scholarly journals Antioxidant Effects and Mechanisms of Medicinal Plants and Their Bioactive Compounds for the Prevention and Treatment of Type 2 Diabetes: An Updated Review

2020 ◽  
Vol 2020 ◽  
pp. 1-36 ◽  
Author(s):  
Jeremiah Oshiomame Unuofin ◽  
Sogolo Lucky Lebelo
Keyword(s):  
Side Effects ◽  
Beta Cell ◽  
Cell Function ◽  
Bioactive Molecules ◽  
Endocrine Gland ◽  
Glucose Levels ◽  
Cell Dysfunction ◽  
Blood Glucose Levels ◽  
Lower Blood ◽  
Glucagon Like Peptide 1

Diabetes mellitus is a metabolic disorder that majorly affects the endocrine gland, and it is symbolized by hyperglycemia and glucose intolerance owing to deficient insulin secretory responses and beta cell dysfunction. This ailment affects as many as 451 million people worldwide, and it is also one of the leading causes of death. In spite of the immense advances made in the development of orthodox antidiabetic drugs, these drugs are often considered not successful for the management and treatment of T2DM due to the myriad side effects associated with them. Thus, the exploration of medicinal herbs and natural products as therapeutic sources for the treatment of T2DM is promoted because they have little or no side effects. Bioactive molecules isolated from natural sources have been proven to lower blood glucose levels via regulating one or more of the following mechanisms: improvement of beta cell function, insulin resistance, glucose (re)absorption, and glucagon-like peptide-1 homeostasis. In recent times, the mechanisms of action of different bioactive molecules with antidiabetic properties and phytochemistry are gaining a lot of attention in the area of drug discovery. This review article presents an update of the findings from clinical research into medicinal plant therapy for T2DM.

scholarly journals Changes induced by sucrose administration on glucose metabolism in pancreatic islets in normal hamsters

2001 ◽  
Vol 171 (3) ◽  
pp. 551-556 ◽  
Author(s):  
ML Massa ◽  
MI Borelli ◽  
H Del Zotto ◽  
JJ Gagliardino
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Glucose Metabolism ◽  
Beta Cell ◽  
Cell Function ◽  
Normal Male ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Glucose Phosphorylation

We correlated the changes in glucose-induced insulin secretion with those observed in glucose metabolism and hexokinase/glucokinase activity in islets from normal sucrose-fed hamsters. Blood glucose and insulin levels were measured in normal male hamsters fed with (S5) or without (C5) 10% sucrose in the drinking water for 5 weeks. Isolated islets (collagenase digestion) from both groups of animals were used to study insulin secretion, (14)CO(2) and (3)H(2)O production from D-[U-(14)C]-glucose and D-[5-(3)H]-glucose respectively, with 3.3 or 16.7 mM glucose in the medium, and hexokinase/glucokinase activity (fluorometric assay) in islet homogenates. Whereas S5 and C5 animals had comparable normal blood glucose levels, S5 showed higher insulin levels than C5 hamsters (2.3+/-0.1 vs 0.6+/-0.03 ng/ml, P<0.001). Islets from S5 hamsters released significantly more insulin than C5 islets in the presence of low and high glucose (3.3 mM glucose: 0.77+/-0.04 vs 0.20+/-0.06 pg/ng DNA/min, P<0.001; 16.7 mM glucose: 2.77+/-0.12 vs 0.85+/-0.06 pg/ng DNA/min, P<0.001) and produced significantly higher amounts of (14)CO(2) and (3)H(2)O at both glucose concentrations ((14)CO(2): 3.3 mM glucose: 0.27+/-0.01 vs 0.18+/-0.01, P<0.001; 16.7 mM glucose: 1.44+/-0.15 vs 0.96+/-0.08, P<0.02; (3)H(2)O: 3.3 mM glucose: 0.31+/-0.02 vs 0.15+/-0.01, P<0.001; 16.7 mM glucose: 1.46+/-0.20 vs 0.76+/-0.05 pmol glucose/ng DNA/min, P<0.005). The hexokinase K(m) and V(max) values from S5 animals were significantly higher than those from C5 ones (K(m): 100.14+/-7.01 vs 59.90+/- 3.95 microM, P<0.001; V(max): 0.010+/-0.0005 vs 0.008+/- 0.0006 pmol glucose/ng DNA/min, P<0.02). Conversely, the glucokinase K(m) value from S5 animals was significantly lower than in C5 animals (K(m): 15.31+/-2.64 vs 35.01+/-1.65 mM, P<0.001), whereas V(max) figures were within a comparable range in both groups (V(max): 0.048+/-0.009 vs 0.094+/-0.035 pmol glucose/ng DNA/min, not significant). The glucose phosphorylation ratio measured at 1 and 100 mM (hexokinase/glucokinase ratio) was significantly higher in S5 (0.26+/-0.02) than in C5 animals (0.11+/-0.01, P<0.005), and it was attributable to an increase in the hexokinase activity in S5 animals. In conclusion, sucrose administration increased the hexokinase/glucokinase activity ratio in the islets, which would condition the increase in glucose metabolism by beta-cells, and in beta-cell sensitivity and responsiveness to glucose. These results support the concept that increased hexokinase rather than glucokinase activity causes the beta-cell hypersensitivity to glucose, hexokinase being metabolically more active than glucokinase to up-regulate beta-cell function.

