Decreased Blood Glucose Research Articles

Linagliptin improves diabetic kidney disease in rats by promoting mitochondrial biogenesis through the AMPK/PGC-1α/TFAM pathway

To investigate whether linagliptin improves diabetic kidney disease (DKD) by promoting mitochondrial biosynthesis via activating adenosine monophosphate activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α/mitochondrial transcription factor A (AMPK/PGC-1α/TFAM) pathway. With 6 male SD rats feeding normal chow as the control group, 16 SD rat models of DKD induced by intraperitoneal injection of 45 mg/kg STZ and high-fat and high-glucose feeding for 4 weeks were randomized into DKD model group and linagliptin treatment group. The rats in the latter two groups were subjected to daily intragastric administration of vehicle or 5 mg/kg linagliptin (dissolved in 5 g/L sodium carboxymethylcellulose, final concentration of 2 mg/mL) for 12 weeks with further high-fat and high-glucose feeding. After the treatments, the rats were sacrificed and blood samples from the abdominal aorta and kidney tissues were collected for testing blood glucose, liver function and lipid metabolism; HE, PAS, Masson, Sirius red staining and electron microscopy were used to observe renal tissue damage. Renal expressions of transforming growth factor β1 (TGF-β1), fibronectin (FN) and collagen I (Col I) were detected by immunohistochemistry, and the changes in membrane potential (ΔψM) and ATP enzyme content were analyzed to assess mitochondrial damage; The expressions of AMPK/PGC-1α/TFAM pathway proteins were detected using Western blotting. Compared with DKD model rats, the rats receiving linagliptin treatment showed significantly decreased blood glucose level (P < 0.01) and improved proteinuria (P < 0.05) with obviously alleviated renal ultrastructural damage and fibrosis, increased ATPase content and ΔψM (P < 0.0001), and enhanced renal expressions of P-AMPK/AMPK, PGC-1α and TFAM (P < 0.05). Linagliptin improves proteinuria and renal fibrosis in rat models of DKD possibly by activating the AMPK/PGC-1α/TFAM pathway to promote mitochondrial biosynthesis.

Genomic and biochemical analysis reveals fermented product of a putative novel Romboutsia species involves the glycometabolism of tilapia

Fish have a restricted capacity to utilize carbohydrates. Gut microbiota contribute to carbohydrate degradation in the host. The connection between the intestinal microbiota and carbohydrate metabolism is not well known in fish. We found that when feed was transformed from zooplankton-based to plant-based diet, the population of genus Romboutsia in tilapia gut increased. We inferred that the abundance of the genus Romboutsia was positively correlated with dietary sugar levels. Then, a strain of genus Romboutsia was obtained and designated MY01. Strain MY01 was a novel species of Romboutsia based on its genomic analysis. Many genes involved in carbohydrate metabolism were found in its genome, including Carbohydrate Active enZymes (CAZymes) genes associated with dietary fiber fermentation. An increased quantity of short-chain fatty acids (SCFAs) and decreased quantity of carbohydrates in feed fermented with MY01 were revealed by GC–MS and HPLC analysis. Fermented feed with MY01 increased the insulin content and decreased the glucose content of tilapia serum. Our in vivo and in vitro results are the first to suggest that fermented feed with Romboutsia regulates the tilapia glycometabolism by producing SCFAs to stimulate insulin secretion, and by reducing carbohydrates content of feed simultaneously to decrease blood glucose eventually. In further, the study provides a potential source of SCFAs production.

Mitigating iftar-related glycemic excursions in adolescents and young adults with type 1 diabetes on MiniMed™ 780G advanced hybrid closed loop system: a randomized clinical trial for adjunctive oral vildagliptin therapy during Ramadan fasting

