheri

Recently, it has been shown that drimane-type sesquiterpenoids isolated from Zygogynum pancheri, a species native to New Caledonia, possessed significant α-amylase inhibitory activities. To further explore their antidiabetic potential, we investigated the effect of 1β-O-(E-cinnamoyl)-6α-hydroxy-9epi-polygodial (D) and 1β-E-O-p-methoxycinnamoyl-bemadienolide (L), two of the most active compounds of the series, on diabetic model rats. Compounds D and L (2 mg kg/day) were daily and orally administrated for 30 days to streptozotocin (STZ) (150 mg/kg) induced male diabetic Wistar rats. Animals were allocated into five groups of six rats. Comparatively to diabetic rats, treatments with D and L compounds were able to significantly (P < 0.05) decrease Fasting Blood Glucose (FBG) (70.15%, 71.02%), serum total cholesterol (46.27% and 39.38%), triglycerides (56.60% and 58.15%), creatinine (37.31% and 36.49%) and uric acid levels (67.76% and 69.68%), respectively. Compounds D and L also restored the altered plasma enzyme (aspartate aminotransferase, AST (47.83% and 43.20%), alanine aminotransferase, ALT (49.76% and 48.35%, alkaline phosphatase, ALP (72.78% and 73.21%)) and lactate dehydrogenase, LDH (47.95% and 53.93%) levels to near normal, respectively. Administration of Glymepiride, significantly (p < 0.05) reduced FBG (73.94%) in STZ induced diabetic rats. Additionally, the compounds D and L exhibited inhibitory effects in vivo on lipase activity of diabetic rats (54.83% and 52.25%), respectively. The outcomes of this study suggested that these two drimanes could be considered as efficient hypoglycemic, hypolipidemic and antiobesity agents for diabetes management and its complications.

Angiotensin converting enzyme inhibitor potentiates the hypoglycaemic effect of NG-nitro-L-arginine methyl ester (L-NAME) in rats

The inhibition of renin angiotensin system pathway has been largely documented to be effective in the control of cardiovascular events. The present study investigated the effect of angiotensin converting enzyme (ACE) inhibitor on fasting blood glucose level in hypertension induced by the inhibition of nitric oxide synthase (NOS) in male Wistar rats. Hypertension was induced by the inhibition of NOS using a non-selective NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). The blockade of NOS resulted in an increase in blood pressure, ACE, angiotensin II and endothelin-1 levels, and a decrease in fasting blood glucose and nitric oxide (NO) levels. The hypertensive rats treated with ACE inhibitor (ramipril) recorded a decrease in blood pressure, ACE, angiotensin II, endothelin-1, NO and fasting blood glucose levels, and an increase in prostacyclin level. In conclusion, ACE inhibitor potentiated the hypoglycaemic effect of NOS inhibitor and this effect is independent of NO and pancreatic insulin release.

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.

Efektivitas Ekstrak Teh Hijau (Camellia sinensis L.) terhadap Penurunan Kadar Glukosa Darah Puasa Tikus Wistar (Rattus norvegicus) yang diInduksi Aloksan

The sufferers of Diabetes Mellitus (DM) in Indonesia is the highest with fourth number in the world, with a mortality rate of 1.2 million in 2012. Because of it, DM research using antihyperglycemic green tea is needed. This study aims to determine the effectiveness of green tea extracts on decreasing fasting blood glucose (KGDP) levels in alloxan-induced white male Wistar rats. Samples were 30 male rats, aged 8-12 weeks, weight ± 200 grams. Rats were grouped into 6 groups with the first group (K1) as a control, the second group (K2) induced alloxan, the third group (K3) induced alloxan with glibenclamide, the fourth group (K4), the fifth group (K5), and the sixth group (K6) induced alloxan with green tea extract as the treatment with dose of green tea extract, 200 mg/kg, 400 mg/kg, and 800 mg/kg. The first, FBG level examination is done 3 days after induction of alloxan using a glucometer. Giving green tea extract was given for 16 days orally, then FBG level re-examined from the tail of rats. One Way ANOVA Test Results, there is the effectiveness of green tea extract on reducing FBG level (p = 0,000). The post hoc Bonferroni test showed that giving 800 mg/kg of green tea extract was the best dose in reducing KGDP close to normal (p = 0,000).

