Evaluation of acute oral toxicity, anti-diabetic and antioxidant effects of Aloe vera flowers extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloe vera (L.) Burm.f. is widely used in various traditional systems of medicine worldwide. Since over 5000 years ago, several cultures have used A. vera extract medicinally for conditions ranging from diabetes to eczema. It has been shown to reduce the symptoms of diabetes by enhancing insulin secretion and protecting pancreatic islets. AIM OF THE WORK: This research study aimed to investigate the in-vitro antioxidant effect, the acute oral toxicity, and the possible pharmacological in-vivo anti-diabetic activity with histological examination of the pancreas of the standardized deep red A. vera flowers methanolic extracts (AVFME). MATERIALS AND METHODS: The liquid-liquid extraction procedure and TLC technique were used to investigate chemical composition. Total phenolics and flavonoids in AVFME were quantified by Folin-Ciocalteu and AlCl3 colorimetric methods, respectively. The present study involved evaluating the in-vitro antioxidant effect of AVFME using ascorbic acid as the reference standard, an acute oral toxicity study by using thirty-six albino rats and different concentrations of AVFME (200 mg/kg, 2, 4, 8 and 10 g/kg b.w.). Furthermore, the in-vivo anti-diabetic study was performed on alloxan-induced diabetes in rats (120 mg/kg, I.P.) and two doses of AVFME (200 and 500 mg/kg b.w., orally) were used as compared to glibenclamide (5 mg/kg, orally) as a standard hypoglycemic sulfonylurea medication. A histological examination of the pancreas was performed. RESULTS: AVFME resulted in the highest phenolic content of 150.44 ± 4.62 mg gallic acid equivalent per gram (GAE/g) along with flavonoid content of 70.38 ± 0.97 mg of quercetin equivalent per gram (QE/g). An in-vitro study revealed that the antioxidant effect of AVFME was strong as ascorbic acid. The results of the in-vivo studies showed that the AVFME didn't cause any apparent toxicity signs or death in all groups at different doses which proves the safety of this extract with a wide therapeutic index. The antidiabetic activity of AVFME demonstrated a considerable drop in blood glucose levels as glibenclamide, without severe hypoglycemia or significant weight gain which is considered an advantage of AVFME over glibenclamide use. The histopathological study of pancreatic tissues confirmed the protective effect of AVFME on the pancreatic beta-cells. The extract is proposed to have antidiabetic activity through inhibition of α-amylase, α-glucosidase, and dipeptidyl peptidase IV (DPP-IV). Molecular docking studies were conducted to understand possible molecular interactions with these enzymes. CONCLUSION: AVFME represents a promising alternative source of active constituents against diabetes mellitus (DM) based on its oral safety, antioxidant, anti-hyperglycemic activities, and pancreatic protective effects. These data revealed the antihyperglycemic activity of AVFME is mediated by pancreatic protective effects while significantly enhancing insulin secretion through increasing functioning beta cells. This suggests that AVFME has the potential as a novel antidiabetic therapy or a dietary supplement for the treatment of type 2 diabetes (T2DM).

Crude extract from Euphorbia prostrata extended curative period of glibenclemide in alloxan-induced diabetic rats.

OBJECTIVES: Euphorbia prostrata is traditionally used alongside antidiabetic agents to manage diabetes. Bioactive ingredients of medicinal herbs may alter the overall pharmacokinetics of antidiabetic agents. METHODS: We assessed hypoglycemic activities of ethanolic plant extract (EPE) singly and its effects on antidiabetic properties of gliclazide, glibenclemide and metformin in allaxonized rats. Varying concentrations of EPE (250 and 500 mg/kg) with or without metformin (10 mg/kg), glibenclemide (2 mg/kg) and gliclazide (5 mg/kg) were orally administered to evaluate herb-drug interaction. RESULTS: The levels of blood glucose declined significantly after treatment with metformin, glibenclemide and gliclazide singly (p<0.01) or concomitantly with EPE (p<0.001). Concentration dependent mild to moderate reduction (5.2 and 10.0%) was registered in blood glucose for 250 and 500 mg/kg of EPE respectively. The overall reduction in blood glucose due to combined treatment with EPE and standard agents was additive. On the other hand, synergistic herb-drug interaction was registered for insulin levels in rats that received glibenclamide and gliclazide alongside EPE. Extract with metformin had antagonistic insulin outcome. Regarding the duration of hypoglycemic activities, periodical changes were similar in case of glibenclamide and gliclazide separately or in combination with EPE. However, in case of metformin with extract, the blood glucose continued to decline for 14 h and retained at 15.0% below the baseline values even after 24 h of treatment. CONCLUSIONS: In conclusion, the extract itself had weak hypoglycemic effects but prolonged the therapeutic duration of metformin to more than 24 h when administered combinedly.