BackgroundRamadan Iftar meal typically causes glucose excursions. Dipeptidyl peptidase-4 inhibitors increase glucagon-like peptide-1 and thus, decrease blood glucose levels with low risk of hypoglycemia.AimTo investigate the efficacy and safety of vildagliptin as an add-on therapy on glucose excursions of Iftar Ramadan meals among adolescents and young adults with type 1 diabetes mellitus (T1DM) using advanced hybrid closed-loop (AHCL) treatment.MethodsFifty T1DM patients on MiniMed™ 780G AHCL were randomly assigned either to receive vildagliptin (50 mg tablet) with iftar meal during Ramadan month or not. All participants received pre-meal insulin bolus based on insulin-to-carbohydrate ratio (ICR) for each meal constitution.ResultsVildagliptin offered blunting of post-meal glucose surges (mean difference − 30.3 mg/dL [− 1.7 mmol/L] versus − 2.9 mg/dL [− 0.2 mmol/L] in control group; p < 0.001) together with concomitant exceptional euglycemia with time in range (TIR) significantly increased at end of Ramadan in intervention group from 77.8 ± 9.6% to 84.7 ± 8.3% (p = 0.016) and time above range (180–250 mg/dL) decreased from 13.6 ± 5.1% to 9.7 ± 3.6% (p = 0.003) without increasing hypoglycemia. A significant reduction was observed in automated daily correction boluses and total bolus dose by 23.9% and 16.3% (p = 0.015 and p < 0.023, respectively) with less aggressive ICR settings within intervention group at end of Ramadan. Coefficient of variation was improved from 37.0 ± 9.4% to 31.8 ± 7.1%; p = 0.035). No severe hypoglycemia or diabetic ketoacidosis were reported.ConclusionAdjunctive vildagliptin treatment mitigated postprandial hyperglycemia compared with pre-meal bolus alone. Vildagliptin significantly increased TIR while reducing glycemic variability without compromising safety.Trial registration This trial was registered under ClinicalTrials.gov Identifier no. NCT06021119.

Effect of Diet Fortified with Okra Powder on Blood Quality in Broiler Chickens Under Heat Stress Conditions

An experiment was conducted in the poultry farm of the Department of Animal Resources-College of Agriculture - University of Kufa for the period from 10/10/2022 to 11/13/2022. The purpose of the study was to test the effect of adding okra fruits powder or seeds to the diet on some productive traits of broiler under Daily temperature stress conditions. 360 unsexed broiler chicks, Rose 308 hybrid, one day old, with an average weight of 37 g/chick were used. The chicks were fed on three diets that are from the age of 1 day-10 days, the second diet from the age of 11 days-24 days, and the third diet from the age of 25 days-35 days. The energy level of the three diets, respectively, was 3015, 3081, 3210 kcol / kg, and the protein level was 23.11, 21.51. 19.58 The one-day old chicks were randomly divided into 6 treatments with 4 replications 15 chicks each. The treatments were T1 the control (standard diet), T2 ration with okra seed powder 5 g/Kg feed, T3 was okra seed powder by 10 g/Kg feed, T4 was with okra fruit powder by 5 g/Kg feed, T5 was okra fruit powder at 10 g/Kg of feed, and T6 ration with 5 g seed powder + 5 g of fruit powder. The results showed that adding powdered okra fruits or seeds to the chicken diet affected blood quality. Compared with the control treatment, a significant increase in the concentration of the SOD enzyme was recorded in T6, T5, and T3 treatments, a significant decrease in the concentration of MAD enzyme in all treatments, and a significant decrease in the H/L cells ratio in the chicks of the two treatments T5 and T3 compared to the control T1, as the other treatments did not differ. Most of the treatments containing okra powder recorded a significant decrease in blood glucose especially for treatment T5, with a significant difference from all treatments that differed from T1. The blood content of total protein increased in the T6, T5, T4, and T3 treatments compared to the control T1 and T2. There was a significant decrease in the concentration of uric acid for all the treatments and a higher significant decrease in blood cholesterol for T6 chicks compared to the control.

Combination of ketogenic diet and probiotics inhibits breast cancer in mice by immune system modulation and reduction of Insulin growth factor-1

Breast cancer (BC) is the most prevalent malignancy in women and the first tumor type in the world. Ketogenic diets (KD), which are high in fat, low in carbohydrates, and sufficient in protein, can be used alone or as adjuvants with cancer drug medication as cancer therapy or prevention methods. Probiotics are nonpathogenic microorganisms or groups of bacteria that live in the gut and nourish the host body. In this work, we tested a new KD-probiotic combination against breast cancer implanted in mice. Several combination of probiotics (1×109 CFU/0.5ml) and KD (14.1 kcal/2g) reduced tumor size and enhanced cure rate. KD and combination therapy groups increased beta-hydroxybutyrate (β-OHB) while decrease blood glucose, and IGF-1.IFN-γ, IL-2, IL-4, and IL-10 serum levels were measured to assess immune reaction to various therapies. Combination and probiotics therapy raised IFN-γ, and IL-4 levels, however IL-10 level did decrease in all treated group with highest decrease in combination group. In the safety profile, probiotics, ketogenic diet, and their combination were safe. Overall, the combination of a ketogenic diet and probiotics has the potential to be utilized in the future development of anti-cancer nutrition to augment conventional therapies. Graphical abstract. Summary of the effect of Ketogenic diet, Probiotics and its combination on EMP-6 breast cancer cell and in vivo:

Study of the influence of GLP-1 receptor agonists on the metabolic activity of the intestinal microbiota in patients with type 2 DM

The aim: to investigate the peculiarities of the metabolic activity of the intestinal microbiota in patients with type 2 diabetes under the influence of glucagon-like peptide-1 receptor agonist therapy. Materials and methods: 21 patients with type 2 diabetes mellitus were included in the study, the average age was 57.2±8.53 years (M±SD), the HbA1c level was 8.29±0.88 % (M±SD). Patients were prescribed raGLP-1 at the maximum tolerated dose for 6 months. Before and after the course of treatment, indicators of body composition were determined by the bioelectrical impedance method (TANITA BC-545N analyzer, Japan), characteristics of carbohydrate metabolism and the lipid spectrum of blood serum, as well as the concentration of GLP-1, trimethylamine-N-oxide (TMAO) by the immunoenzymatic method, of short-chain fatty acids (SCFA) by the method of chromatographic research. Results. After 6 months of therapy with liraglutide against the background of a statistically significant decrease in fasting blood glucose and HbA1c levels (p&lt;0.05), a decrease in body mass index and waist circumference (p&lt;0.05), a decrease in the content of visceral (p&lt;0.05 ) and total fat (p&lt;0.05) in patients with type 2 diabetes, there was a decrease in the concentration of TMAO in blood serum (p&lt;0.05) and an increase in the concentration of SCFA: acetic, propionic (p&lt;0.05) in the coprofiltrate and a tendency to increase in the level of butyric acids. Data analysis also established an increase in the concentration of endogenous GLP-1 in the blood (p&lt;0.05). Conclusions. The detected changes in microbial metabolites may indicate a positive effect of raGLP-1 on the composition of the intestinal microbiota and its metabolic activity in patients with T2DM, which in turn contributes to the improvement of endogenous secretion of incretins

Beyond Glycemic Control: Mechanistic Insights Into SGLT-2 Inhibitors in Heart Failure Management.

Heart failure is a common and clinically significant cardiac condition that causes significant morbidity and mortality in the United States. Diabetes and hypertension are 2 of the most common comorbidities associated with heart failure. Other risk factors for heart failure include smoking, obesity, and intrinsic cardiac diseases such as myocardial infarction and valvular pathologies. All of these conditions, to some extent, cause remodeling within the cardiomyocyte, which eventually leads to the development of congestive heart failure. Over the years, using diuretics and medications that inhibit the Renin-Angiotensin-Aldosterone System has been the traditional treatment for congestive heart failure. But in recent years studies in the diabetic population revealed that sodium-glucose cotransporter-2 inhibitors had a negative impact on the remodeling of cardiomyocytes. In this review, we discuss the numerous molecular mechanisms by which these recently developed medicines inhibit remodeling in cardiomyocytes, independent of their intended effect of decreasing blood glucose levels. Furthermore, it emphasizes the use of these drugs in diabetic as well as non-diabetic patients as a promising adjunct to ongoing heart failure treatment.

DHA promotes healthy adipose tissue remodeling and carbohydrate utilization in grass carp (Ctenopharyngodon idellus) and largemouth bass (Micropterus salmoides)

