Reduced Blood Glucose Concentrations Research Articles

Drug Promising Effect for Diabetic Mice of CARICA PAPAYA Leaves

Diabetics Mellitus is a major problem for city people worldwide. The objective of this study is finding the anti-diabetic and anti-hyper lipidaemic activity by using Carica papaya leaves. This leaves are not generally eaten but this leaves were eaten during dengue fever. The leaves extract is used for the treatment of diabetes and cancer. This leaves were collected from different place of Bangladesh and made methanolic extract then this extract was feed four groups of mice. The results showed that there was a significant (p<0.001 to p<0.05) reduction in blood glucose concentration (mmol/L) by the methanolic extract of C. papaya leaves at dose 100 mg/kg, 200 mg/kg and glibenclamide (used as standard) 5mg/kg body weight. C. papaya leaves extract also regulated the serum lipid profile levels significantly (p<0.001) at same dose in experimental model of diabetes mellitus. The level of serum SGPT, SGOT and CRP were also seen change to the normal level notably (p<0.001) by the oral administration of methanolic extract of C. papaya leaves. In conclusion this research finding indicate that the methanolic extract of Carica papaya leaves contains bioactive substances with hypoglycemic potency.

In vitro and in vivo postprandial hypoglycemic effects and comprehensive metabolite profiling of Dangjo chili pepper (Capsicum annuum L. cv. Dangjo)

The Dangjo chili pepper (DJ) has been reported to contain various compounds with α-glucosidase inhibitory activity. However, the hypoglycemic effect of DJ and the active ingredients responsible have not been fully investigated. Herein, the current study aimed to examine DJ as a novel α-glucosidase inhibitor for the prevention of hyperglycemia. The identification of metabolites and the assessment of α-glucosidase inhibitory activity was conducted in three chili pepper species. Glucose uptake inhibition by DJ ethanol extract (DJE) was evaluated in Caco-2 cells. Furthermore, an oral carbohydrate tolerance test was performed in C57BL/6 mice. A total of 18 metabolites were identified in Dangjo, Green, and Cucumber chili peppers. Among these, quercitrin was one the most abundant flavonoid in DJ. The DJ showed the highest inhibition of α-glucosidase activity against both maltose and sucrose compared to other peppers. In addition, isoorientin, quercitrin, and DJE had similar inhibitory activities for both substrates. Glucose uptake was significantly inhibited in the DJE group compared to the control group. The mice were orally administered freeze-dried DJ at 150 and 300 mg/kg body weight (B.W.), and blood glucose levels were measured. Under glucose loading, both groups had significantly reduced blood glucose concentration compared to the control group (p = 0.001). Under maltose loading, the blood glucose concentration was decreased in the 150 mg/kg B.W. group compared to the control group (p = 0.025). These results indicate that Dangjo chili pepper has the potential to function as a postprandial hypoglycemic agent by inhibiting the α-glucosidase activity.

Hypericum perforatum L. extract exerts insulinotropic effects and inhibits gluconeogenesis in diabetic rats by regulating AMPK expression and PKCε concentration

Ethnopharmacological relevanceHypericum perforatum L., commonly known as St. John's Wort (SJW), represents one of the best-known and most thoroughly researched medicinal plant species. The ethnobotanical usage and bioactivities related to H. perforatum include treatment of skin diseases, wounds and burns, gastrointestinal problems, urogenital diseases and psychiatric disorders, particularly depression. In the last decade, many studies focused on the bioactive constituents responsible for the antihyperglycemic and antidiabetic activity of SJW extracts. However, the mechanism by which H. perforatum extract exhibits these properties is still unclear. Hence, the current study was designed to gain insight into the underlying biochemical and molecular mechanisms by which wildly growing H. perforatum exerts its antihyperglycemic and antidiabetic activities. Material and methodsPlant material of H. perforatum was harvested from a natural population in the Republic of North Macedonia during full flowering season. Methanol (80% v/v) was used to extract bioactive components from HH powder. The dissolved HH dry extract (in 0.3% CMC) was given daily as a single treatment (200 mg/kg bw) during 14 days both in healthy and streptozotocin-induced diabetic rats. As a positive control, we applied glibenclamide. The activity of key enzymes involved in carbohydrate methabolisam in the liver were assessed, along with substrate concentration, as well as AMPK mRNA levels, PKCε concentration, plasma insulin level and pancreatic PARP activity. ResultsCompared to diabetic rats, treatment of diabetic rats with HH extract resulted with decreased activity of hepatic enzymes glucose-6-phospatase and fructose-1,6-bisphosphatase, increased liver glycogen and glucose-6-phosphate content, which resulted with reduced blood glucose concentration up to normoglycaemia. Non-significant changes were observed in the activity of hexokinase, glycogen phosphorylase and glucose-6-phospahte dehydrogenase. HH-treatment also caused an increase in plasma insulin concentration and increase in pancreatic PARP activity. Finally, HH treatment of diabetic rats showed significant increase in AMPK expression and decrease of PKCε concentration. ConclusionWe present in vivo evidence that HH- extract exert insulinotropic effects and regulate endogenous glucose production mostly by suppressing liver gluconeogenesis. The HH-treatment did not effected glycogenolysys and glycolysis. Finally, we confirm the antihyperglycemic and antidiabetic effect of HH-extract and the mechanism of this effect involves amelioration of AMPK and PKCε changes in the liver.