The protective effect of green tea on diabetes-induced hepato-renal pathological changes: a histological and biochemical study.

We investigated the protective effect of green tea on diabetic hepato-renal complications. Thirty male Wistar rats were randomly divided into five equal groups: normal control, diabetic control, glibenclamide-treated, green tea-treated, and combined therapy-treated groups; ethical approval number "BERC-014-01-20." After eight weeks, animals were sacrificed by CO2 euthanasia method, liver and kidney tissues were processed and stained for pathological changes, and blood samples were collected for biochemical analysis. Diabetic rats showed multiple hepato-renal morphological and apoptotic changes associated with significantly increased some biochemical parameters, while serum albumin and HDL decreased significantly compared to normal control (p < .05). Monotherapy can induce significant improvements in pathological and biochemical changes but has not been able to achieve normal patterns. In conclusion, green tea alone has a poor hypoglycaemic effect but can reduce diabetic complications, whereas glibenclamide cannot prevent diabetic complications. The addition of green tea to oral hypoglycaemic therapy has shown a potent synergistic effect.

Chitosan-Encapsulated Nano-selenium Targeting TCF7L2, PPARγ, and CAPN10 Genes in Diabetic Rats.

This study investigates the antidiabetic and antioxidant potential of chitosan-encapsulated selenium nanoparticles in streptozotocin-induced diabetic model. Glibenclamide was used as a reference antidiabetic drug. Forty-eight adult male Wistar rats were used along the study and divided equally into 6 groups of (I) normal control, (II) chitosan-encapsulated selenium nanoparticles (CTS-SeNPs), (III) glibenclamide, (IV) streptozotocin (STZ), (V) STZ + CTS-SeNPs, and (VI) STZ + Glib. The animals were sacrificed on the 35th day of the experiment. Serum glucose, insulin, IGF-1, ALT, AST, CK-MB, oxidative stress, lipid profile, and inflammatory parameters were subsequently assessed. Also, the expression level of TCF7L2, CAPN10, and PPAR-γ genes were evaluated using qPCR. In addition, histopathological studies on pancreatic tissue were carried out. The results revealed that STZ induced both diabetes and oxidative stress in normal rats, manifested by the significant changes in the studied parameters and in the physical structure of pancreatic tissue. Oral administration of CTS-SeNPs or Glib results in a significant amelioration of the levels of serum fasting blood glucose, insulin, IGF-1, AST, ATL, and CK-MB as compared with STZ-induced diabetic rats. CTS-SeNPs and Glib diminished the level of lipid peroxidation, increased total antioxidant capacity level, as well as possessed strong inhibition against serum α-amylase and α-glucosidase activities. Diabetic animals received CTS-SeNPs, or Glib demonstrated a significant (p < 0.05) decrease in the expression level of TCF7L2 and CAPN10 genes with a significant increase in the expression level of PPAR-γ gene, compared to STZ group. The above findings clarify the promising antidiabetic and antioxidant effect of CTS-SeNPs, recommending its inclusion in the currently used protocols for the treatment of diabetes and in the prevention of its related complications.

Stink bean (Parkia speciosa) empty pod: a potent natural antidiabetic agent for the prevention of pancreatic and hepatorenal dysfunction in high fat diet/streptozotocin-induced type 2 diabetes in rats.

The present study investigated the effect of polyphenol-rich extract of Parkia speciosa (PPS) against pancreatic and hepatorenal dysfunction in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetes. Diabetic rats were treated with PPS (100 and 400 mg/kg) and glibenclamide. The results revealed that diabetic rats displayed marked hyperglycaemia, hyperlipidaemia, hypoinsulinemia as well as alterations in serum renal and kidney function markers. Furthermore, diabetic rats showed significant increase in hepatorenal level of malonaldehyde as well as suppression of antioxidant enzyme activities. Whereas, diabetic rats that received PPS displayed marked attenuation in most of the aforementioned parameters compared to the untreated diabetic rats. Additionally, histological examination revealed restoration of histopathological alterations of the pancreas, liver, and kidney of PPS treated diabetic rats. In conclusion, the results demonstrated that PPS could decrease serum lipids and blood glucose level, enhance insulin level and hepatorenal antioxidant capacity, as well as ameliorate hepatorenal dysfunction in rats.