PROTECTIVE ROLE OF BERBERINE IN AMELIORATING DIABETIC COMPLICATIONS IN STREPTOZOTOCIN-HIGH FAT DIET MODEL IN EXPERIMENTAL ANIMALS

Objective: Diabetes mellitus is a serious, complex metabolic disorder and growing health threat disease in the world. Berberine, one of the main constituent in Rhizoma coptidis is widely used in the treatment of diabetes. Potential of berberine in the management of diabetic complications, namely diabetic nephropathy and cardiomyopathy, is however, not yet explored. The present study was, therefore, undertaken to explore the potential of berberine for the management of diabetic nephropathy and diabetic cardiomyopathy in high-fat diet (HFD) and low dose streptozotocin (STZ) induced diabetes in rats.&#x0D; Methods: Rats were fed a high-fat diet for 4 w followed by a single intraperitoneal dose of streptozotocin (35 mg/kg). Animals were divided in five groups. Berberine was given orally in two different dose levels (75 mg/kg and 150 mg/kg) for 28 d. Metformin (100 mg/kg) was used as a standard antidiabetic drug. At the end of the study, parameters evaluated includes glycemic profile, lipid profile, left ventricular indices, urinary protein, serum creatinine, blood urea nitrogen and cardiac antioxidants. Histopathology of kidney and pancreas was carried out.&#x0D; Results: Berberine treated groups showed a significant decrease in fasting blood glucose, glycosylated Hb, creatinine, blood urea nitrogen and urinary total proteins, whereas there was a significant improvement in serum insulin, liver glycogen, skeletal muscle glycogen and cardiac antioxidant enzymes.&#x0D; Conclusion: Present study indicated that berberine shows a protective role in diabetes-associated renal and cardiovascular complications.

Effect of Moderate Treadmill Exercise on Hepatic Lipid Metabolism in Rats

Several and complex factors cause accumulation of large amounts of body fat as well as a disparity between energy intake and output. Generally, any increase in bodyweight can be attributed to the elevation in daily food intake and the reduction in energy expenditure. Several functions could be achieved by moderate exercise including maintaining an optimum body weight and muscle mass, lowering abdominal fat and increasing lipid catabolism. However, the exact molecular mechanisms involved remain understudied. Our study was designed mainly to evaluate the influence of moderate treadmill exercise on body metabolism with special reference to hepatic lipid metabolism. Twenty adult male Sprague Dawley rats weighting 200±20 gm were randomly assigned to either sedentary or exercised groups. The exercise protocol lasted for 20 mins/ 5 times / week along 4 weeks. Although no significant changes in body weight, insulin and corticosterone levels, there was a significant decrease in fasting blood glucose and serum leptin levels (81.06%and 75.49% respectively). The current exercise regime significantly increased serum high density lipoprotein (HDL-c) level (127.56%) and significantly decreased serum triacylglycerol (TAG), low density lipoprotein (LDL-c) and very low-density lipoprotein (VLDL-c) levels (75.50%, 62.83% and 74.48% respectively). Also, treadmill exercise significantly upregulated the hepatic expression of acetyl-CoA oxidase (ACO) and carnitine palmitoyl CoA transferase 1 (CPT1) (173% and 148% respectively) as well as significantly downregulated the hepatic acetyl-CoA carboxylase (ACC) (52%) but not fatty acid synthase (FAS) mRNA expression. Overall, these results suggest a beneficial effect of moderate treadmill exercise hepatic lipid metabolism.

1958-P: Neonatal Il-4 Induces a Persistent Decrease in Adipocyte Maturation

Adipose tissue is a central node for the dynamic regulation of systemic metabolism and energy expenditure. Little is known about adipogenesis in the newborn which is the critical window of adipose tissue development. Emerging data suggest that immune cells, particularly innate immune cells, play an important role in de novo beige adipogenesis and beige fat thermogenesis in mature rodents. In previous studies we showed that administration of low levels of IL-4 in the first week of life to rat pups results in decreased adiposity and improved glucose tolerance in adulthood, suggesting that beige adipogenesis may be enhanced by neonatal IL-4 administration. Developing animals produce higher levels of IL-4 compared to mature animals and use a distinct pre-adipocyte compartment for adipogenesis. In this study, we analyze the effects of IL-4 on adipogenesis in the developing rat. We demonstrate that a short and transient IL-4 exposure in the neonate during postnatal days 1-6 induces acute beige adipogenesis in the inguinal white adipose tissue (iWAT) that is associated with the upregulation of Ucp1 (n=6). Concurrently, adipocyte maturation is decreased with Adipoq downregulated (n=6). Pre-adipocytes from 10 week old mature rats that had been treated with IL-4 as neonates were differentiated in vitro and also show a decrease in Adipoq compared to controls (n=6). These data demonstrate that neonatal IL-4 induces a long term decrease in the maturation potential of pre-adipocytes. Interestingly, these adult differentiated pre-adipocytes show no change in Ucp1 expression after neonatal IL-4 exposure compared to control (n=6). Thus, neonatal IL-4 induces only acute beige adipogenesis, but impairs adipocyte maturation long term. Phenotypically, neonatal IL-4 resulted in decreased iWAT (n=7) and decreased fasting blood glucose in 10 week old animals (n=6) compared to control. Our studies show that the neonatal period is critical for adipocyte development and may influence the later onset of obesity. Disclosure T. Ying: None. P. Seale: None. R.A. Simmons: None. Funding National Institutes of Health (DK114054)