scholarly journals Diabetic Ketoacidosis and Dysregulation of Proglucagon Family of Molecules

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 857-857
Author(s):  
Natia Peradze ◽  
Stanley Heydrick ◽  
Andrew Cole ◽  
Ari Moskowitz ◽  
Michael Donnino ◽  
...  
Keyword(s):  
Diabetic Ketoacidosis ◽  
Cell Function ◽  
Statistical Significance ◽  
Glucagon Secretion ◽  
Therapeutic Interventions ◽  
Healthy Controls ◽  
C Peptide ◽  
Glucose Levels ◽  
Cell Dysfunction ◽  
Glucagon Like Peptide 1

Abstract Objectives An increasing body of evidence supports a significant contributory role for pancreatic α-cell dysfunction in the pathophysiology of diabetic ketoacidosis (DKA). In normal physiology, high glucose levels stimulate insulin and inhibit glucagon secretion, while low glucose stimulates glucagon but inhibits insulin release. This regulatory mechanism is progressively lost in diabetes mellitus (DM), where diminished insulin levels are accompanied by hyperglucagonemia leading to the further aggravation of hyperglycemia caused by insulin deficiency. Glucagon is produced via the posttranslational modification of proglucagon in a process that also produces other proglucagon molecules including major proglucagon fragment (MPGF) and glucagon like peptide-1 (GLP-1). Here we hypothesized that DKA is associated with α-cell dysfunction leading to elevated levels of proglucagon molecules. Methods We measured levels of glucagon, GLP-1 and MPGF as indices of glucagon synthesis/α-cell function in the plasma of patients with DKA and in healthy controls. The inclusion criteria for DKA patients were glucose &gt; 250 mg/dL, pH &lt; 7.2, bicarbonate &lt; 15mEq/L, presence of ketones and patients were part of a larger randomized trial. Samples were obtained at baseline prior to trial interventions. An independent sample t-test was used to compare differences. Results We analyzed samples of 25 healthy controls and 59 individuals with DKA (47 T1DM and 12 T2DM) and found significant increase in glucagon levels in all of the DKA groups (controls 47 pg/mL (36, 67), T1DM 63 (40,135), T2DM 84 (61,105), p = 0.013). The differences were significant in MPGF too (controls 0.5 ng/mL (0.4, 0.8), T1DM 1.1 (0.7, 1.9), T2DM 1.3 (0.9, 2.0), p &lt; 0.001), while differences in GLP-1 between groups did not reach statistical significance. C-peptide levels were significantly diminished in DKA and the levels of glucagon and C-peptide were strongly associated in healthy controls but not in DKA. Conclusions Our data indicate that proglucagon family molecules may be actively contributing to the pathogenesis of DKA and may represent a potential site for future therapeutic interventions. Funding Sources The parental study of “Thiamine as adjunctive therapy for diabetic ketoacidosis” was supported through a grant from the National Institute of Health.

scholarly journals Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling

2020 ◽  
Vol 21 (24) ◽  
pp. 9444
Author(s):  
Hideaki Kaneto ◽  
Atsushi Obata ◽  
Tomohiko Kimura ◽  
Masashi Shimoda ◽  
Junpei Sanada ◽  
...  
Keyword(s):  
Cell Function ◽  
Early Stage ◽  
Receptor Expression ◽  
Protective Effects ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Levels ◽  
Cell Dysfunction ◽  
Blood Glucose Levels ◽  
Β Cell Function