Lactobacillus-fermented yogurt exerts hypoglycemic, hypocholesterolemic, and anti-inflammatory activities in STZ-induced diabetic Wistar rats

Hyperglycemia is a symptom of type 2 diabetes mellitus, a chronic metabolic disease characterized by elevated blood glucose concentrations. Antidiabetic drugs are common treatments for this metabolic disorder; however, they may have unpleasant side effects. This study hypothesized that probiotic fermented products could preserve nutritional value, maintain metabolic homeostasis, and attenuate the inflammatory response associated with diabetes while reducing side effects. Lactobacillus plantarum KU985438 and Lactobacillus rhamnosus KU985439 showed the lowest alfa-amylase enzyme (α-amylase) activity among 8 lactobacilli tested. These 2 strains were used to develop functional fermented milk products, and their antidiabetic efficacy was tested in induced diabetic Wistar rats. The treatment of diabetic rats with L. plantarum KU985438 or L. rhamnosus KU985439 fermented yogurt resulted in a considerable reduction in blood glucose concentrations (136.79% and 145.17%, respectively) and α-amylase concentrations (56.84% and 56.84%, respectively) compared with conventional treatments. Diabetes relief began after 4 days of yogurt consumption compared with drug-based treatment. Significant improvements in both liver and kidney enzyme concentrations were also observed, in addition to a significant increase in high-density lipoprotein cholesterol concentrations and improved lipid profiles. Inhibition in nuclear factor κB and an increase in Bcl-2 concentrations were also detected. Histopathological examination of both hepatic and pancreatic cells revealed the positive effects of the studied treatment compared with standard treatment. Therefore, the selected Lactobacilli, which has hypoglycemic potential, could be used to produce functional nutraceutical antidiabetic supplements.

Sodium alginate and galactooligosaccharides ameliorate metabolic disorders and alter the composition of the gut microbiota in mice with high-fat diet-induced obesity

We aimed to investigate the effects of sodium alginate (SA) and galactooligosaccharides (GOS) on the metabolism and gut microbiota of high-fat diet (HFD)-fed obese mice. GOS and SA delayed high-fat diet-induced obesity, reduced the epididymal fat and liver indices, and improved the circulating lipid profile. Low- and high-dose GOS reduced weight gain by 48.8 % and 35.3 %, and low- and high-dose SA reduced it by 37.7 % and 34.4 %, respectively. GOS and SA reduced blood glucose concentration, probably by increasing the expression of glucose transporter 4. GOS and SA increased the expression of tight junction proteins (ZO-1 and occludin), reduced the D-lactic acid (D-LA) and lipopolysaccharide concentrations, and reduced the expression of toll-like receptors, consistent with improved intestinal barrier function. GOS and SA also increased the abundance of Bacteroidota, Bifidobacterium, and Lactobacillus; and reduced that of Patescibacteria in the gut. The abundance of Parabacteroides positively correlated with the circulating low-density lipoprotein-cholesterol (LDL-C) concentration; that of Lactobacillus negatively correlated with LDL-C, D-LA, and tumor necrosis factor-α concentration; and that of Bifidobacterium positively correlated with high-density lipoprotein-cholesterol concentration, according to Spearman correlation analysis. In conclusion, SA and GOS ameliorate obesity and the associated metabolic disorders in mice, and also modulate their gut microbial composition.