A Crossover Study of Freeze-Dried Strawberry Powder on Microvascular Function, Gut Microbiota, and Metabolic Phenotype in Overweight or Obese Postmenopausal Women

Abstract Objectives This study assessed the influence of short-term freeze-dried strawberry powder (FDSP) intake on gut microbial composition and select microbial-derived metabolites from feces, serum, and urine, and determine their relationship to microvascular function. Methods In this double-blind, controlled crossover study, postmenopausal overweight or obese women not taking any medications were randomly assigned to consume 39 g FDSP (equivalent to 3 servings fresh strawberries) or an isocaloric control powder mixed in water, daily for 4 weeks, separated by a 4-week washout period. Serum, urine, and fecal metabolomics were performed by proton Nuclear Magnetic Resonance (1H NMR) spectroscopy, microbiome analysis was performed by targeting the v4 region of the 16S rRNA gene. Microvascular function was evaluated as the Framingham reactive hyperemia index (fRHI). Additional measures included anthropometrics, fasting plasma lipids, glucose, and blood pressure. Results Overall, 19 women completed the protocol; with two additional women completing at least one arm of the study. After 4 weeks of FDSP intake, there was a trend toward improved fRHI compared to control (P = 0.069), and a decrease in fasting blood glucose when individuals were stratified according to cardiovascular disease risk (P = 0.049). Further, FDSP intake was associated with a significant increase in propane-1,2-diol, which was negatively correlated with fRHI, as well as the urinary metabolites 1-methylnicotinamide and hypoxanthine. Potential FDSP induced shifts in gut microbial composition will be presented. Conclusions This study confirms previous reports concerning the positive effects of FDSP intake on microvascular function and provides evidence that these changes may be driven in part by changes in metabolism. Funding Sources This work was funded by a grant awarded by the California Strawberry Commission and USDA-NIFA Hatch projects.

Ergosterol ameliorates renal inflammatory responses in mice model of diabetic nephropathy

Ergosterol (ERG) was reported to exhibit anti-inflammatory and anti-oxidative activities. Besides, ERG was found to attenuate kidney injury in the diabetic mouse. However, the protective effect of ERG in diabetic nephropathy-induced inflammation remains unclear. We aimed to study whether ERG could alleviate diabetic nephropathy-induced inflammation and explore the underlying mechanisms. The diabetic nephropathy mice model was induced by intraperitoneal injection of 30 mg/kg Streptozotocin (STZ). The inflammatory cytokines levels, and insulin concentration in the serum of both diabetic nephropathy patients and mouse model were determined by ELISA. mRNA and protein expression were analyzed by RT-PCR and Western blot, respectively. Fasting blood glucose levels were detected using a commercial kit. Blood biochemistry levels were determined by an automatic analyzer. Mesangium proliferation was detected by PAS staining. It was found that serum levels of IL-6, TNF-α, and MCP-1 dramatically increased in the diabetic nephropathy patients. In mice, ERG treatment greatly decreased fasting blood glucose levels, inflammatory cytokine levels, and renal injury, while it enhanced the insulin level. Mechanically, ERG treatment dramatically decreased NF-κB signaling pathway. Our findings highlight the potential of ERG as an effective agent to treat diabetic nephropathy.