Due to the wide usage of high-carbohydrate diets in aquaculture, improving the ability of fish to utilize high-carbohydrate diets is one of the important issues in aquaculture. Adipose tissue is an essential organ for storing energy and plays a vital role in glucose homeostasis. In this study, RNA sequencing reveals that docosahexaenoic acid (DHA) promoted the expression of the glucose metabolism related-genes in grass carp adipocytes, raising the hypothesis that DHA may attenuate the adverse effect of high-carbohydrate diets on fish via promoting glucose metabolism in adipose tissue. To verify this hypothesis, a total of 180 juvenile grass carp (14.24 ± 0.43 g) and a total of 180 largemouth bass (40.03 ± 0.12 g) were randomly distributed into 18 tanks (200 L), respectively, and fed with high-carbohydrate diets containing DHA. The results showed that high-carbohydrate diets promoted glycolysis and inhibited lipolysis and fatty acid β-oxidation, leading to the excessive accumulation of abdominal fat and adipose tissue inflammation. After feeding high-carbohydrate diets supplementation with DHA, glucose transporter type 4 (GLUT4) mediated-glucose uptake was increased in adipose tissue, resulting in significantly decreased blood glucose in grass carp and largemouth bass (P < 0.05). And then, the glucose was converted to triglyceride through the glucose-6-phosphate dehydrogenase (G6PD) mediated-pentose phosphate pathway, de novo synthesis of fatty acids and triglyceride (TG) synthesis. Subsequently, the resulting TG was broken down through lipolysis and fatty acid β-oxidation. These reprogrammed metabolic processes inhibited the excessive accumulation of abdominal fat. In addition, DHA attenuated inflammation in adipose tissue, and further reduced the levels of inflammatory cytokines in serum (P < 0.05), indicating that DHA promotes healthy adipose tissue remodeling. Ultimately, these benefits improved the growth performance of grass carp and largemouth bass fed with high-carbohydrate diets. Taken together, our study indicates that adipose tissue is an important target for improving the negative effects of high-carbohydrate diets, and DHA could promote healthy adipose tissue remodeling and improve carbohydrate utilization in fish by reprogramming the glucose and lipid metabolism in adipose tissues.

Effectiveness of rosuvastatin and pulmonary rehabilitation in patients with concurrent course of asthma, chronic obstructive pulmonary disease and diabetes mellitus type 2

The aim of this study was to assess the effectiveness of rosuvastatin and pulmonary rehabilitation in patients with asthma-COPD overlap (ACO) concurrent with type 2 diabetes (T2D).Material and methods. A total of 26 patients with ACO and T2D were examined, with an average age of 61 [55.6; 67.8]. In addition to standard therapy, patients in the main group were prescribed rosuvastatin and a pulmonary rehabilitation program. Treatment efficacy was assessed using questionnaires (CAT, ACQ, SGRQ), dyspnea severity scale (mMRC), BODE index, pulmonary function, bioimpedance analysis, 6-minute walk test, carbohydrate and lipid metabolism status, levels of 8-isoprostane, sCD14, CRP, stable nitric oxide (NO) metabolites - nitrite and nitrate ions, and endothelin-1 in the blood. Results. In the main group, a significant improvement was observed during the treatment course, including a 40% reduction in the BODE index (p&lt;0.05), a 33.4% decrease in dyspnea on the mMRC scale (p&lt;0.05), a 28.5% reduction in CAT, a 40.8% decrease in ACQ, and a 20.6% decrease in SGRQ. Other notable improvements included a 1.3% decrease in BMI, a 13% reduction in body fat percentage, a 23.5% decrease in visceral fat level, a 16% increase in patients' tolerance to physical activity, a 27.5% increase in FEV1 (p&lt;0.05), an 8.1% decrease in fasting blood glucose (p&lt;0.01), a 20% reduction in triglycerides (p&lt;0.05), a 24.9% decrease in LDL cholesterol, and a 27.2% decrease in total cholesterol (p&lt;0.05). Additionally, there was a 23.8% decrease in CRP levels (p&lt;0.05), a two-fold reduction in blood 8-isoprostane levels (p&lt;0.05), a 58% reduction in serum sCD14 levels, a 59.8% increase in stable nitric oxide metabolites (p&lt;0.05), and a 55% decrease in endothelin-1 levels (p&lt;0.05).Conclusions. The use of rosuvastatin and pulmonary rehabilitation significantly improves the quality of life for patients with the concurrent presentation of COPD, asthma, and T2D. It reduces the severity of dyspnea, enhances tolerance to physical activity, improves pulmonary function, lowers visceral fat levels and body fat percentage, enhances lipid profile, and improves endothelial function, all while concurrently reducing oxidative stress and systemic inflammation without worsening carbohydrate metabolism.