Review of SGLT2i for the Treatment of Renal Complications: Experience in Patients with and Without T2D

The management of type 2 diabetes (T2D) involves decreasing plasma glucose levels and reducing cardiovascular and microvascular complications. Diabetic kidney disease (DKD), defined as presence of albuminuria, impaired glomerular filtration, or both, is an insidious microvascular complication of diabetes that generates a substantial personal and clinical burden. The progressive reduction in renal function and increased albuminuria results in an increase of cardiovascular events. Thus, patients with DKD require exhaustive control of the associated cardiovascular risk factors. People with diabetes and renal impairment have fewer options of antidiabetic drugs because of contraindications, adverse effects, or altered pharmacokinetics. Sodium–glucose cotransporter type 2 inhibitors (SGLT2i) reduce blood glucose concentrations by blocking the uptake of sodium and glucose in the proximal tubule and promoting glycosuria, and these agents now have an important role in the management of T2D. The results of several cardiovascular outcomes trials suggested that SGLT2i are associated with improvements in renal endpoints in addition to their reduction in cardiovascular events and mortality, which represents a major advance in the care of this population. The dedicated kidney outcomes trials have confirmed the renoprotective action of SGLT2i across different glomerular filtration and albuminuria values, even in patients with non-diabetic chronic kidney disease. Notably, this improvement in kidney function may indirectly benefit cardiac function through multifaceted interorgan cross talk, which can break the cardiorenal vicious circle linked to T2D. In this article, we briefly review the different mechanisms of action that may explain the renal beneficial effects of SGLT2i and disclose the results of the key renal outcome trials and the subsequent update of related clinical guidelines.

Trehalose Activates Hepatic and Myocardial Autophagy and Has Anti-Inflammatory Effects in db/db Diabetic Mice.

Db/db mice (carrying a mutation in the gene encoding leptin receptor) show autophagy suppression. Our aim was to evaluate the effect of autophagy inducer trehalose on liver and heart autophagy in db/db mice and to study inflammation dysregulation and the suitability of chitinases’ expression levels as diabetes markers. Thirty-eight male db/db mice and C57/BL mice (control) were used. The db/db model manifested inflammation symptoms: overexpression of TNF-α in the spleen and underexpression of IL-10 in the liver and spleen (cytokine imbalance). Simultaneously, we revealed decreased expression of chitotriosidase (CHIT1) and acid mammalian chitinase (CHIA) in the liver of db/db mice. CHIA expression in db/db mice is significantly lower only in the spleen. Trehalose treatment significantly reduced blood glucose concentration and glycated hemoglobin. Treatment of db/db mice by trehalose was followed by increased autophagy induction in the heart and liver (increased autolysosomes volume density studied by morphometric electron-microscopic method). Trehalose exerted beneficial cardiac effects possibly via increased lipophagy (uptake of lipid droplets). The autophagy activation by trehalose had several positive effects on the heart and liver of db/db mice; therefore, lipophagy activation seems to be a promising therapy for diabetes.

Hypoglycemic and hypolipidemic properties of Casuarina equisetifolia leaf extracts in alloxan induced diabetic rats

BackgroundCausarina equisetifolia is a plant used traditionally as a remedy for various disorders such as diabetes, hyperlipidemia, gastric problems and muscle weakness. The aqueous, ethanol and methanol extracts of C. equisetifolia leaves were studied for hypoglycemic and hypolipidemic potentials. MethodologyPhytochemical analysis was carried out using standard procedures. Rats of both sexes, weighing (145–255 g) were randomly allotted to six groups with each group having four rats. Rats in group A were the normoglycemic, while those in groups B, C, D, E, and F were rendered diabetic by the administration of 110 mg/kg bodyweight of alloxan monohydrate. Group C rats were treated with 15 mg/kg bodyweight of standard drug (Glidazide), while groups D, E, and F rats were respectively treated with 150 mg/kg bodyweight of aqueous, ethanol, and methanol extracts for 15 days. The group B rats were untreated (negative control). Blood glucose was checked after every three days using glucometer. At the end of the treatment, the rats were anaesthetized under chloroform vapor and blood samples were collected by jugular puncture and used for analyzing biochemical parameters. ResultsExtracts showed presence of tannins, flavonoids, saponins, phenols, alkaloids and reducing sugars. There was 64%, 59% and 58% reduction in blood glucose concentration of diabetic rats treated with ethanol, aqueous, methanol extracts respectively. Serum cholesterol and triacylglycerol of the three treated groups reduced (p < 0.05) with the aqueous and methanol extract treated groups having the most significant reductions in both variables (147.93±8.04, 152.91±10.85 mg/dL) when compared with the diabetic group (203.21±6.45, 355.16±11.25 mg/dL) respectively. AST and ALP activities reduced significantly (p < 0.05) in the aqueous extract treated group (33.18±4.48, 52.60±7.23 u/L) with no significant differences when values were compared to that of the normal control group (25.64±4.18, 44.13±5.80 u/L) respectively. Urea concentration decreased in all extract treatment groups except the group treated with the aqueous extract. Creatinine also decreased in the extract treated groups apart from the group treated with the aqueous and methanol extracts when both compared with the normal control group. ConclusionThe extracts from the leaves of C. equisetifolia have hypoglycemic and hypolipidemic effects, and can be further explored as a natural novel lead for drug development in the management of diabetes and dyslipidemia.