Anti-diabetic effect of the polyphenol-rich extract from &lt;i&gt;Tadehagi triquetrum&lt;/i&gt; in diabetic mice

Purpose: To clarify the diabetes-reducing abilities of the polyphenol-rich extract from Tadehagi triquetrum (HC) in diabetic ob/ob mice.Methods: Aerial parts of T. triquetrum were extracted under reflux and partitioned by n-butanol to generate HC. The effects of HC consumption on blood glucose and lipids, insulin resistance, and liver glucose metabolism were evaluated in vivo. The main compounds of HC were tested for their effects on stimulating glucose consumption and uptake by HepG2 hepatocytes and C2C12 myotubes.Results: After HC treatment, body fat, subcutaneous fat, and epidydimal fat masses decreased (p &lt;0.05), while mean daily food intake was unaffected. HC (200–400 mg/kg) decreased fasting blood glucose, glycosylated serum protein (GSP), and glycosylated hemoglobin (HbAlc); it also lowered hyperinsulinemia, improved oral glucose tolerance, and reduced hyperlipidemia and liver fat content (p &lt; 0.05). HC treatment markedly elevated liver glycogen content and activity of hepatic glucokinase and pyruvate kinase (p &lt; 0.05). Eight polyphenols were isolated from HC, six of which potently stimulated glucose consumption and uptake in vivo.Conclusion: HC has potent antidiabetic activities. Polyphenols are the main compounds accounting for these effects. Chronic oral administration of HC may be an alternative therapy for managing diabetes, but this has to be subjected first to clinical studies.&#x0D; Keywords: Tadehagi triquetrum, Diabetes, Phenylpropanoid glucosides, Pyruvate kinase, Glucokinase

The Differences of TNF-α Levels and BMI in Diabetic Patients with Pulmonary Tuberculosis After Intensive Phase of Tuberculosis Treatment

Abstract. Introduction. Diabetes Melitus (DM) can cause complications, such as pulmonary tuberculosis (TB). Metabolic disorders are thought to be related to Tumor Necrosis Factor-α (TNF-α) metabolism, adipocytokines secreted by macrophages, which inhibit insulin transduction, has anti-mycobacterial activity, however, also negatively affect pathological TB process. This study aims to determine differences in TNF-α levels and Body Mass Index (BMI) in DM with pulmonary TB after intensive phase of antituberculosis treatment. Method. This prospective comparative analytical study with one-group pretest-posttest design, conducted during August 2019-September 2019 in outpatient of Type 2 DM with pulmonary TB at USU Hospital, Madani Medan Hospital, Teladan Health Center and Laboratory of Haji Adam Malik Medan after approval from the Health Research Ethics Commission. Data were analyzed after normality test, then mean difference and correlation test by using the SPPS program where p &lt;0.05 was considered significant. Results. This study showed an increase BMI, and decrease of fasting blood glucose, 2-hour post-prandial blood glucose, HbA1C and TNFα levels before and after intensive phase of antituberculosis treatment (p = 0,000; p = 0,000; p = 0,000; p = 0,000). Conclusion. There was a significant increase of BMI and decrease of TNFα level after intensive phase of antituberculosis treatment.

ApolipoproteinM overexpression through adeno-associated virus gene transfer improves insulin secretion and insulin sensitivity in Goto-Kakizaki rats.

Aims/ObjectiveThe development of type 2 diabetes is a result of insulin resistance in various tissues, including skeletal muscle and liver. Apolipoprotein M (ApoM) plays an important role in the function of high‐density lipoprotein, and also affects hepatic lipid and glucose metabolism. In this study, we aimed to investigate whether ApoM overexpression modulates glucose metabolism and improves insulin sensitivity.Materials and MethodsThe Goto‐Kakizaki (GK) rats were transfected with adeno‐associated virus (AAV) encoding rat ApoM gene or control blank. The oral glucose tolerance test (OGTT) and hyperinsulinemic‐euglycemic clamp (HEC) experiment were used to assess the insulin sensitivity of GK rats.ResultsThe results show that ApoM messenger ribonucleic acid and protein were significantly overexpressed in the pancreatic tissues. Overexpression of ApoM decreased fasting blood glucose and random blood glucose, improved glucose tolerance, and increased bodyweight and insulin levels in GK rats. The glucose infusion rate of rats in the AAV encoding rat ApoM gene group during HEC test was 1.04‐, 1.23‐ and 1.95‐fold higher than that in the AAV control blank group at 1–3 weeks after injection of AAV, respectively. A Wes‐ProteinSimple assay and quantification was carried out to assess phosphorylated protein kinase B/protein kinase B protein levels in the muscle tissues of ApoM‐overexpressing GK rats, and they were found to be higher than those of the control group at the seventh week after AAV injection.ConclusionsApoM overexpression through adeno‐associated virus gene transfer might improve insulin secretion and insulin sensitivity in GK rats.

