Reduced Blood Glucose Concentrations Research Articles

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.

Naturally Occurring SGLT2 Inhibitors: A Review.

With an increasing incidence of diabetes mellitus globally due to various factors, including unhealthy lifestyle, there is a need for developing novel drugs for the management of diabetes. This chronic metabolic disorder results in high blood glucose levels due to the body's inability to reduce the concentration of glucose. The decreased secretion of insulin and increased resistance to insulin action contribute to the development of diabetes mellitus. There have been efforts to target pathways involved in the metabolism of blood glucose. It seems that most of the currently applied antidiabetic medications are associated with unwanted side effects. Hence, it appears that plant-derived chemicals can be considered as potential candidates in the management of diabetes. Sodium-glucose cotransporter inhibitors (SGLT2i) are synthetic hypoglycemic medications approved for managing patients with diabetes in lowering blood glucose. SGLT2i reduces blood glucose concentration by enhancing its urinary excretion and inhibition of its absorption through the kidney. It has been demonstrated that some of the naturally occurring nutraceutical agents can imitate the action of SGLT2i and, consequently, diminish the level of blood glucose. At the present review, we have discussed the phytochemicals that act like SGLT2i to decrease blood glucose level.

IL-17A is involved in diabetic inflammatory pathogenesis by its receptor IL-17RA.

The participation of interleukin (IL)-17A in diabetic pathogenesis is suggested in animal models of autoimmune diabetes and in patients with type 1 diabetes (T1D), but with some contradictory results. Particularly, evidence for a direct injury of IL-17A to pancreatic β cells is lacking. We showed that IL-17A deficiency alleviated diabetic signs including hyperglycemia, hypoinsulinemia, and inflammatory response in Ins2Akita (Akita) mice, a T1D model with spontaneous mutation in insulin 2 gene leading to β-cell apoptosis. IL-17A enhanced inflammatory reaction, oxidative stress, and cell apoptosis but attenuated insulin level in mouse insulin-producing MIN6 cells. IL-17A had also a synergistic destruction to MIN6 cells with streptozotocin (STZ), a pancreatic β-cell-specific cytotoxin. Blocking IL-17 receptor A (IL-17RA) reduced all these deleterious effects of IL-17A on MIN6 cells. The results demonstrate the role and the importance of IL-17A in T1D pathogenesis and suggest a potential therapeutic strategy for T1D targeting IL-17A and/or IL-17RA.

D-ribose-L-cysteine improves hormonal imbalance, spermatogenic dysregulation, and redox status in streptozotocin-diabetic rats

D-ribose-L-cysteine is a pro-drug that is derived from L-cysteine which is reported to upsurge the cellular levels of glutathione. Diabetes mellitus is a metabolic disease that causes oxidative imbalance resulting in an impairment of the steroidogenic function and reproductive dysfunctions. This study is to investigate the potency of D-ribose-L-cysteine in reversing hyperglycemia and reproductive histopathological alterations in streptozotocin-diabetic rats. Diabetes was induced in adult male Wistar rats with a single intraperitoneal injection of 70 mg/kg b.w. streptozotocin. The hyperglycemic rats were thereafter treated orally with D-ribose-L-cysteine (100 mg/kg b.w.) and metformin (30 mg/kg b.w.) respectively once daily for a period of 17 days. Blood glucose concentration, reproductive hormonal assays, seminal fluid analysis, testicular anti-oxidant enzymes, tissue protein, and histopathological investigations were done to determine the effects of D-ribose-L-cysteine in streptozotocin-diabetic rats. Treatment with D-ribose-L-cysteine was associated with reduction in blood glucose concentration, increased body weight, increased tissue protein, reduced lipid peroxidation, and increase in anti-oxidant enzymes compared with the diabetic control. D-ribose-L-cysteine-treated rats also showed improved tubular cellularity and cytoarchitectural integrity relative to the diabetic control. In this study, D-ribose-L-cysteine, a synthetic pro-drug, proved to be able to reverse endocrine imbalance and spermatogenic alterations associated with diabetes by eliminating oxidative stress.

Fumaryl Diketopiperazine Microspheres Platform Design for Protein Pulmonary Delivery in Diabetes Rats Model.

The cornerstone of this study was to formulate and optimize fumaryl diketopiperazine (FDKP) microspheres of insulin-load (INS@FDKP-MPs) with the aid of Box-Behnken design (BBD) to enhance insulin bioavailability. The property characterization of INS@FDKP-MPs was studied and the stability study was confirmed by evaluating the effect on sample appearance, insulin and related protein content, hygroscopicity. At the same time, the pharmacodynamics of INS@FDKP-MPs was evaluated by testing the concentration of blood glucose of the diabetic model rats under different conditions. The optimized formulation of INS@FDKP-MPs drug loading microspheres is 2.37 h of stirring time, 4.64 of pH value and 23.11% of the drug ratio. Under this condition, the results of optimized formulation showed the average microspheres size of 1.69 nm, the drug loading rate of 10.95%. The size of microspheres is all below 3 m and the pulmonary deposition rate in stage 3 and stage 4 is more than twice that of other stages. The results of stability confirmed that INS@FDKP-MPs had good stability within three months. Futhermore, pharmacodynamics results indicated that inhaled insulin (Tmin 60 to 90 min) could rapidly be absorbed into the systemic circulation compared to subcutaneous injection (Tmin 120 min); Inhaled insulin can continuously reduce blood glucose concentration within 120 minutes, which is significantly faster than subcutaneous injection (180 minutes). That is stand for reducing the possibility of hypoglycemia. Through Pulmonary Administration, INS@FDKP-MPs can be efficiently and effectively absorbed into the systemic circulation with good pharmacodynamics and the ability to lower blood glucose levels.

Beneficial role of Stevia rebaudiana dry extract on the blood glucose reduction in the chronic diabetes mellitus

Introduction: Prolonged hyperglycemia may lead to several detrimental microvascular or macrovascular complications in the chronic diabetes mellitus. Thus, achieving normal glycemic condition remains the most important strategy in the diabetes mellitus. Stevia rebaudiana plays an important role on the blood glucose reduction, however, its role in the chronic diabetes mellitus has not been fully elucidated yet.Method: Stevia rebaudiana dry extract (400 mg/kg BW) were given daily by oral gavage for 84 days in rat with diabetes. The measurement of blood glucose concentration were done monthly during the study. Urine output was analyzed on the day 1 and 84. Additionally, lipid profile were measured on the day 84.Results: Compared to the normal rat, significant hyperglycemia were observed in the diabetic rat. Blood glucose concentration tends to decrease in the rat received Stevia rebaudiana extract (St), however, significant difference was achieved on the day 84 of the study confronted to the diabetic rats. Moreover, lower concentration of plasma cholesterol concentration and urine output reduction was significantly observed in the St rat compared to the D rat on the day 84.Discussion: Daily intake of Stevia rebaudiana extract on its therapeutic doses may play beneficial role in the chronic diabetes mellitus by gradually reduced blood glucose concentration, urine output and plasma cholesterol concentration. However, further cellular analysis were required to explicate the exact mechanism.International Journal of Human and Health Sciences Vol. 05 No. 01 January’21 Page: 22-26