ASAM KLOROGENAT PADA KOPI DAN OBESITAS: A SYSTEMATIC REVIEW Chlorogenic Acid in Coffee and Obesity: A Systematic Review

Obesity are defined as excessive fat accumulation caused of imbalance energy in and energy out. Consuming a cup of coffee can help prevent obesity through chlorogenic acid compound. Chlorogenic acid is one of biactive component that has an important role to our body. Chlorogenic acid has a potential role in body weight reduction and preventing obesity. Chlorogenic acid has an effect to inhibit the absorption of glucose in the intestine, block the conversion of glucose to fat in the adipose tissue and protect from weight gain. Chlorogenic acid that contain in coffee has a differences that depend on variety, type, roasting duration, temperature and coffee bean size. Based on several studies, giving chlorogenic acid as a form of supplementation or green coffee extract has demonstrated a consistent result. Those studies explain that chlorogenic acid in coffee can inhibit body fat accumulation and reducing body weight. The aim of this systematical review was to know the contain of chlorogenic acid in coffee and analyze the effect of giving chlorogenic acid to obesity. The experimental studies in human and animal subjects in the last 15 years as inclusion criteria and studies that is not represent the anthropometry result as exclusion criteria through electronic database were comprehensively reviewed. The result from five studies demonstrated that chlorogenic acid has an effect to reduce body weight, reduce body fat percentage, and reduce blood glucose concentration with the duration and chlorogenic acid dosage differently. Chlorogenic acid has many benefits in improving the obesity.

Hydro-Alcoholic Root Extracts of Ziziphus abyssinica is Effective in Diabetes Nephropathy and Diabetic Wound Healing

Background: This study evaluated the potential of Ziziphus abysinnica root extract in managing hyperglycaemia in type 2 diabetes mellitus (T2DM), diabetic wound healing and diabetic nephropathy.&#x0D; Methodology: Blood glucose concentrations were measured daily for 14 days after daily administrations of either Ziziphus abysinnica (30, 100, and 300 mg/kg, p.o), metformin (300 mg/kg, p.o) or normal saline as negative control before diabetes induction using a single dose of Streptozotocin (60 mg/kg, i.p) and nicotinamide (120 mg/kg, i.p). Histopathological analysis was performed on the harvested kidneys following administration with Ziziphus abysinnica in diabetic rats. The diabetic wound healing potentials of the plant was also evaluated in streptozotocin-induced diabetic rats by treating them with 15%w/w ZAE ointment.&#x0D; Results: Generally, the percentage of blood glucose levels analysed following administration of drugs were found to be dose-dependent. The highest dose of ZAE (300 mg/kg) had a higher percentage reduction in blood glucose concentration when compared to metformin (300 mg/kg). The lowest dose (30 mg/kg) of ZAE administered attenuated STZ induced pathological damage and showed moderate to maximal improvement to the kidney nephrons. In contrast, the 100 mg/kg and 300 mg/kg dose ZAE demonstrated minimal pathological changes to the kidney architecture.&#x0D; Conclusion: Overall, our study demonstrated the antidiabetic potential of Ziziphus abysinnica, suggesting its possible therapeutic benefit in diabetic wound healing and diabetic nephropathy.