Vulgarin, a Sesquiterpene Lactone from Artemisia judaica, Improves the Antidiabetic Effectiveness of Glibenclamide in Streptozotocin-Induced Diabetic Rats via Modulation of PEPCK and G6Pase Genes Expression.

The current investigation assessed the effect of the eudesmanolid, Vulgarin (VGN), obtained from Artemisia judaica (A. judaica), on the antidiabetic potential of glibenclamide (GLB) using streptozotocin (STZ) to induce diabetes. Seven groups of rats were used in the study; the first group received the vehicle and served as normal control. The diabetic rats of the second to the fifth groups were treated with the vehicle (negative control), GLB at 5 mg/kg (positive control), VGN at 10 mg/kg (VGN-10) and VGN at 20 mg/kg (VGN-20), respectively. The diabetic rats of the sixth and seventh groups were administered combinations of GLB plus VGN-10 and GLB plus VGN-20, respectively. The diabetic rats treated with GLB plus VGN-20 combination showed marked improvement in the fasting blood glucose (FBG), insulin and glycated hemoglobin (HbA1c), as well as the lipid profile, compared with those treated with GLB alone. Further, the pancreatic tissues of the diabetic rats that received the GLB+VGN-20 combination showed superior improvements in lipid peroxidation and antioxidant parameters than those of GLB monotherapy. The insulin content of the ß-cells was restored in all treatments, while the levels of glucagon and somatostatin of the α- and δ-endocrine cells were reduced in the pancreatic islets. In addition, the concurrent administration of GLB+VGN-20 was the most effective in restoring PEPCK and G6Pase mRNA expression in the liver. In conclusion, the results demonstrated that the GLB+VGN-20 combination led to greater glycemic improvement in diabetic rats compared with GLB monotherapy through its antioxidant effect and capability to modulate PEPCK and G6Pase gene expression in their livers.

Phytochemical Analysis and hypoglycemic potential of Filago hurdwarica (Wall. ex DC.) Wagenitz in alloxan induced diabetic mice.

Plants have profound therapeutic benefits, more economical treatments, fewer side effects, and a relatively cheap cost, making them a source of drugs for protective, preventative, curative, or conducive purposes and creating novel phytomedicines. Plant derived medicines are relatively safe compared to synthetic medicines. Many plants have proved to successfully aid in the treatment of diabetes including Filago hurdwarica (Wall. ex DC.) Wagenitz. The current investigations were therefore designed to assess the phytochemical, antioxidant, antidiabetic, and antihyperlipidemic activities of F. hurdwarica. The phytochemical investigations and antioxidant activities of different extracts were carried out using standard chemical tests, DPPH, and H2O2 scavenging assays. F. hurdwarica plant extract in Hydromethanolic solution were prepared by Soxhletation method and stored in refrigerator at 4°C for two days before use. Swiss Albino mice were made diabetic by a single dose of alloxan (150 mg/kg). Hydromethanolic plant extract and fractions of F. hurdwarica were screened for antidiabetic activity and given to the alloxan-induced diabetic mice at a concentration of 150-250 mg/kg of body weight in different groups of 6 diabetic mice each orally once a day for 15 days. Glibenclamide is also given to another group to as a standard drug to support the result at a dose of 10 mg/kg of body weight orally once a day for 15 days. Blood glucose levels and body weights of mice were measured on 0, 4, 7, 11 and 15th days. The study found that the extract was safe up to the dose level of 2000 mg/kg and the dose response effect of chloroform extract (150-250 mg/kg) of F. hurdwarica showed expressive antihyperglycemic effects and also improved other altered biochemical parameters associated with diabetes. The FTIR and XRD spectra demonstrated the occurrence of phenols, alcohols, alkenes, alkyl halides, ketones, and aromatic compounds and confirmed the amorphous nature of the extract. GC-MS spectral analysis showed the tentative presence of 31 phytochemical constituents in the chloroform extract of F. hurdwarica with different retention time. To conclude, the chloroform extract (250 mg/kg) of F. hurdwarica revealed considerable antioxidant, antihyperglycemic, and antihyperlipidemic potential and is safe for treating diabetes and related complications.