The selective NOX4 inhibitor GLX7013159 decreases blood glucose concentrations and human beta-cell apoptotic rates in diabetic NMRI nu/nu mice transplanted with human islets

NADPH oxidase 4 (NOX4) inhibition has been reported to mitigate diabetes-induced beta-cell dysfunction and improve survival in vitro, as well as counteract high-fat diet-induced glucose intolerance in mice. We investigated the antidiabetic effects of the selective NOX4 inhibitor GLX7013159 in vivo in athymic diabetic mice transplanted with human islets over a period of 4 weeks. The GLX7013159-treated mice achieved lower blood glucose and water consumption throughout the treatment period. Furthermore, GLX7013159 treatment resulted in improved insulin and c-peptide levels, better insulin secretion capacity, as well as in greatly reduced apoptotic rates of the insulin-positive human cells, measured as colocalization of insulin and cleaved caspase-3. We conclude that the antidiabetic effects of NOX4 inhibition by GLX7013159 are observed also during a prolonged study period in vivo and are likely to be due to an improved survival and function of the human beta-cells.

Agaricus Subrufescens ameliorates ovarian dysfunction and regulates altered biochemical parameters in rats with Letrozole induced polycystic ovarian syndrome

ObjectiveThe objective of this study is to investigate the effects of an ethanolic extract derived from Agaricus subrufescens on rat models exhibiting Polycystic Ovarian Syndrome (PCOS) induced by Letrozole.MethodsA total of thirty female Wistar rats were divided into five groups, each consisting of six rats. The negative control group was administered a volume of 1 mL of a 0.5% solution of carboxy methylcellulose (CMC). Letrozole (1 mg/kg) was administered to additional groups for a duration of 21 days in order to induce polycystic ovary syndrome (PCOS). Animals designated as positive controls were euthanized on the 22nd day. Both the test group and the standard group were subjected to treatment from the 22nd day to the 36th day. The experimental group was administered ethanolic extract of Agaricus subrufescens at doses of 200 mg/kg and 400 mg/kg p.o, while the control group received clomiphene citrate at a dose of 1 mg/kg. The study observed various physiological markers in individuals with polycystic ovarian disease, including estimated blood glucose levels, total cholesterol levels, triglyceride levels, and hormonal fluctuations such as increased testosterone and estrogen levels, as well as decreased progesterone levels. The presence of menstrual irregularities was confirmed through the examination of vaginal smears and histopathological changes in the ovaries.ResultsThe consumption of Agaricus subrufescens was found to have a significant impact on various physiological parameters, including blood glucose levels, testosterone levels, anovulation, and menstrual irregularity. All therapeutic interventions significantly normalized the levels of serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT). The rats with polycystic ovary syndrome (PCOS) that were induced by Letrozole exhibited increased levels of urea and creatinine. The findings of this study indicate that the administration of Agaricus subrufescens therapy has a protective effect on renal function, as evidenced by a reduction in serum levels of urea and creatinine. In rats with polycystic ovary syndrome (PCOS) induced by Letrozole, the inhibition of hepatic synthesis, promotion of ovarian follicle immaturity, and elevation of androgen secretions result in an increase in the weight of the liver and ovaries. The weight of endocrine organs exhibited a decrease across all treatment groups. The histopathological examination of PCOS specimens revealed an increased presence of cysts and theca lutein cells. The group of rats with polycystic ovary syndrome (PCOS) that did not receive treatment exhibited a higher number of cysts compared to the groups that received treatment.ConclusionThis study demonstrated that the administration of Letrozole orally resulted in the development of polycystic ovarian disease. The results indicated heightened levels of blood glucose, total cholesterol, and triglycerides, as well as alterations in hormone levels such as increased testosterone and estrogen, and decreased progesterone. These hormonal changes were accompanied by menstrual irregularities, which were confirmed through the examination of vaginal smears and histopathological analysis of the ovaries in the control group with polycystic ovarian disease. The treatment groups that received Agaricus subrufescens exhibited a decrease in blood glucose, total cholesterol, and testosterone levels.