Implication of Mode of Consumption of Allium cepa L. (Onion) on Lipoglycemic and Anthropometric Impacts in Diabetic Rats: A Function of Choice

Background: Use of Allium cepa L. (Onion) as spice in traditional cooking, concoctions and preparations has long been established since ancient time. However, the implication of its mode of consumption on health benefits is inadequately considered or explored. Objectives: This experimentally-controlled designed nutritional study aimed to determine and compare the effects of consumption of Allium cepa in its raw form and in mixed meal on body weight, glycemic tolerance/control and, lipid profile in diabetic rats. Materials and Methods: Twenty one adult (170-200g) male Wistar rats were randomly categorized into three experimental groups (n=7, each): Diabetic Control (DC), Diabetic Onion Extract-Treated (DOE), and Diabetic Onion-supplemented Diet-Fed (DSO). Diabetes was inducted with 150 mg/dL, alloxan monohydrate solution intraperitoneally. Animals were fed according to the experimental design with water ad libitum for six weeks. Body weights and Fasting blood sugar (FBS) concentrations were measured twice weekly. LP and OGTT were conducted. Microsoft Excel and statistical SPSS program version 22 were used for data analysis. Results are expressed as mean ± SEM. Comparison between groups were made using Students’t-test and one way ANOVA. Results: Consumption of onion in its raw (aqueous extract) form caused more reduction in blood glucose concentration (DOE - 38.14% versus DSO - 11.2%; P = 0.02) and body weight gain (DOE -7.71% versus DSO - 16.32%; P = 0.01), with improved lipid profile than when ingested in mixed meal (supplemented diet). Glycemic response curves peaked at 60 minutes of glucose challenge in DSO and DOE groups. Conclusion: Mode of consumption of Allium cepa, influenced its therapeutic anthropometric and lipoglycemic effects in diabetic rats.

Characterization of Enlarged Kidneys and Their Potential for Inducing Diabetes in DEK Rats.

Simple SummaryThe worldwide prevalence of diabetes mellitus (DM) in 2020 has been estimated at 463 million patients. About 90% of patients with diabetes have type 2 diabetes mellitus (T2D), caused primarily by insulin resistance and insufficiency. However, the specific etiology of T2D remains unknown. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a novel class of anti-diabetic drugs that act independently of insulin and reduce blood glucose concentrations by inhibiting the reabsorption of glucose at renal proximal tubules. SGLT2 inhibitors have highlighted the role of the kidneys in glycemic control in diabetes. The kidneys have multiple roles in systemic glucose metabolism, such as glucose reabsorption, gluconeogenesis, and insulin degradation. Therefore, putative renal hyperfunction might contribute to the development of T2D. The present study characterized rats from a strain of novel type 2 diabetes model with enlarged kidneys (DEK). Their kidneys have increased parenchyma (nephrons and tubules), and uninephrectomy immediately after the onset inhibited the development of T2D for a significant period in DEK rats. These results highlight the contribution of kidney to the development of T2D, and indicate that the kidneys are therapeutic targets to prevent T2D.The kidneys participate in the regulation of systemic glucose metabolism via gluconeogenesis, insulin degradation, and the tubular reabsorption of glucose. The present study characterized rats from a strain of a novel type 2 diabetes model with enlarged kidneys (DEK). Histological and biochemical analyses of DEK rats were performed to assess the relationships between their kidneys and hyperglycemia. The kidney weight of diabetic DEK (DEK-DM) gradually increased over time from the onset of diabetes, with the glomerular number being higher in DEK-DM than in normal DEK (DEK-cont). A positive correlation between blood glucose level and kidney weight was observed in DEK-DM. The similar glomerular size and single glomerular creatinine clearance in DEK-cont and DEK-DM indicated that glomerular hypertrophy and hyperfiltration were not involved in the renal enlargement. Uninephrectomy (1/2Nx) in DEK-DM resulted in a reduction in blood glucose level at 7–28 post-operation days, with this concentration remaining lower than in Sham group until 84 days post-operation. 1/2Nx also improved systemic conditions, including reduced body weight gain, polyuria, polydipsia, and hyperphagia. Plasma concentrations of Na, total cholesterol, albumin, and total protein were higher, and urinary excretion of glucose, urea nitrogen, and proteins were lower, in the 1/2Nx than in the Sham group. Remnant kidney weight was two-fold higher in the 1/2Nx than in the Sham group 84 days later. In addition, 1/2Nx resulted in renal tubular dilatation but not in the progression of fibrosis or glomerular lesions. Taken together, these findings indicate that enlarged kidneys were associated with the onset of diabetes and with the resistance to diabetic nephropathy in DEK-DM.

Short Duration Alagebrium Chloride Therapy Prediabetes Does Not Inhibit Progression to Autoimmune Diabetes in an Experimental Model.