Under healthy conditions, pancreatic β-cells produce and secrete the insulin hormone in response to blood glucose levels. Under diabetic conditions, however, β-cells are compelled to continuously secrete larger amounts of insulin to reduce blood glucose levels, and thereby, the β-cell function is debilitated in the long run. In the diabetic state, expression levels of insulin gene transcription factors and incretin receptors are downregulated, which we think is closely associated with β-cell failure. These data also suggest that it would be better to use incretin-based drugs at an early stage of diabetes when incretin receptor expression is preserved. Indeed, it was shown that incretin-based drugs exerted more protective effects on β-cells at an early stage. Furthermore, it was shown recently that endothelial cell dysfunction was also associated with pancreatic β-cell dysfunction. After ablation of insulin signaling in endothelial cells, the β-cell function and mass were substantially reduced, which was also accompanied by reduced expression of insulin gene transcription factors and incretin receptors in β-cells. On the other hand, it has been drawing much attention that incretin plays a protective role against the development of atherosclerosis. Many basic and clinical data have underscored the importance of incretin in arteries. Furthermore, it was shown recently that incretin receptor expression was downregulated in arteries under diabetic conditions, which likely diminishes the protective effects of incretin against atherosclerosis. Furthermore, a series of large-scale clinical trials (SPAED-A, SPIKE, LEADER, SUSTAIN-6, REWIND, PIONEER trials) have shown that various incretin-related drugs have beneficial effects against atherosclerosis and subsequent cardiovascular events. These data strengthen the hypothesis that incretin plays an important role in the arteries of humans, as well as rodents.

Antidiabetic effect of Psychotria malayana Jack in induced type 1 diabetic rat

MEDISAINS ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 19
Author(s):  
Fairuz Fairuz ◽  
Hasna Dewi ◽  
Humaryanto Humaryanto
Keyword(s):  
Blood Glucose ◽  
Side Effects ◽  
Type I Diabetes ◽  
Langerhans Cell ◽  
Diabetic Rat ◽  
Type I ◽  
Antidiabetic Effect ◽  
Glucose Levels ◽  
Blood Glucose Levels

Background: Therapies for hyperglycemic treatment, including insulin and oral diabetes medications, have been confirmed to cause several side effects. Thus, finding new drugs with fewer side effects is of high importance. Salung leaf herb (Psychotria malayana Jack) reported used in traditional societies as a treatment for diabetes. However, the scientific proof of this plant for diabetes treatment is still lacking.Objective: To evaluate the antidiabetic effect of the P. malayana jack in induced type 1 diabetic rats by assessing blood glucose level and pancreatic cells in white rats.Methods: Alloxan used to induce type I diabetes. Rats randomly divided into six groups. A Group P1 received 250 mg/kg BW; group P2 received 500 mg/kg BW, group P3 received 1000 mg/kg BW. While group 4 basal received no treatment, group 5 received distilled water as a negative control, and group 6 received glibenclamide as a positive control. Medications are given for six days. Glucose levels were measured, and observation of pancreatic Langerhans cell damages.Results:  A decrease in blood glucose levels observed in all treatment groups. The most significant reduction (49.76%; 1000 mg/kg BW) occurred in the P3 group. Morphological features of pancreatic Langerhans cell damage were slightly high in the P1 group.Conclusion: P. malayana Jack can consider having an antidiabetic effect in a type 1 diabetic rat by reducing blood glucose levels.

A GLP-1 Receptor Agonist Inhibits Aldosterone Release in Healthy Volunteers

2021 ◽  
Vol 53 (06) ◽  
pp. 402-407
Author(s):  
Tuuli Sedman ◽  
Vallo Volke ◽  
Keiu Heinla ◽  
Eero Vasar
Keyword(s):  
Healthy Volunteers ◽  
Ambulatory Setting ◽  
Controlled Study ◽  
Acute Administration ◽  
Open Label ◽  
Glucose Levels ◽  
Adrenal Axis ◽  
Blood Glucose Levels ◽  
Glucagon Like Peptide 1 ◽  
Pituitary Adrenal Axis