Vitamin D Supplementation Could Enhance the Effectiveness of Glibenclamide in Treating Diabetes and Preventing Diabetic Nephropathy: A Biochemical, Histological and Immunohistochemical Study.

Diabetes mellitus is an oxidative stress-related disease characterized by hyperglycemia and a variety of complications, including nephropathy. Vitamin D has variable functions extending beyond the calcium metabolism to prevent oxidative tissue damage. We aimed to investigate whether vitamin D supplements could enhance Glibenclamide's effectiveness in treating diabetes and minimize the risk of associated pathology. Wistar rats were divided into normal control (n = 10) and diabetic (n = 30), where animals received two low doses of Streptozotocin 30 mg/kg/BW intraperitoneally to develop diabetes. The diabetic rats were then randomly divided into three equal groups: untreated, treated with Glibenclamide (0.6 mg/kg), and treated with Glibenclamide and Vitamin D3 (500 IU/kg). After eight weeks, the animals were sacrificed, and blood samples and kidney tissues were collected to evaluate biochemical, anti-oxidant, and pro-inflammatory cytokine levels and histological and immunohistochemical changes. Diabetic animals had significantly increased fasting blood glucose, lipid profile, blood urea, serum creatinine, and Malondialdehyde levels, whereas serum insulin, albumin, and the anti-oxidant enzymes superoxide dismutase and catalase were significantly decreased compared to normal control (p < 0.01). Furthermore, some renal histological changes were observed together with significantly increased immunoreactivity of anti-p53, anti-TNF-α, and anti-IL-6 antibodies when compared to the normal control. All abnormal parameters improved significantly with Glibenclamide therapy (p < 0.01), but combination therapy with vitamin D produced a much better result. In conclusion, vitamin D supplementation along with anti-diabetic medication can help prevent or reduce the severity of diabetic nephropathy due to its potent antioxidant, anti-inflammatory, and anti-apoptotic properties.

Ameliorative role of Cyanus depressus (M.Bieb.) Soják plant extract against diabetes-associated oxidative-stress-induced liver, kidney, and pancreas damage in rats.

In this original article, we aimed to assess the ameliorative role of Cyanus depressus (CD) plant ethanolic extract treatment of streptozotocin (STZ)-induced liver, kidney, and pancreas damage in rats. The rats were divided into five groups (n = 7): control, CD, Diabetes mellitus (DM), DM + CD, and DM + glibenclamide (Gly). The DM groups were injected with a single dose of 50 mg/kg STZ intraperitoneally (i.p.). While the CD and DM + CD groups received 400 mg/kg/day intragastrically for 21 days, the DM + Gly group received 3 mg/kg/day of Gly intragastrically throughout the experiment. Statistically significance was accepted as p < .05. According to our liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) data, quinic acid, cosmosiin, nicotiflorin, apigenin, and protocatechuic acid were the major compounds, in descending order. Weekly blood glucose, serum glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and urea, malondialdehyde (MDA) (liver and pancreas), and blood glycosylated hemoglobin % (HbA1c %) were significantly decreased, whereas finally live body weights (LBWs), reduced glutathione (GSH), glutathione S-transferase (GST) and catalase (CAT) (pancreas), and pancreatic islet diameter and area were increased significantly in the CD-treated diabetic group. Moreover, CD administration was found to be effective in the protection of the histology of the liver, kidneys, and pancreatic islets in the STZ-induced rats. Consequently, we concluded that CD administration reduces hyperglycemia, oxidative stress, and histopathology in STZ-induced experimental rats by improving antioxidant defenses. PRACTICAL APPLICATIONS: Today, the prevalence of diabetes is increasing rapidly throughout the world and it causes complications such as kidney damage, blindness, amputations, and cardiovascular diseases. Despite medical technological advances, people's interest in medicinal herbal products is gradually increasing. Biochemical and histopathological findings showed that the use of the plant CD at the determined dose (400 mg/kg/day) in rats with DM by STZ had strong antioxidant and antidiabetic effects. CD may have a drug potential in preventing DM and its complications because of its phytochemical content including some phenolic acids such as quinic acid, cosmosiin, nicotiflorin, apigenin, and protocatechuic acid. Isolation of bioactive compounds from CD and investigation of their therapeutic effects could be planned as further studies.

