Ameliorating activity of polyphenolic-rich extracts of Basella rubra L. leaves on pancreatic β-cell dysfunction in streptozotocin-induced diabetic rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Basiru Olaitan Ajiboye ◽  
Amaka Diayi ◽  
Shedrach Oludare Agunbiade ◽  
Ayodele Jacob Akinyemi ◽  
Olusola Bolaji Adewale ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Serum Lipid ◽  
Serum Insulin ◽  
Pancreatic Beta Cell ◽  
Total Phenolic ◽  
Gamma Glutamyl Transferase ◽  
Dependent Manner ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Glutamyl Transferase

Abstract Objectives To assess the ameliorative activity of polyphenolic-rich extracts of Basella rubra leaves on β-cell dysfunction in type-II diabetes (T2DM). Methods Total phenolic and flavonoid contents; α-amylase and α-glucosidase inhibitory actions and qualitative analysis of the bioactive compounds of the polyphenolic-rich extract of B. rubra leaves were investigated using gas chromatography-mass spectroscopy (GC-MS). Diabetes mellitus (DM) was induced by single intraperitoneal injection of streptozotocin (60 mg/kg body weight) and the rats were orally given bound phenolic (BPE) and free phenolic extracts (FPE) of B. rubra (B.R) leaves at 200 and 400 mg/kg b.w once daily for 14 days. Biochemical analyses were executed for evaluation of serum insulin, serum lipid profile concentrations, liver enzymes activities. Results The extracts demonstrated antioxidant potentials and enzymes inhibitory activities in dose dependent manner; and several bioactive compounds as revealed by GC-MS. BPE and FPE considerably (p<0.05) reduced hyperglycemia, improved serum insulin levels, ameliorated the concentration of serum lipid profiles and improved liver antioxidant activities. Additionally, BPE and FPE expressively decreased alanine aminotransferases (ALT), aspartate aminotransferases (AST), gamma-glutamyl transferase (GGT) activities along with levels of bilirubin and urea when compare to diabetic control rats. Conclusions Data acquired exhibited the ability of BPE and FPE to improve pancreatic beta-cell in streptozotocin-induced rats.

scholarly journals Inhibition of inositol-requiring enzyme 1α RNase activity protects pancreatic beta cell and improves diabetic condition in insulin mutation-induced diabetes

2020 ◽  
Author(s):  
Oana Herlea-Pana ◽  
Venkateswararao Eeda ◽  
Ram Babu Undi ◽  
Iulia Rus ◽  
Hui-Ying Lim ◽  
...  
Keyword(s):  
Er Stress ◽  
Serum Insulin ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Expression Of Genes ◽  
And Function ◽  
Akita Mice

ABSTRACTProinsulin misfolding in the endoplasmic reticulum (ER) plays an important role in β-cell dysfunction and death and the pathogenesis of mutant INS-gene-induced diabetes of youth (MIDY). There is no effective treatment for MIDY except the insulin administration. Here, we found that the ER stress sensor inositol-requiring enzyme 1α (IRE1α) was activated in the Akita mice, a mouse model of MIDY. Normalization of IRE1α RNase hyperactivity by pharmacological inhibitors significantly ameliorated the hyperglycemic conditions and increased serum insulin levels in Akita mice. These benefits were accompanied by a concomitant protection of functional β-cell mass, as shown by the suppression of β-cell apoptosis, increase in mature insulin production and reduction of proinsulin level. At the molecular level, we observed that the expression of genes associated with β-cell identity and function was significantly up-regulated and ER stress and its associated inflammation and oxidative stress were suppressed in islets from Akita mice treated with IRE1α RNase inhibitors. This study provides the first evidence of the in vivo efficacy of IRE1α RNase inhibition in Akita mice, pointing to the possibility of targeting IRE1α RNase as a therapeutic direction for the treatment of MIDY diabetes.

scholarly journals Ameliorative Activity of Ethanol Extract of Artocarpus heterophyllus Stem Bark on Pancreatic β-Cell Dysfunction in Alloxan-Induced Diabetic Rats

2016 ◽  
Vol 22 (4) ◽  
pp. 538-543 ◽  
Author(s):  
Basiru O. Ajiboye ◽  
Oluwafemi A. Ojo ◽  
Oluwatosin Adeyonu ◽  
Oluwatosin D. Imiere ◽  
Adewale O. Fadaka ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Serum Insulin ◽  
Ethanol Extract ◽  
Stem Bark ◽  
Diabetic Rats ◽  
Antioxidant Enzyme Activities ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Artocarpus Heterophyllus ◽  
Cell Dysfunction

This study sought to investigate the ameliorative effects of ethanol extract Artocarpus heterophyllus (EAH) in alloxan-induced diabetic rats. The rats were divided into 6 groups, with groups 1 and 2 serving as nondiabetic and diabetic control, respectively; group 3 serving as diabetic rats treated with 5 mg/kg glibenclamide; and groups 4 to 6 were diabetic rats treated with 50, 100, and 150 mg/kg of EAH, respectively. Assays determined were serum insulin, lipid peroxidation, and antioxidant enzyme activities. EAH stem bark reduced fasting blood glucose and lipid peroxidation levels and increased serum insulin levels and activities of antioxidant enzymes. Data obtained demonstrated the ability of EAH stem bark to ameliorate pancreatic β-cell dysfunction in alloxan-induced diabetic rats.