AbstractGlucagon-like peptide 1 receptor agonists (GLP-1 RAs) are antidiabetic drugs with effects beyond antihyperglycemic action. The aim of the study was to examine whether a single dose of exenatide could be used as a stimulation test for the pituitary-adrenal axis. We carried out a single-group, open-label pilot clinical trial in an ambulatory setting. Ten healthy volunteers of both sexes with body weight>65 kg and age between 18–50 years were recruited. After fasting for 12 hours the subjects received 10 μg of exenatide solution subcutaneously. Blood samples were taken before the administration of exenatide and up to 150 minutes thereafter. The primary outcome was the maximal level of cortisol after the administration of exenatide. Single administration of exenatide 10 μg resulted in a modest increase in ACTH and cortisol levels, as compared to untreated values, and a decrease in blood glucose levels. Remarkably, a robust suppression of both renin and aldosterone levels occurred. We showed that acute administration of exenatide in a full therapeutic dose modestly stimulates the hypothalamic-pituitary-adrenal axis but inhibits the renin-aldosterone system. Further research is warranted to confirm this finding in the placebo-controlled study.

scholarly journals Update on the Protective Molecular Pathways Improving Pancreatic Beta-Cell Dysfunction

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Alessandra Puddu ◽  
Roberta Sanguineti ◽  
François Mach ◽  
Franco Dallegri ◽  
Giorgio Luciano Viviani ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Dysfunction ◽  
Molecular Pathways ◽  
Cell Dysfunction

The primary function of pancreatic beta-cells is to produce and release insulin in response to increment in extracellular glucose concentrations, thus maintaining glucose homeostasis. Deficient beta-cell function can have profound metabolic consequences, leading to the development of hyperglycemia and, ultimately, diabetes mellitus. Therefore, strategies targeting the maintenance of the normal function and protecting pancreatic beta-cells from injury or death might be crucial in the treatment of diabetes. This narrative review will update evidence from the recently identified molecular regulators preserving beta-cell mass and function recovery in order to suggest potential therapeutic targets against diabetes. This review will also highlight the relevance for novel molecular pathways potentially improving beta-cell dysfunction.

scholarly journals Iron overload is related to elevated blood glucose levels in obese children and aggravates high glucose-induced endothelial cell dysfunction in vitro

2020 ◽  
Vol 8 (1) ◽  
pp. e001426
Author(s):  
Wei Wu ◽  
Jinna Yuan ◽  
Yu Shen ◽  
Yunxian Yu ◽  
Xuefeng Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Iron Overload ◽  
High Glucose ◽  
Metabolic Disorders ◽  
Control Group ◽  
Endothelial Cell Dysfunction ◽  
Obese Children ◽  
Glucose Levels ◽  
Cell Dysfunction ◽  
Blood Glucose Levels

IntroductionThis study was performed to investigate the role of iron overload in the early stage of hyperglycemia-induced vascular functional impairment.Research design and methodsA total of 196 obese children were enrolled, and data regarding ferritin levels, blood glucose levels, intima-media thickness of carotid arteries, liver function and fibrosis index, hemoglobin, blood pressure, blood lipids, and inflammation indicators were collected. Ferritin levels were compared with a control group, which consisted of 148 healthy non-obese children who were age-matched and gender-matched. Endothelial cells were cultured in high glucose medium and supplemented with ferric citrate with or without iron remover (deferoxamine), a reducing agent (N-acetyl-cysteine), or a nuclear factor-κB (NF-κB) inhibitor (BAY 11-7082). Apoptosis, oxidative stress, nitric oxide levels, and endothelin content were evaluated. DNA microarray analysis was performed to analyze the expression of genes in the NF-κB signaling pathway.ResultsObese children have significantly higher ferritin levels compared with the control group. Ferritin level was positively correlated with hemoglobin and was related to metabolic disorders, including impaired glucose tolerance, higher blood pressure, dyslipidemia, and impaired hepatic function. Endothelial cells treated with ferric citrate showed a significantly higher rate of apoptosis, higher levels of oxidative stress, and impaired vasomotor function under high glucose conditions. The above effects were rescued by treatment with an iron remover, reducing agent, or NF-κB inhibitor. Further, detection of phosphorylated-p65 distribution in cells confirmed activation of the NF-κB pathway. DNA microarrays and subsequent gene oncology enrichment analyses revealed the main processes activated in cells.ConclusionIncreased ferritin levels are related to impaired glucose tolerance and other metabolic disorders in obese children. At the cellular level, iron overload aggravated the endothelial cell dysfunction caused by high glucose.