Effect of exenatide, metformin and folic acid on experimentally induced metabolic–cognitive syndrome in rats

Background: Metabolic syndrome (MetS) and its relationship with cognitive impairment has been the subject of extensive research. Purpose: This study was designed to determine the effect of MetS on cognitive function, and the possibility of modulating this effect by exenatide, metformin and folic acid. Materials and Methods: 30 adult male albino rats were divided in 5 groups. Group (I): received a standard rat chow, group (II): none treated rats with MetS fed with 60% fructose added to the standard rat chow, group (III): rats with MetS treated with exenatide, group (IV): rats with MetS treated with metformin, group (V): rats with MetS treated with folic acid. At the end of the experiment, fasting blood glucose, fasting plasma insulin, HOMA-IR index, serum triglyceride, HDL-C, dopamine and BDNF levels in brain tissue were measured and cognitive performance was assessed by Morris water maze (MWM) test. Results: rats with MetS showed increased levels of fasting blood glucose, fasting plasma insulin, HOMA-IR index, arterial blood pressure, serum triglycerides, decreased HDL-C, dopamine and BDNF and showed memory impairment in MWM test. All treated groups resulted in decrease in fasting blood glucose, fasting plasma insulin, HOMA-IR index, arterial blood pressure, and serum triglycerides and increase in HDL-C, dopamine and BDNF as well as improvement in MWM test. Conclusion: MetS was associated with cognitive impairment. Exenatide, metformin and folic acid improved cognitive function in addition to improvement of metabolic parameters.

Changes in the biochemical, hematological and histopathological parameters in STZ-Induced diabetic rats and the ameliorative effect of Kigelia africana fruit extract

BackgroundBiochemical, hematological and histological changes are major observable clinical and pathological factors associated with Diabetes mellitus. Derangement in the levels of these parameters increases the risk of the development of complications. In another hand, gastrointestinal intolerance due to the development of lactic acidosis on the gastrointestinal tract and the intestinal microbiome is the toxic side effect of various synthetic antidiabetic agents. The use of Kigelia africana fruit extract for the treatment of diabetes has been scientifically validated. This study therefore aimed at investigating changes in the biochemical, hematological and histological parameters as well as the determination of the functional groups present in the hexane fraction of the fruit. MethodsThe fruits were extracted with ethanol and partitioned with n-hexane to obtain the hexane fraction. Diabetic rats induced with streptozotocin (STZ) were divided into 5 groups of 5 animals each and treated with 100, 200 and 400 mg/kg body weight (BW) hexane fraction alongside reference standard; glibenclamide. Fasting blood glucose levels and their body weights were monitored weekly. Animals were sacrificed at the end of 28-day treatment. Blood, liver, and kidney were collected for biochemical, hematological and histopathological analyses. Fourier transform infrared resonance (FTIR) spectroscopic analysis was carried out on the hexane fraction for functional group determination. ResultsThe hexane fraction of K. africana fruit extract decreased fasting blood glucose (FBG) levels significantly with ameliorative effects on the hematological parameters such as packed cell volume (PCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red blood cells (RBC) etc. There were significant regenerative differences in the biochemical activities as well as the renal cortex and midzone sections of the rat's kidney and liver when compared with untreated diabetic rats. The presence of polyphenolic functional groups via FTIR analysis suggested high antioxidant activities of the fruit extract. ConclusionThe use of Kigelia africana fruit extracts protects against biochemical, hematological and histological changes that are injurious to diabetic patients. Therefore, Kigelia africana fruit is a good hepatic- and nephroprotective agent and has a hemato-protective ability.

Molecular hydrogen improves type 2 diabetes through inhibiting oxidative stress.