Canagliflozin ameliorates hypobaric hypoxia-induced pulmonary arterial hypertension by inhibiting pulmonary arterial smooth muscle cell proliferation

ABSTRACT Pulmonary arterial hypertension (PAH) is a disease with a high mortality and few treatment options to prevent the development of pulmonary vessel remodeling, pulmonary vascular resistance, and right ventricular failure. Canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is originally used in diabetes patients which could assist the glucose excretion and decrease blood glucose. Recently, a few studies have reported the protective effect of SGLT2 inhibitor on monocrotaline-induced PAH. However, the effects of canagliflozin on hypobaric hypoxia-induced PAH as well as its mechanism still unclear. In this study, we used hypobaric hypoxia-induced PAH mice model to demonstrate if canagliflozin could alleviate PAH and prevent pulmonary vessel remodeling. We found that daily canagliflozin administration significantly improved survival in mice with hypobaric hypoxia-induced PAH compared to vehicle control. Canagliflozin treatment significantly reduced right ventricular systolic pressure and increased pulmonary acceleration time determined by hemodynamic assessments. Canagliflozin significantly reduced medial wall thickening and decreased muscularization of pulmonary arterioles compared to vehicle treated mice. In addition, canagliflozin inhibited the proliferation and migration of pulmonary arterial smooth muscle cells through suppressing glycolysis and reactivating AMP-activated protein kinase signaling pathway under hypoxia condition. In summary, our findings suggest that canagliflozin is sufficient to inhibit pulmonary arterial remodeling which is a potential therapeutic strategy for PAH treatment.

Serum biochemical parameters of Yankasa sheep experimentally infected with &lt;i&gt;Trypanosoma evansi&lt;/i&gt; and treated with diminazene aceturate (Berenil®)

Blood glucose, serum total protein, and liver transaminases were determined in Yankasa sheep experimentally infected with Trypanosoma evansi (T. evansi) and treated with diminazene aceturate (Berenil® ). A total of 30 animals were divided into 6 groups (A to F) (n=5). Animals from each group were either uninfected or infected with T. evansi and treated with Berenil® . Infection of the infected groups (A, C and E) was done via intravenous inoculation of T. evansi, while the infected group C and E were treated with Berenil® at 3.5 and 7 mg/kg BW (single dose), respectively, by day 16 post-infection (PI). The infected groups had a pre-patent period of 8 days, with similar levels of parasitaemia of 4.7 ± 0.27. In group A, the mean parasite count rose significantly (p &lt; 0.05) to 72.8 ± 1.07 by day 12 PI and continued to a peak value of 250.6 ± 1.98 by day 28 PI. In groups C and E, the initial parasitaemia rose significantly (p &lt; 0.05) to a peak count of 80.8 ± 1.12 and 78.2 ± 1.11 by day 12 PI, following treatment with 3.5 and 7.0 mg/kg BW of Berenil® , by day 20 PI, respectively, and was completely eliminated by day 9 and 5 post-treatment (PT), respectively. The biochemical analysis showed that, from day 8 PI, the infected sheep experienced significant (p &lt; 0.05) increases in alkaline phosphatase, aspartate and alanine aminotransferase, creatinine and urea; with decreases in blood glucose and total protein. However, these changes reverted to their pre-infection values, by day 28 PI in all the affected animals following treatment with both doses of Berenil® . It is therefore, concluded that the two doses of Berenil® (3.5 mg/kg and 7.0 mg/kg) were effective in the treatment of the disease but 7.0 mg/kg cleared the parasitaemia faster.

Rubia cordifolia L. Attenuates Diabetic Neuropathy by Inhibiting Apoptosis and Oxidative Stress in Rats.

Diabetic neuropathy is a debilitating manifestation of long-term diabetes mellitus. The present study explored the effects of the roots of Rubia cordifolia L. (R. cordifolia L.) in the Wistar rat model for diabetic neuropathy and possible neuroprotective, antidiabetic, and analgesic mechanisms underlying this effect. Rats were divided into five experimental groups. An amount of 0.25% carboxy methyl cellulose (CMC) in saline and streptozotocin (STZ) (60 mg/kg) was given to group 1 and group 2, respectively. Group 3 was treated with STZ and glibenclamide simultaneously while groups 4 and 5 were simultaneously treated with STZ and hydroalcoholic extract of the root of R. cordifolia, respectively. Hot plate and cold allodynias were used to evaluate the pain threshold. The antioxidant effects of R. cordifolia were assessed by measuring Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). At the end of the study, sciatic nerve and brain tissues were collected for histopathological study. Bcl-2 proteins, cleaved caspase-3, and Bax were assessed through the Western blot method. R. cordifolia significantly attenuated paw withdrawal and tail flick latency in diabetic neuropathic rats. R. cordifolia significantly (p < 0.01) improved the levels of oxidative stress. It was found to decrease blood glucose levels and to increase animal weight in R. cordifolia-treated groups. Treatment with R. cordifolia suppressed the cleaved caspase-3 and reduced the Bax:Bcl2 ratio in sciatic nerve and brain tissue compared to the diabetic group. Histopathological analysis also revealed a marked improvement in architecture and loss of axons in brain and sciatic nerve tissues at a higher dose of R. cordifolia (400 mg/kg). R. cordifolia attenuated diabetic neuropathy through its antidiabetic and analgesic properties by ameliorating apoptosis and oxidative stress.