Mechanisms by which advanced glycation end products (AGEs) contribute to type 1 diabetes (T1D) pathogenesis are poorly understood. Since life-long pharmacotherapy with alagebrium chloride (ALT) slows progression to experimental T1D, we hypothesized that acute ALT therapy delivered prediabetes, may be effective. However, in female, non-obese diabetic (NODShiLt) mice, ALT administered prediabetes (day 50–100) did not protect against experimental T1D. ALT did not decrease circulating AGEs or their precursors. Despite this, pancreatic β-cell function was improved, and insulitis and pancreatic CD45.1+ cell infiltration was reduced. Lymphoid tissues were unaffected. ALT pre-treatment, prior to transfer of primed GC98 CD8+ T cell receptor transgenic T cells, reduced blood glucose concentrations and delayed diabetes, suggesting islet effects rather than immune modulation by ALT. Indeed, ALT did not reduce interferon-γ production by leukocytes from ovalbumin-pre-immunised NODShiLt mice and NODscid recipients given diabetogenic ALT treated NOD splenocytes were not protected against T1D. To elucidate β-cell effects, NOD-derived MIN6N8 β-cell major histocompatibility complex (MHC) Class Ia surface antigens were examined using immunopeptidomics. Overall, no major changes in the immunopeptidome were observed during the various treatments with all peptides exhibiting allele specific consensus binding motifs. As expected, longer MHC Class Ia peptides were captured bound to H-2Db than H-2Kb under all conditions. Moreover, more 10–12 mer peptides were isolated from H-2Db after AGE modified bovine serum albumin (AGE-BSA) treatment, compared with bovine serum albumin (BSA) or AGE-BSA+ALT treatment. Proteomics of MIN6N8 cells showed enrichment of processes associated with catabolism, the immune system, cell cycling and presynaptic endocytosis with AGE-BSA compared with BSA treatments. These data show that short-term ALT intervention, given prediabetes, does not arrest experimental T1D but transiently impacts β-cell function.

In Vitro & In Vivo Anti-Hyperglycemic Potential of Saponins Cake and Argan Oil from Argania spinosa.

The Argan tree (Argania spinosa. L) is an evergreen tree endemic of southwestern Morocco. For centuries, various formulations have been used to treat several illnesses including diabetes. However, scientific results supporting these actions are needed. Hence, Argan fruit products (i.e., cake byproducts (saponins extract) and hand pressed Argan oil) were tested for their in-vitro anti-hyperglycemic activity, using α-glucosidase and α-amylase assays. The in-vivo anti-hyperglycemic activity was evaluated in a model of alloxan-induced diabetic mice. The diabetic animals were orally administered 100 mg/kg body weight of aqueous saponins cake extract and 3 mL/kg of Argan oil, respectively, to evaluate the anti-hyperglycemic effect. The blood glucose concentration and body weight of the experimental animals were monitored for 30 days. The chemical properties and composition of the Argan oil were assessed including acidity, peroxides, K232, K270, fatty acids, sterols, tocopherols, total polyphenols, and phenolic compounds. The saponins cake extract produced a significant reduction in blood glucose concentration in diabetic mice, which was better than the Argan oil. This decrease was equivalent to that detected in mice treated with metformin after 2–4 weeks. Moreover, the saponins cake extract showed a strong inhibitory action on α-amylase and α-glucosidase, which is also higher than that of Argan oil.

Empagliflozin ameliorates symptoms of diabetes and renal tubular dysfunction in a rat model of diabetes with enlarged kidney (DEK).

BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used to reduce hyperglycemia. The present study investigated the effects of a SGLT2 inhibitor, empagliflozin, on hyperglycemia in a novel rat model of non-obesity type 2 diabetes with enlarged kidney (DEK).MethodsMale DEK rats with non-fasting blood glucose concentrations ≤300 mg/dl and >300 mg/dl were classified as nondiabetic and diabetic, respectively. Groups of nondiabetic (control) and diabetic (DM-cont) rats were fed standard chow for 12 weeks, whereas another group of diabetic (DM-empa) rats was fed standard chow containing empagliflozin (300 mg/kg/day) for 12 weeks. Blood glucose, body weight, glucose tolerance, food and water intake, urinary volume, plasma and urinary biochemical parameters, and bone mineral density were measured, and their kidneys and pancreas histologically analyzed.ResultsTreatment with empagliflozin reduced blood glucose concentration and food intake in diabetic rats, but inhibited loss of adeps renis and led to body weight gain. Empagliflozin attenuated polyuria and polydipsia but increased plasma concentrations of total cholesterol, sodium and total protein toward normal level. Empagliflozin also significantly reduced urinary excretion of proteins and electrolytes and restored bone mineral density and plasma concentrations of valine and isoleucine to normal levels. Moreover, dilation of renal tubules and kidney enlargement were not attenuated in the DM-empa group.ConclusionThe response of DEK rats to empagliflozin differed from that of other diabetic animal models, suggesting that DEK rats have unique characters for studying and evaluating the multiple biological effects of SGLT2 inhibitors. These findings also indicted that empagliflozin could ameliorate systemic metabolism and improve renal tubule function in diabetic condition.