The aim of the present study was to investigate the potential therapeutic effects of molecular hydrogen on type 2 diabetes mellitus (T2DM) in rats. Following maintenance on a high-fat diet for 4 weeks, a T2DM model was established using an injection of 30 mg/kg streptozotocin via the caudal vein into Sprague-Dawley rats. On day 0 and Day 80, the blood samples were obtained from each rat for the measurement of biochemical indicators including blood lipids, fasting blood glucose, hepatic glycogen, fasting serum insulin, insulin sensitivity index, insulin resistance index, serum superoxide dismutase (SOD) and serum malondialdehyde (MDA) using an automatic biochemical analyzer. The kidneys and pancreas tissues were harvested for HE staining and Western blot assay of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated (p)-p65, p65, p-IκB and IκB. The results showed that in rats with T2DM, molecular hydrogen treatment decreased fasting blood glucose levels, increased hepatic glycogen synthesis and improved insulin sensitivity. Treatment with molecular hydrogen also increased the production of SOD whilst decreasing the production of MDA. In addition, molecular hydrogen alleviated the pathological changes exhibited by pancreatic islets and kidney during T2DM. Mechanistically, molecular hydrogen decreased TLR4 and MyD88 expression levels whilst also decreasing p65 and NF-κB inhibitor phosphorylation. In conclusion, molecular hydrogen exerted therapeutic effects against T2DM by improving hyperglycemia and inhibiting oxidative stress through mechanisms that are associated with the TLR4/MyD88/NF-κB signaling pathway.

Safety evaluation and antihyperglycaemic effect of root extract of Maerua decumbens (Brongn.) DeWolf in Wistar rats

Local communities living in rural regions of Kenya use the plant, Maerua decumbens (Brongn.) DeWolf for various purposes including water purification (roots), as food (roots and fruits) and medicinal (various parts of the plant) for treatment of several ailments including diabetes mellitus. However, there is no scientific evidence on the safety and antidiabetic claims of Maerua decumbens roots despite its continued use. Therefore, this study aimed at evaluating oral acute and sub-acute toxicity of methanolic root extract of Maerua decumbens (400 and 800 mg/kg.b.w/day) in Wistar rats and also the antihyperglycaemic activity of the orally-administered extract in streptozotocin (STZ) induced diabetic rats. Phytochemicals were qualitatively analysed using standard procedures while the fingerprint chromatograph of the extract was revealed by high performance liquid chromatography (HPLC). Diabetes was induced in the experimental groups by single intraperitoneal injection of STZ at 50 mg/kg.b.w. Animal grouping was then done as follows; Groups 1: Normal control; 2: Normal on extract (400 mg/kg.b.w/day) 3; diabetic untreated control; 4, 5 & 6; diabetic treated with 100 and 400 mg/kg.b.w/day of root extract and metformin at 100 mg/kg.b.w/day, respectively. Effects of extract on fasting blood glucose (FBG) and body weights were monitored weekly in the 21 days anti-diabetic study. Also, liver malondialdehyde (MDA) levels were determined at the end of the treatment. For sub-acute toxicity studies, the extract did not affect organ weights of liver, kidney, heart and spleen and there were no pathological changes in the liver and kidney. Also, the blood biochemical and haematological parameters did not show any changes in all dosages although there were significant alterations in red blood cell’ indices but the values were within the published normal reference ranges for the species. Thus the extract was found to be relatively safe after oral sub-acute treatment in rats. On the other hand, the phytochemical-rich extract as also exhibited by the UV spectra of the compounds on diabetic rats showed a marginal increase in body weight, significant decreases in FBG and liver MDA levels versus untreated diabetic rats (p < 0.05). Therefore, Maerua decumbens root extract has great potential for use as a safe alternative medicine for the management of diabetes mellitus due to its antihyperglycaemic effects and reduction in hepatic lipid peroxidation.

Prospect of Sodium-Glucose Co-transporter 2 Inhibitors Combined With Insulin for the Treatment of Type 2 Diabetes.

Sodium–glucose co-transporter 2 (SGLT2) inhibitors are a new family of antidiabetic drugs that reduce blood glucose independent of insulin. In this review, we present the advantages and adverse effects of SGLT2 inhibitors plus insulin therapy as a treatment regimen for patients with type 2 diabetes (T2D). Compared with placebo, SGLT2 inhibitors plus insulin therapy could significantly decrease fasting blood glucose and HbA1c, thereby reducing the daily required dose of insulin. A reduction in body weight and improvements in insulin resistance and β-cell function have also been widely reported with this therapy, and other potential advantages, including the reduction in blood pressure, adverse cardiovascular outcomes, and visceral adipose tissue volume, have been revealed. SGLT2 inhibitors cause a greater reduction than dipeptidyl peptidase-4 (DPP-4) inhibitors in body weight and the risk of cardiovascular disease. Furthermore, compared with glucagon-like peptide-1 (GLP-1) agonists, SGLT2 inhibitors reduce blood pressure, and heart failure. As this therapy is an oral preparation, an improvement in patient compliance is also achieved. Despite these advantages, however, combination therapy with SGLT2 inhibitors and insulin has several risks. Although no difference has been found in the incidence of hypoglycemic events and urinary tract infection between the administration of this combination and that of placebo, the risk of genital tract infections was reported to increase with the combination therapy. Additionally, bone adverse effects, euglycemic diabetic ketoacidosis, and volume depletion—and osmotic diuresis—related adverse effects have been observed. Altogether, we could conclude that SGLT2 inhibitors plus insulin therapy is an efficient treatment option for patients with T2D, especially those requiring high daily insulin doses and those with insulin resistance, obesity, and a high risk of cardiovascular events. However, careful monitoring of the adverse effects of this combination is also warranted.