Bridelia ferruginea Benth. (Euphorbiaceae) mitigates oxidative imbalance and lipotoxicity, with concomitant modulation of insulin signaling pathways via GLUT4 upregulation in hepatic tissues of diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Bridelia ferruginea Benth. (Euphorbiaceae) is among the medicinal plants commonly used for the management of type 2 diabetes (T2D) and its complications. AIM OF THE STUDY: The hepato-therapeutic effect of the butanol fraction of Bridelia ferruginea leaves was investigated in diabetic rats. METHODS: The butanol fraction of B. ferruginea was given to type 2 diabetic rats at both low and high doses (150 and 300 mg/kg bodyweight, respectively), while metformin and glibenclamide served as the standard anti-diabetic drugs. A normal toxicological group was administered a high dose of the fraction. At the end of the experimental period, the rats were sacrificed, and their livers and psoas muscle collected. The liver was assayed for oxidative stress markers, liver glycogen content, lipid metabolite profile (using GC-MS) and their metabolic pathways were analyzed using the MetaboAnalyst 5.0 online server. The expression of GLUT4 was also assayed in the liver and muscle as well as the identification of signaling pathways associated with GLUT4 expression using the Enrichr online server. In silico molecular docking was used to investigate the molecular interactions of some postulated compound found in B. ferruginea with GLUT4. The ability of the fraction to stimulate muscle glucose uptake was determined in isolated rat psoas muscle ex vivo. RESULTS: Treatment with the high dose of fraction caused an inhibition of lipid peroxidation as well as the elevation of catalase, SOD, glutathione reductase and glutathione peroxidase activities in the rat liver. There was an increased expression of GLUT4 in livers and muscles of diabetic rats following treatment with B. ferruginea. Treatment with the fraction also caused inactivation of diabetes-activated pathways and changes in the distribution of the hepatic lipid metabolites. Molecular docking analysis revealed strong molecular interactions of pyrogallol and sitosterol with GLUT4. CONCLUSIONS: These data illustrate the hepato-protective effect of B. ferruginea in diabetic rats which compare favorably with the tested anti-diabetic drugs (metformin and glibenclamide).

Creatine Supplementation in Type 2 Diabetic Patients: A Systematic Review of Randomized Clinical Trials.

Type 2 Diabetes Mellitus (DM) is the most common form of diabetes. The initial treatment of type 2 DM consists of the adoption of healthy lifestyle habits together with several classes of hypoglycemic agents. However, these medications are not always able to reduce the blood glucose levels in all patients. Therefore, creatine supplementation has emerged as a new putative candidate for type 2 DM treatment. This systematic review aimed to investigate the effects (benefits and harms) of creatine supplementation in patients with type 2 diabetes through a systematic review. The studies were searched in MEDLINE, EMBASE, LILACS, CENTRAL, SPORTDiscus, and CINAHL databases, without date or language restrictions. Methodological quality was assessed using the Cochrane risk-of-bias table. The certainty of the evidence was classified using the Grading of Recommendations Assessment, Development and Evaluation approach. Three randomized controlled trials (RCTs) were included (87 participants). Overall, the methodological quality was classified as unclear to a high risk of bias. Each trial compared creatine supplementation with a different control group (placebo, metformin, and glibenclamide). Creatine supplementation seems to be effective in decreasing glycemic levels and glycosylated hemoglobin concentrations compared to placebo. No difference was observed compared to metformin or glibenclamide with creatine, and all treatments were able to reduce blood glucose levels. No major adverse effects were observed. Based on the low certainty of evidence, creatine supplementation was shown to be a hypoglycemic intervention for patients with type 2 diabetes, without major adverse events reported. However, well- designed RCTs with larger sample sizes and long-term outcomes are needed to support this evidence.

siGCD: a web server to explore survival interaction of genes, cells and drugs in human cancers.

It is pivotal and remains challenge for cancer precision treatment to identify the survival outcome interactions between genes, cells and drugs. Here, we present siGCD, a web-based tool for analysis and visualization of the survival interaction of Genes, Cells and Drugs in human cancers. siGCD utilizes the cancer heterogeneity to simulate the manipulated gene expression, cell infiltration and drug treatment, which overcomes the data and experimental limitations. To illustrate the performance of siGCD, we identified the survival interaction partners of EGFR (gene level), T cells (cell level) and sorafenib (drug level), and our prediction was consistent with previous reports. Moreover, we validate the synergistic effect of regorafenib and glyburide, and found that glyburide could significantly improve the regorafenib response. These results demonstrate that siGCD could benefit cancer precision medicine in a wide range of advantageous application scenarios including gene regulatory network construction, immune cell regulatory gene identification, drug (especially multiple target drugs) response biomarker screening and combination therapeutic design.