English

This study evaluated the anti-hyperglycemic potential of Stemonocoleus micranthus Harms. (Fabaceae) stem bark. Three models used in this study were: normoglycemic animal model, oral glucose tolerance test (OGTT) and alloxan-induced hyperglycemic model for acute and prolonged administration. Five (5) groups of rats (n=5) were used for all models; group 1 served as the control (received 2 ml/kg of distilled water; p.o.), groups 2, 3, and 4 received S. micranthus extract (SME) 100, 200, and 400 mg/kg, respectively, while group 5 received glibenclamide (GLI 0.2 mg/kg) as a reference drug. In the normoglycemic study, the % reduction in blood glucose concentration (BGC) was 22.24, 29.97, 30.03 and 37.28% for SME (100, 200 and 400 mg/kg) and GLI, respectively. In the OGTT study, suppression in BGC was statistically significant (p&lt;0.05) at 120 min for the 400 mg/kg SME group. The glycemic changes (%) observed in SME (100, 200 and 400 mg/kg) treated rats were 3.4, 0.86 and 0.45%, respectively at the 120 min relative to 0 min values. Also, oral administration of SME (100, 200, 400 mg/kg) and GLI significantly (p&lt;0.05) reduced the BGC to varying degrees in alloxan-induced hyperglycemic rats. The SME at 400 mg/kg produced the highest percentage diminution in BGC of 23.26 and 67.66% for the acute and the prolonged anti-hyperglycemic study respectively, whereas the standard drug, GLI, exhibited 73.55 and 66.10%, respectively. Histopathological studies revealed protection from the harmful effect of alloxan on the kidney and liver by SME-treatment after 28 days as against GLI treated group where there was evidence of mild hepatosis. From the results, it can be deduced that S. micranthus stem bark possesses anti-hyperglycemic effects, thus scientifically corroborating with the folkloric use.&nbsp; Key words: Stemonocoleus micranthus, alloxan, glibenclamide, normoglycemia, hyperglycemia.

Antidiabetic Property of a Fraction of the Methanol Extract of the Seeds of Abrusprecatorius in Alloxan-induced Diabetic Rats

Introduction: Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects of insulin secretion and/or increased cellular resistance to insulin. Abrusprecatoriushas been used for the treatment of various ailments including diabetes mellitus. This study is aimed at evaluating the possible anti-diabetic effect of the methanol fraction 2 (F2) of the seeds of Abrusprecatoriusin alloxan-induced diabetic Wistar albino rats.&#x0D; Methods: The methanol extract of the seeds of A. precatorius Linn Fabaceae was fractionated by Sephadex G15. Diabetes was induced by a single intraperitoneal administration of 150 mg/kg bodyweight of alloxan. Acute toxicity (LD50) study was done using Lorke’s method. The antidiabetic activities of Fraction 2 (F2) and the biochemical parameters were investigated using standard diagnostic methods.&#x0D; Results: The value of the LD50 is 529.2 mg/kg bw. Oral doses (5, 10 and 20 mg/kg bw.) of the extract caused a dose-dependent significant (p&lt;0.05) reductions in blood glucose concentrations compared with diabetic untreated controls. There were significant decreases (p&lt;0.05) in the total cholesterol and triacylglycerol levels of rats in the treatment groups compared with the diabetic untreated group. The groups that were treated with glibenclamide, 5 mg/kg of the fraction, 20mg/kg of the fraction and the group that was pre-treated with 10mg/kg of the fraction before the induction of diabetes showed a significant decrease (p&lt;0.05) in the concentration of low-density lipoprotein and significant increase (p&lt;0.05) in high-density lipoprotein concentrations compared with the diabetic untreated group. The protein level increased non-significantly (p&gt;0.05) in all the test groups compared with the diabetic untreated control group except the pre-treated group which increased significantly (p&lt;0.05).&#x0D; Conclusion: The results obtained from this study revealed that the methanol fraction of A. precatorius has antidiabetic property which can be as a result of the important phytochemicals found in the F2 fraction. Fraction 2 (F2) however showed improvement in lipid profile.