scholarly journals Sex-biased islet β cell dysfunction is caused by the MODY MAFA S64F variant by inducing premature aging and senescence in males

2020 ◽  
Author(s):  
Emily M. Walker ◽  
Jeeyeon Cha ◽  
Xin Tong ◽  
Min Guo ◽  
Jin-Hua Liu ◽  
...  
Keyword(s):  
Cell Function ◽  
Premature Aging ◽  
Calcium Handling ◽  
Secretory Proteins ◽  
Dependent Manner ◽  
Β Cell ◽  
Functional Changes ◽  
Protein Levels ◽  
Cell Dysfunction ◽  
Β Cell Function

AbstractA heterozygous missense mutation producing a variant of the islet β-cell-enriched MAFA transcription factor (Ser(S)64Phe(F) MAFA) was identified in humans who developed adult-onset, β-cell dysfunction (diabetes or insulinomatosis), with men more prone to diabetes. This mutation engenders increased stability to the normally unstable MAFA protein. To obtain insight into how this variant impacts β cell function, we developed a mouse model expressing S64F MafA and found sex-dependent phenotypes, with heterozygous mutant males displaying impaired glucose tolerance while females were slightly hypoglycemic with improved blood glucose clearance. Only heterozygous males showed transiently higher MafA protein levels preceding the onset of glucose intolerance and sex-dependent, differential expression of genes involved in calcium signaling, DNA damage, aging, and senescence. Functional changes in islet calcium handling and signs of islet aging and senescence processes were uniquely observed in male animals. In addition, S64F MAFA expression in human, male EndoC-βH2 β cells accelerated cellular senescence and increased production of senescence-associated secretory proteins compared to cells expressing wild-type MAFA. Together, these results implicate a conserved mechanism of accelerated islet aging and senescence in promoting diabetes in S64F MAFA carriers in a sex-dependent manner.

scholarly journals Induction of core circadian clock transcription factor Bmal1 enhances β cell function and protects against obesity-induced glucose intolerance

2020 ◽  
Author(s):  
Ada Admin ◽  
Kuntol Rakshit ◽  
Aleksey V. Matveyenko
Keyword(s):  
Transcription Factor ◽  
Insulin Secretion ◽  
Circadian Clock ◽  
Glucose Intolerance ◽  
Target Genes ◽  
Cell Function ◽  
Dependent Manner ◽  
Β Cell ◽  
Cell Dysfunction

Type 2 diabetes mellitus (T2DM) is characterized by β cell dysfunction due to impaired glucose-stimulated insulin secretion (GSIS). Studies show that β cell circadian clocks are important regulators of GSIS and glucose homeostasis. These observations raise the question whether enhancement of the circadian clock in β cells will confer protection against β cell dysfunction under diabetogenic conditions. To test this we employed an approach by first generating mice with β cell-specific inducible overexpression of <i>Bmal1</i> (core circadian transcription factor; <i>β-Bmal1<sup>OV</sup></i>). We subsequently examined the effects of <i>β-Bmal1<sup>OV</sup> </i>on the circadian clock, GSIS, islet transcriptome, and glucose metabolism in context of diet-induced obesity. We additionally tested the effects of circadian clock-enhancing small molecule Nobiletin on GSIS in mouse and human control and T2DM islets. We report that <i>β-Bmal1<sup>OV</sup> </i>mice display<i> </i>enhanced islet circadian clock amplitude, augmented <i>in vivo</i> and <i>in vitro</i> GSIS and are protected against obesity-induced glucose intolerance. These effects were associated with increased expression of purported BMAL1-target genes mediating insulin secretion, processing, and lipid metabolism. Furthermore, exposure of isolated islets to Nobiletin enhanced β cell secretory function in <i>Bmal1</i>-dependent manner. This work suggests therapeutic targeting of the circadian system as a potential strategy to counteract β cell failure under diabetogenic conditions.

scholarly journals The Investigation of Antidiabetic Effects of Leontice leontopetalum Extract on Human Pancreatic β Cell Lines (1.1B4) Treated with Streptozotocin

2018 ◽  
Vol 6 (6) ◽  
pp. 792
Author(s):  
Celal Güven ◽  
Eylem Taşkın ◽  
Önder Yumrutaş ◽  
Leyla Türker Şener ◽  
Fulya Dal ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Survival ◽  
Pancreatic Beta Cell ◽  
Insulin Content ◽  
Dependent Manner ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Glucose Levels ◽  
Dose Dependent ◽  
Antidiabetic Effects