Effects of Metformin and Sitagliptin Monotherapy on Expression of Intestinal and Renal Sweet Taste Receptors and Glucose Transporters in a Rat Model of Type 2 Diabetes

Disordered intestinal sweet taste receptors (STRs) are implicated in glucose homeostasis by involving in incretin secretion and glucose absorption. However, the effects of antidiabetic medications on STRs, downstream molecules, and glucose transporters expression are unknown. In our study, ZDF rats (n=24) were randomly treated by metformin (MET, 215.15 mg/kg), sitagliptin (SIT, 10.76 mg/kg), or saline for 4 weeks. Fasting blood glucose and insulin levels were measured, and HOMA-IR and QUICKI index were calculated. One week later, we detected relative mRNA expression of T1R2/T1R3, α-gustducin, TRPM5 and glucose transporters including SGLT1, SGLT2, and GLUT2 in the small intestine and kidney. We found that though both metformin and sitagliptin effectively decreased fasting blood glucose, only metformin improved HOMA-IR and QUICKI (p<0.05). MRNA levels of STRs and sweet taste molecules in duodenum and jejunum were not different among three groups, but those in ileum were dramatically upregulated after SIT (vs. MET p<0.05; vs. CON p<0.01). SGLT1 and GLUT2 in ileum were markedly increased after SIT (p<0.01). In the kidney, expression of SGLT2 and GLUT2 were downregulated in both SIT and MET group (p<0.05). In conclusion, metformin and sitagliptin exerted different effects on expression of STRs and glucose transporters in the gut and kidney. STRs, downstream molecules, and glucose transporters in distal small intestinal were sensitively increased in response to sitagliptin than metformin treatment. Renal glucose transporters were downregulated after metformin and sitagliptin treatment.

Nutraceutical Improves Glycemic Control, Insulin Sensitivity, and Oxidative Stress in Hyperglycemic Subjects: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

The aim of this research was to investigate the effects of nutraceuticals including bitter melon, fenugreek, cinnamon, alpha-lipoic acid, zinc, biotin, chromium, and cholecalciferol on glycemic control, insulin sensitivity, lipid profiles, oxidative stress, and inflammatory markers in hyperglycemia. The study design was a randomized, double-blind, placebo-controlled trial. Subjects with hyperglycemia were randomly divided into 2 groups. The treatment group ( n = 52) was given a nutraceutical and the control group ( n = 50) was provided with a placebo for 12 weeks. Fasting blood glucose (FBG), hemoglobin A1c (HbA1C), homeostatic model assessment of insulin resistance (HOMA-IR), lipid profiles, biomarkers of oxidative stress, and inflammation were assessed before and after the intervention at 6 weeks and 12 weeks. Nutraceutical supplementation demonstrated a statistically significant decrease in FBG (13.4% and 18.9%), HbA1C (6.5% and 11.3%), and HOMA-IR (28.9% and 35.2%) compared with the placebo. Moreover, low-density lipoprotein-cholesterol (LDL-C) level was significantly reduced in the nutraceutical group (7.1% and 9.3%). Furthermore, the nutraceutical significantly decreased oxidative stress markers, oxidized LDL-C (14.8% and 18.9%) and malondialdehyde (16.6% and 26.2%) compared with the placebo. In conclusion, this nutraceutical can improve glycemic control, insulin resistance, lipid profiles, and oxidative stress markers in hyperglycemic subjects. Therefore, it has the potential to decrease cardiovascular disease risk factors. Clinical trial registration: TCTR20180907001, www.clinicaltrials.in.th.