Effect of acute football activity and physical fitness on glycaemic and insulinaemic responses in adolescents

ABSTRACT The present study examined the metabolic responses to an acute bout of football and the overall and moderating role of physical fitness on these responses, in adolescents. Thirty-six adolescents (16 girls, 20 boys; 12.6±0.5 y) completed two trials (60-min football and 60-min seated rest) separated by 7-d. Capillary blood samples were taken at baseline (60-min prior to exercise/rest), immediately, 30- and 60-min post-exercise and 30-, 60- and 120-min following a standardised lunch (1.5-, 2- and 3-h post-exercise), for the determination of blood glucose and plasma insulin concentrations. The median split of distance covered on the multi-stage fitness test was used to define high- and low-fit groups. Overall plasma insulin tAUC following lunch was lower in high-fit participants compared to low-fit (high-fit: 3784.2±1653.1 pmol·L−1x120min, low-fit: 6457.3±3290.7 pmol·L−1x120min; p<0.001), although there was no acute effect of the football session (p>0.05). Football reduced blood glucose concentration 1-h post-exercise compared to control (exercise: 3.8±0.6 mmol·L−1, rest: 4.6±0.8 mmol·L−1; p<0.001), but this was similar for the high- and low-fit participants (p>0.05). Blood glucose tAUC was not affected by exercise or physical fitness (p>0.05). These data emphasise the importance of physical fitness for metabolic health in adolescents, as well as the utility of football as a popular form of games-based activity for improving glucose regulation.

Evaluation of Antihyperglycemic Effect of Extract of Moringa stenopetala (Baker f.) Aqueous Leaves on Alloxan-Induced Diabetic Rats.

BackgroundDiabetes is a serious metabolic disorder with complications that result in significant morbidity and mortality. Current drugs used for diabetes therapy are not free from side effects and do not restore normal glucose homeostasis. Therefore, the purpose of this study is to evaluate the antidiabetic effect of Moringa stenopetala (Baker f.) aqueous leaves extract.MethodsThirty rats of weight 90–150 gram were distributed to five groups (n= 6). Then labelled as diabetic control (DC), normal control (NC), extract treated (MS 250 and 500mg/kg), and glibenclamide treated (GL 5mg/kg). The experimental rats were induced by intra-peritoneal injection of Alloxan monohydrate at a dose of 180 mg/kg after dissolving in normal saline. Clinical biochemistry such as AST, ALT, ALP, urea, creatinine, and cholesterol, blood glucose level, histopathological and preliminary phytochemical screening were evaluated.ResultsPhytochemical tests revealed the presence of different secondary metabolites. Alkaloid, flavonoid, tannin, saponin, phytosteroids, phenols and terpenoids. Moringa stenopetala (Baker f.) leaves aqueous extract (250 and 500mg/kg) improved the body weight of rats, showed remarkable reduction in blood glucose concentration (P<0.05), and significantly decreased serum urea, creatinine, ALT, AST and ALP (P < 0.05). Levels of serum cholesterol remained unaltered in the experimental groups when compared with diabetic control. Histopathology of non-treated rats showed deterioration of insulin producing pancreas cells; nevertheless, β-cells restoration was observed due to administration of Moringa stenopetala (Baker f.) aqueous leaves extract.ConclusionIt is possible to conclude that oral administration of Moringa stenopetala (Baker f.) aqueous leaf extracts (250mg/kg and 500mg/kg) for 28 days showed beneficial effects on antihyperglycemia, improved body weight and Alloxan damaged pancreatic β-cells, and restored biochemical changes.

Effect of Eurotium cristatum fermentation on the α-glucosidase inhibitory activity of mulberry leaves flavonoid extract

Diabetes has become a global chronic disease and alpha-glucosidase inhibitors is an effective ways of treating it. Flavonoids are a group of substances in mulberry leaves that have α-glucosidase inhibitory properties and can reduce blood glucose concentrations effectively. In this paper, flavonoids from mulberry leaves fermented by Eurotium cristatum CY-1 will be used to investigate their inhibitory properties on α-glucosidase. The results indicated that the fermentation would increase the total flavonoid content of mulberry leaves by 196.7%. Meanwhile, the α-glucosidase inhibition efficiency of flavonoids extracted from the fermented mulberry leaves was also enhanced under the same concentration. The IC50 values of the flavonoids extracted from 8 d fermented mulberry leaves and the unfermented mulberry leaf was 4.14 μg/mL and 10.26 μg/mL, respectively. This article will provide a reference for using microbial fermentation to enrich active ingredients of functional Chinese medicine herbs.