SCH772984 ameliorates lipopolysaccharide-induced hypoglycemia in mice through reversing MEK/ERK/Foxo1-mediated gluconeogenesis suppression.

Lipopolysaccharide (LPS) results in a lethal hypoglycemic response. However, the main molecular mechanism involved in LPS-induced glucose metabolism disorder is poorly understood. This study intends to investigate the signaling pathways involved in LPS-induced hypoglycemia and potential efficacy of extracellular signal-regulated kinase (ERK) inhibitor SCH772984. The effects of LPS and SCH772984 on gluconeogenesis, glucose absorption, and glycogenolysis were evaluated by pyruvate tolerance test, oral glucose tolerance test, and glucagon test, respectively. After a single intraperitoneal injection of 0.5mg/kg LPS, the mice's blood glucose levels and gluconeogenesis ability were significantly lower than that of control group. Besides, mRNA and protein expression of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) decreased significantly after LPS treatment. LPS induced the phosphorylation of ERK1/2, MEK1/2 (mitogen-activated protein kinase), and Foxo1 while inhibited Foxo1 expression in the nucleus, indicating an important role of the MEK/ERK/Foxo1 signaling in the inhibition of gluconeogenesis by LPS. Furthermore, SCH772984 elevated blood glucose, increased the G6Pase and PEPCK expression, and inhibited pERK1/2 and pFoxo1 expression in LPS-induced mice. In summary, LPS inhibited gluconeogenesis and induced hypoglycemia through the MEK/ERK/Foxo1 signal pathway, and ERK inhibitor could effectively reverse decreased blood glucose in mice with LPS treatment. These findings provide a novel therapeutic target for LPS-induced hypoglycemia.

Arginine and Lysine Supplementation Potentiates the Beneficial β-Hydroxy ß-Methyl Butyrate (HMB) Effects on Skeletal Muscle in a Rat Model of Diabetes.

Skeletal muscle is the key tissue for maintaining protein and glucose homeostasis, having a profound impact on the development of diabetes. Diabetes causes deleterious changes in terms of loss of muscle mass, which will contribute to reduced glucose uptake and therefore progression of the disease. Nutritional approaches in diabetes have been directed to increase muscle glucose uptake, and improving protein turnover has been at least partially an oversight. In muscle, β-hydroxy β-methyl butyrate (HMB) promotes net protein synthesis, while arginine and lysine increase glucose uptake, albeit their effects on promoting protein synthesis are limited. This study evaluates if the combination of HMB, lysine, and arginine could prevent the loss of muscle mass and function, reducing the progression of diabetes. Therefore, the combination of these ingredients was tested in vitro and in vivo. In muscle cell cultures, the supplementation enhances glucose uptake and net protein synthesis due to an increase in the amount of GLUT4 transporter and stimulation of the insulin-dependent signaling pathway involving IRS-1 and Akt. In vivo, using a rat model of diabetes, the supplementation increases lean body mass and insulin sensitivity and decreases blood glucose and serum glycosylated hemoglobin. In treated animals, an increase in GLUT4, creatine kinase, and Akt phosphorylation was detected, demonstrating the synergic effects of the three ingredients. Our findings showed that nutritional formulations based on the combination of HMB, lysine, and arginine are effective, not only to control blood glucose levels but also to prevent skeletal muscle atrophy associated with the progression of diabetes.

The Effect of Curcumin on Blood Glucose Patients with Type 2 Diabetes Mellitus: A Systematic Review

Type 2 Diabetes Mellitus (DM) is characterized by elevated blood glucose. Curcumin has glucose-lowering properties. This review intended to determine if Curcumin can lower blood glucose levels in type 2 diabetic patients. This review intended to determine if Curcumin can decrease blood glucose in type 2 DM patients. Curcumin has a mechanism of stimulating incretin and inhibiting digestive enzymes from reducing blood glucose levels in type 2 DM patients. We systematically searched PubMed for peer-reviewed studies examining the mechanism of Curcumin in decreasing blood glucose in type 2 DM patients. The journal criteria included in this review were a study from 2000 to 2022, randomized control trial using intervention Curcumin, an outcome variable using blood glucose, the full text of the article can be obtained, and the DM patient's age is over 18 years. Two independent reviewers retrieved data o clinical outcomes, studies, and patient characteristics using the Cochrane Risk of Bias Assessment Instrument. Quality is evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. There are 19 studies included in this research, and Three journals meet the requirements. The conclusion is that curcumin can decrease blood glucose in Type 2 DM patients.