Antidiabéticos orais no diabetes gestacional: revisão de literatura / Oral antidiabetics in gestational diabetes: literature review

O diabetes mellitus gestacional (DMG) é um distúrbio metabólico por déficit na produção e/ou ação insulínica. Tem relação direta com um constante estado catabólico associado com maior resistência à ação da insulina. Doença de difícil controle, implica risco materno-fetal elevado. O objetivo é estudar a eficácia das drogas antidiabéticas orais sobre o controle glicêmico no DMG e sua segurança quanto aos desfechos gestacionais e perinatais. Trata-se de revisão de literatura descritiva baseada em dados de artigos, livros-texto e guidelines emitidos nos últimos cinco anos. O antidiabético oral pode ser uma boa alternativa no controle do DMG em fase inicial da doença, na presença de distúrbio metabólico e como complemento da terapia com insulina. Entretanto, por causa de sua passagem placentária, há preocupações com seus efeitos fetais e perinatais. Estudos comparativos destacam a metformina no manejo do DMG, considerando principalmente a segurança materno-fetal.(AU)

Gestational diabetes mellitus (GDM) is a metabolic disorder caused by deficit in production and/or insulin action. It is directly related to a constant catabolic state associated with greater resistance to insulin action. Disease difficult to control, implies high maternal-fetal risk. To study the efficacy of oral antidiabetic drugs on glycemic control in GDM and its safety regarding gestational and perinatal outcomes. Descriptive literature review based on data from articles, textbooks and guidelines issued in the last five years. Oral antidiabetic can be a good alternative in the control of GDM in the initial phase of the disease, in the presence of metabolic disorder and as a complement to insulin therapy. However, there are concerns about its placental passage and perinatal effects. Comparative studies highlight metformin in the management of DMG considering mainly maternal-fetal safety.(AU)

Synergistic Effect of Omega-3 Fatty Acids and Oral-Hypoglycemic Drug on Lipid Normalization through Modulation of Hepatic Gene Expression in High Fat Diet with Low Streptozotocin-Induced Diabetic Rats.

Type 2 diabetes mellitus, which an outcome of impaired insulin action and its secretion, is concomitantly associated with lipid abnormalities. The study was designed to evaluate the combinational effect of omega-3 fatty acids (flax and fish oil) and glibenclamide on abnormal lipid profiles, increased blood glucose, and impaired liver and kidney functions in a high fat diet with low streptozotocin (STZ)-induced diabetic rats, including its probable mechanism of action. The male Wistar rats (n = 48) were distributed into eight groups. All animal groups except the healthy received a high fat diet (HFD) for 90 days. Further, diabetes was developed by low dose STZ (35 mg/kg). Diabetic animals received, omega-3 fatty acids (500 mg/kg), along with glibenclamide (0.25 mg/kg). Both flax and fish oil intervention decreased (p ≤ 0.001) serum triglycerides and very low density lipoprotein and elevated (p ≤ 0.001) high density lipoprotein levels in diabetic rats. Total cholesterol and low-density lipoprotein level was decreased (p ≤ 0.001) in fish oil-treated rats. However, it remained unaffected in the flax oil treatment group. Both flax and fish oil intervention downregulate the expression of fatty acid metabolism genes, transcription factors (sterol regulatory element-binding proteins-1c and nuclear factor-κß), and their regulatory genes i.e., acetyl-coA carboxylase alpha, fatty acid synthase, and tumor necrosis factors-α. The peroxisome proliferator-activated receptor gamma gene expression was upregulated (p ≤ 0.001) in the fish oil treatment group. Whereas, carnitine palmitoyltransferase 1 and fatty acid binding protein gene expression were upregulated (p ≤ 0.001) in both flax and fish oil intervention group.

Vitamin D supplementation improves SIRT1, Irisin, and glucose indices in overweight or obese type 2 diabetic patients: a double-blind randomized placebo-controlled clinical trial.