scholarly journals Maintaining Blood Glucose Levels in Range (70–150 mg/dL) is Difficult in COVID-19 Compared to Non-COVID-19 ICU Patients—A Retrospective Analysis

2020 ◽  
Vol 9 (11) ◽  
pp. 3635
Author(s):  
Rajat Kapoor ◽  
Lava R. Timsina ◽  
Nupur Gupta ◽  
Harleen Kaur ◽  
Arianna J. Vidger ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Retrospective Analysis ◽  
Insulin Dose ◽  
Glucose Levels ◽  
Cell Dysfunction ◽  
Daily Insulin ◽  
Daily Insulin Dose ◽  
Blood Glucose Levels ◽  
Time In Range ◽  
Insulin Use

Beta cell dysfunction is suggested in patients with COVID-19 infections. Poor glycemic control in ICU is associated with poor patient outcomes. This is a single center, retrospective analysis of 562 patients in an intensive care unit from 1 March to 30 April 2020. We review the time in range (70–150 mg/dL) spent by critically ill COVID-19 patients and non-COVID-19 patients, along with the daily insulin use. Ninety-three in the COVID-19 cohort and 469 in the non-COVID-19 cohort were compared for percentage of blood glucose TIR (70–150 mg/dL) and average daily insulin use. The COVID-19 cohort spent significantly less TIR (70–150 mg/dL) compared to the non-COVID-19 cohort (44.4% vs. 68.5%). Daily average insulin use in the COVID-19 cohort was higher (8.37 units versus 6.17 units). ICU COVID-19 patients spent less time in range (70–150 mg/dL) and required higher daily insulin dose. A higher requirement for ventilator and days on ventilator was associated with a lower TIR. Mortality was lower for COVID-19 patients who achieved a higher TIR.

scholarly journals Effect of Probiotics on the Glucose Levels of Pregnant Women: A Meta-Analysis of Randomized Controlled Trials

Medicina ◽  
2018 ◽  
Vol 54 (5) ◽  
pp. 77 ◽  
Author(s):  
Tzu-Rong Peng ◽  
Ta-Wei Wu ◽  
You-Chen Chao
Keyword(s):  
Blood Glucose ◽  
Randomized Controlled Trials ◽  
Pregnant Women ◽  
Cell Function ◽  
Fasting Blood Glucose ◽  
Controlled Trials ◽  
Model Assessment ◽  
Glucose Levels ◽  
Randomized Controlled ◽  
Blood Glucose Levels

Background: Gestational diabetes mellitus (GDM) is a condition, in which women develop high blood sugar levels during pregnancy without having diabetes. Evidence on the effects of probiotics on the blood glucose levels of women with GDM is inconsistent. Objective: The present study aimed to investigate the effects of probiotics on the blood glucose levels of pregnant women. Methods: Online databases, such as PubMed, Cochrane, and Excerpta Medica Database (EMBASE) were searched for randomized controlled trials (RCTs) published before July 2018. Trials had to meet the inclusion criteria of our study. Methodological quality and risk bias were independently assessed by two reviewers. Data were pooled using a random effects model and were expressed as the mean difference (MD) and 95% confidence interval (CI). Heterogeneity was evaluated and quantified as I2. Results: In total, 12 RCTs were included in this study. Studies have shown that the use of probiotics significantly reduced the fasting blood glucose (FBG) level (MD: −0.10 mmol/L; 95% CI: −0.19, −0.02), insulin concentration (MD: −2.24 μIU/mL; 95% CI: −3.69, −0.79), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score (MD: −0.47; 95% CI: −0.74, −0.21), and Homeostasis model of assessment-estimated β cell function (HOMA-B) score (MD: −20.23; 95% CI: −31.98, −8.49) of pregnant women. In a subgroup analysis, whether the blood glucose-lowering effect of probiotics influenced the diagnosis of pregnant women with GDM was assessed. The results showed that probiotics had significantly reduced the fasting blood glucose (FBG) level (MD: −0.10 mmol/L; 95% CI: −0.17, −0.04) and HOMA-IR score (MD: −0.37; 95% CI: −0.72, −0.02) of pregnant women who were not diagnosed with GDM. Conclusion: Probiotics reduce the blood glucose level of pregnant women, especially without GDM diagnosis. However, further research using RCTs must be conducted to validate the results of the present study.

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