Pengaruh Pemberian Seduhan Teh Hijau (Camellia Sinensis) Terhadap Kadar Glukosa Darah dan Malondialdehide (MDA)

Oxidative stress is a condition where there is an imbalance between oxidants and antioxidants in the body which can trigger psychological stress. Oxidative stress can be reduced by consuming exogenous antioxidants (antioxidants from outside), where green tea is thought to be able to reduce oxidative stress. The aim of this study was to examine the effect of steeping green tea on blood glucose and Malondialdehyde (MDA) levels in male Wistar Strain white rats exposed to psychological stress. The design used in this research was Randomized Post Test Only Group Design. There were 5 groups of mice; 2 are a normal control group and a stress control group, and 3 treatment groups. Previously, the mice were given psychological stress 1 x 24 hours in the form of disturbed sleep patterns, so that the experimental animals experienced oxidative stress, then green tea was given to the treatment group with a single dose of 3.6 ml/head in the 1st hour in the group. treatment 1, 6th hour in treatment group 2, and 24th hour in treatment group 3. Statistical analysis used the Manova test. Based on statistical analysis, it shows that there was a decrease in blood glucose and Malondialdehyde (MDA) levels in all treatment groups given exposure to psychological stress and steeping green tea. A single dose of green tea brewing in experimental animals experiencing oxidative stress was proven to be able to neutralize oxidative stress in the 1st hour after administration of green tea brewing and the antioxidant activity still lasted up to 24 hours.

Biodistribution of Intravenously Transplanted Mitochondria Conjugated with Graphene Quantum Dots in Diabetic Rats.

Mitochondria transplantation has emerged as a successful therapeutic modality to treat several degenerative diseases. However, the biodistribution of transplanted mitochondria has not been well studied. We investigated the ex-vivo systemic biodistribution and therapeutic efficacy of intravenously transplanted graphene quantum dots (GQDs) conjugated to isolated mitochondria (Mt-GQDs) in diabetic rat tissues. The results revealed that Mt-GQDs facilitate the tracking of transplanted mitochondria without affecting their therapeutic efficacy. It is compelling to note that Mt-GQDs and isolated mitochondria show comparable therapeutic efficacies in decreasing blood glucose levels, oxidative stress, inflammatory gene expressions, and restoration of different mitochondrial functions in pancreatic tissues of diabetic rats. In addition, histological section examination under a fluorescence microscope demonstrated the localization of Mt-GQDs in multiple tissues of diabetic rats. In conclusion, this study indicates that Mt-GQDs provide an effective mitochondrial transplantation tracking modality.

Antidiabetic and Liver Tissue Improvement Potency of Surf Redfish (Actinopyga mauritiana) in Alloxan-Induced Diabetic Mice

Long-term hyperglycemia is associated with various organ damage. One of these damages is Non-Alcoholic Fatty Liver Disease (NAFLD). One of the potential natural products that may improve this impact is Surf Redfish. Hence this study aimed to investigate the antidiabetic and liver protection effects of Surf Redfish in some diabetic male Mice. This study was an experimental study that used 25 male mice grouped into control, standard, Surf Redfish Extract-I (100 mg/ kg BW), II (200 mg// kg BW), and III (400 mg/ kg BW). This study evaluated the blood glucose level (before and after induction, third, sixth, ninth, twelfth, and fifteenth days) and histology study of liver tissue. This study showed that the Surf Redfish ethanol extract significantly decreased blood glucose levels every day for fifteen days (P-Value &lt; 0.05). This extract also showed a significant decrease in vacuolated degeneration after fifteen days of extract administration (P-Value). Hence, it can be concluded that the most effective dose of Surf Redfish extracts in this study was 400 mg/ kg BW to decrease blood glucose level and width of vacuolated degeneration after fifteen days of administration.