BACKGROUND: Vitamin D (VD) may increase sirtuin 1 (SIRT1) and subsequently PPAR-γ coactivator 1α (PGC-1α) and irisin levels and these improvements may reduce insulin resistance (IR). The aim was to assess the effects of vitamin D supplementation on SIRT1, irisin, and IR in overweight/obese type 2 diabetes (T2D) patients. METHODS: Ninety T2D males and females were recruited as a clinical trial study (mean of age and body mass index (BMI) of intervention and placebo groups were 50.05 ± 10.17 and 50.36 ± 10.2 yrs. and 31.37 ± 3.4 and 30.43 ± 3.2 kg/m2, respectively). The inclusion criteria were T2D, VD deficient, BMI > 25 kg/m2, and serum HbA1c < 8.5%. The exclusion criteria were using vitamin and mineral supplements, having any acute disease, recent modifying dose or type of drugs. The supplementation was 50,000 IU/week VD or placebo for 8 weeks. The demographic characteristics, anthropometrics, dietary intakes and physical activity status, sun exposure status, fasting blood sugar (FBS) and insulin, glycosylated hemoglobin (HbA1c), irisin, SIRT1, 25-hydroxy D3 (25(OH)VD), homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) were determined. The significant P-value was ≤0.05. RESULTS: The increase of serum VD, SIRT1, and irisin in the intervention group was significant (p < 0.001). HbA1c was decreased significantly by 1%. The changes in the other glucose indices (FBS, insulin, and IR) were non-significant. CONCLUSIONS: VD supplementation may improve T2D by decreasing HbA1c and increasing SIRT1 and irisin in VD deficient T2D patients. Further trials are suggested. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT201604202365N11. Registered 21/08/2016, http://en.irct.ir/trial/2019.

Comparing The Effect Of Electroacupuncture And Glibenclamide On Blood Glucose Level And Histological Markers Of Pancreas In Streptozotocin-Induced Diabetic Rats.

BACKGROUND: Diabetes lowers the quality of life and leads to several complications. Glibenclamide is a commonly used step-two treatment in diabetes but it causes weight gain, hypoglycemia and cardiovascular problems. Electroacupuncture (EA) can enhance insulin sensitivity and reduce blood glucose levels. OBJECTIVES: To compare the effects of EA plus glibenclamide (G) with single therapy by G or EA on blood glucose, pancreas volume, islet volume, ratio of islet volume to pancreas volume, apoptotic and beta cells numbers and body weight in diabetic rats. METHODS: Sixty adult male Wistar rats were randomly divided to 10 groups: 2 non-diabetic control groups and 8 diabetic groups (1 control and 7 experimental groups; D/G 2.5, D/G 5, D/G 10 mg/kg, EA, D/EA/G 2.5, D/EA/G 5, and D/EA/G 10). Diabetes was induced by intraperitoneal injection of 35 mg/kg streptozotocin with high-fat diet. At the end of the course, blood samples were obtained and pancreases were dissected. RESULTS: EA was as effective as D/G 5 and D/G 10 in all outcomes. Combination therapy of EA and glibenclamide 5 and 10 mg/kg resulted in a better glucose-lowering effect, greater islet volume and ratio of islet volume to pancreas volume than single therapies (P < .05). EA increased the pancreas volume as much as the combination therapies (P > .05). CONCLUSION: Combination of EA and glibenclamide 5 showed the best effects on blood glucose, islet volume and ratio of islet to pancreas volume. Combination of EA and glibenclamide 2.5 illustrated the best effects on apoptotic and beta cell number of diabetic rats.

The Use of Non-insulin Agents in Gestational Diabetes: Clinical Considerations in Tailoring Therapy.

PURPOSE OF REVIEW: To assess evidence to date for use of non-insulin agents in treatment of gestational diabetes mellitus. RECENT FINDINGS: There has been increasing interest in the use of non-insulin agents, primarily metformin and glyburide (which both cross the placenta). Metformin has been associated with less maternal weight gain; however, recent studies have shown a trend toward increased weight in offspring exposed to metformin in utero. Glyburide has been associated with increased neonatal hypoglycemia. Glycemic control during pregnancy is essential to optimize both maternal and fetal outcomes. There are a myriad of factors to consider when designing treatment programs including patient preference, phenotype, and glucose patterns. While insulin is typically recommended as first-line, some women refuse or cannot afford insulin and in those cases, non-insulin agents may be used. Further studies are needed to assess treatment in pregnancy, perinatal outcomes, and particularly long-term metabolic profiles in mothers and offspring.

Betanin exhibits significant potential as an antihyperglycemic and attenuating the glycoprotein components in streptozotocin-nicotinamide-induced experimental rats.