One of the alternative therapeutic methods is herbal medicine. Leontice leontopetalum belongs to Berberidaceae family. The aim of study was investigated the extract of LL on human pancreatic beta cell-treated with STZ. Materials and methods: The human pancreatic beta cell (1.1B4) line was used the current study. LL’s extracts (1, 10, 100, and 1000 ug/ml) were supplemented in media for twenty-four hours and/or after STZ treatment (10 and 20 mM). Cells survivals (MTT), cells proliferation were shown by using xCelligence. Insulin content and releasing were measured at 1.1, 8.4 and 16.7 mM glucose concentrations. Results: The result of MTT was shown that cell survival was decreased, based on dose-dependent. When looked at xCelligence results, cell proliferation in STZ groups and the lowest and highest concentrations of LL were attenuated in a dose-dependent manner. Also, cotreatments of LL and STZ were decreased as well. The result of insulin-releasing on glucose induction was shown that STZ concentration gave rise to reduce insulin content at low and high glucose levels. Also, co-treatment of LL and STZ attenuated insulin content based on dose. Conclusion: It was considered that LL treatment led to increased insulin realizing, resulting from decreasing insulin content in diabetic beta cells, but decrease cell survival.

PRMT1 promotes glucose toxicity-induced β cell dysfunction by regulating the nucleo-cytoplasmic trafficking of PDX-1 in a FOXO1-dependent manner in INS-1 cells

Endocrine ◽  
2015 ◽  
Vol 49 (3) ◽  
pp. 669-682 ◽  
Author(s):  
Lixia Lv ◽  
Hewen Chen ◽  
Jiaying Sun ◽  
Di Lu ◽  
Chen Chen ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Β Cell ◽  
Glucose Toxicity ◽  
Cell Dysfunction

scholarly journals Induction of core circadian clock transcription factor Bmal1 enhances β cell function and protects against obesity-induced glucose intolerance

2020 ◽  
Author(s):  
Ada Admin ◽  
Kuntol Rakshit ◽  
Aleksey V. Matveyenko
Keyword(s):  
Transcription Factor ◽  
Insulin Secretion ◽  
Circadian Clock ◽  
Glucose Intolerance ◽  
Target Genes ◽  
Cell Function ◽  
Dependent Manner ◽  
Β Cell ◽  
Cell Dysfunction

Type 2 diabetes mellitus (T2DM) is characterized by β cell dysfunction due to impaired glucose-stimulated insulin secretion (GSIS). Studies show that β cell circadian clocks are important regulators of GSIS and glucose homeostasis. These observations raise the question whether enhancement of the circadian clock in β cells will confer protection against β cell dysfunction under diabetogenic conditions. To test this we employed an approach by first generating mice with β cell-specific inducible overexpression of <i>Bmal1</i> (core circadian transcription factor; <i>β-Bmal1<sup>OV</sup></i>). We subsequently examined the effects of <i>β-Bmal1<sup>OV</sup> </i>on the circadian clock, GSIS, islet transcriptome, and glucose metabolism in context of diet-induced obesity. We additionally tested the effects of circadian clock-enhancing small molecule Nobiletin on GSIS in mouse and human control and T2DM islets. We report that <i>β-Bmal1<sup>OV</sup> </i>mice display<i> </i>enhanced islet circadian clock amplitude, augmented <i>in vivo</i> and <i>in vitro</i> GSIS and are protected against obesity-induced glucose intolerance. These effects were associated with increased expression of purported BMAL1-target genes mediating insulin secretion, processing, and lipid metabolism. Furthermore, exposure of isolated islets to Nobiletin enhanced β cell secretory function in <i>Bmal1</i>-dependent manner. This work suggests therapeutic targeting of the circadian system as a potential strategy to counteract β cell failure under diabetogenic conditions.

scholarly journals RIPK3-mediated inflammation is a conserved β cell response to ER stress

2020 ◽  
Vol 6 (51) ◽  
pp. eabd7272
Author(s):  
Bingyuan Yang ◽  
Lisette A. Maddison ◽  
Karolina E. Zaborska ◽  
Chunhua Dai ◽  
Linlin Yin ◽  
...  
Keyword(s):  
Er Stress ◽  
Cell Response ◽  
Dependent Manner ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Proinflammatory Mediators ◽  
Islet Inflammation

Islet inflammation is an important etiopathology of type 2 diabetes; however, the underlying mechanisms are not well defined. Using complementary experimental models, we discovered RIPK3-dependent IL1B induction in β cells as an instigator of islet inflammation. In cultured β cells, ER stress activated RIPK3, leading to NF-kB–mediated proinflammatory gene expression. In a zebrafish muscle insulin resistance model, overnutrition caused islet inflammation, β cell dysfunction, and loss in an ER stress–, ripk3-, and il1b-dependent manner. In mouse islets, high-fat diet triggered the IL1B expression in β cells before macrophage recruitment in vivo, and RIPK3 inhibition suppressed palmitate-induced β cell dysfunction and Il1b expression in vitro. Furthermore, in human islets grafted in hyperglycemic mice, a marked increase in ER stress, RIPK3, and NF-kB activation in β cells were accompanied with murine macrophage infiltration. Thus, RIPK3-mediated induction of proinflammatory mediators is a conserved, previously unrecognized β cell response to metabolic stress and a mediator of the ensuing islet inflammation.

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