This study hypothesized to evaluate the effect of betanin, a chromoalkaloid on plasma and altered tissues glycoprotein components in streptozotocin-nicotinamide-induced diabetic rats. Diabetes was induced by a single intraperitoneal (i.p.) injection of streptozotocin (45 mg/kg b.w.) dissolved in 0.1 M citrate buffer (pH 4.5) 15 min after the i.p. administration of nicotinamide (110 mg/kg b.w.). Experimental rats were administered betanin at the dose of 20 mg/kg b.w. and glibenclamide (600 µg/kg b.w.) once a day for 30 days. Diabetic rats revealed significant (p < 0.05) increase in the levels of glucose, HbA1C, hexose, hexosamine, sialic acid and fucose in the plasma; decrease in the levels of plasma insulin, Hb and sialic acid in the liver and kidney; significant (p < 0.05) increase in hexose, hexosamine and fucose in the liver and kidney. Moreover, periodic acid-Schiff staining of tissues revealed positive-stain accumulation in diabetic rats. On co-supplementation of betanin and glibenclamide to diabetic rats for the period of 30 days brought back the levels of plasma and tissues glycoprotein components. Based on the present study, we propose that betanin possesses significant protective effect on glycoprotein components in plasma and tissue of diabetic rats.

Orofacial antinociceptive effect of Mimosa tenuiflora (Willd.) Poiret.

Mimosa tenuiflora (Willd.) Poiret, popularly known in Brazil as "jurema-preta" is widely used against bronchitis, fever, headache and inflammation. Its antioxidant, anti-inflammatory and antinociceptive potential has already been reported. To assess the orofacial antinociceptive effect of M. tenuiflora, ethanolic extracts of M. tenuiflora (leaves, twigs, barks and roots) were submitted to in vitro tests of antioxidant activity. The extract with the highest antioxidant potential was partitioned and subjected to preliminary chemical prospecting, GC-MS, measurement of phenolic content and cytotoxicity tests of the fraction with the highest antioxidant activity. The nontoxic fraction with the highest antioxidant activity (FATEM) was subjected to tests of acute and chronic orofacial nociception and locomotor activity. The possible mechanisms of neuromodulation were also assessed. The EtOAc fraction, obtained from the ethanolic extract of M. tenuiflora barks, was the one with the highest antioxidant potential and nontoxic (FATEM), and Benzyloxyamine was the major constituent (34.27%). FATEM did not alter the locomotor system of mice and reduced significantly the orofacial nociceptive behavior induced by formalin, glutamate, capsaicin, cinnamaldehyde or acidic saline compared to the control group. FATEM also inhibited formalin- or mustard oil-induced temporomandibular nociception. In addition, it also reduced mustard oil-induced orofacial muscle nociception. However, FATEM did not alter hypertonic saline-induced corneal nociception. Neuropathic nociception was reversed by treatment with FATEM. The antinociceptive effect of FATEM was inhibited by naloxone, L-NAME and glibenclamide. FATEM has pharmacological potential for the treatment of acute and neuropathic orofacial pain and this effect is modulated by the opioid system, nitric oxide and ATP-sensitive potassium channels. These results lead us to studies of isolation and characterization of bioactive principles.

Pharmacological treatment of gestational diabetes mellitus: point/counterpoint.

Controversies persist over the most efficacious pharmacologic treatment for gestational diabetes mellitus. For purposes of accuracy in this article, the individual American College of Obstetricians and Gynecologists Practice Bulletin and American Diabetes Association Standards of Medical Care positions on each issue are quoted and then deliberated with evidence of counter claims presented in point/counterpoint. This is a review of all the relevant evidence for the most holistic picture possible. The main issues are (1) which diabetic drugs cross the placenta, (2) the quality of evidence and data source validity, (3) the rationale for the designation of glucose control as the primary outcome in gestational diabetes mellitus, and (4) which drugs (metformin, glyburide, or insulin) are most effective in improving secondary outcomes. The concept that 1 drug fits all, whether it be insulin, glyburide, or metformin, is a fallacy. Different drugs provide certain benefits but not all the benefits and not to all patients. In addition, the steps in the gestational diabetes mellitus management decision path and the current cost of the use of insulin, glyburide, or metformin are addressed. In the future, we must consider studying the potential of diabetic drugs that currently are used in nonpregnancy and incorporating the concept of precision medicine in the decision tree to maximize pregnancy outcomes.