scholarly journals Rice Bran Phenolic Extracts Modulate Insulin Secretion and Gene Expression Associated with β-Cell Function

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1889 ◽  
Author(s):  
Nancy Saji ◽  
Nidhish Francis ◽  
Lachlan J. Schwarz ◽  
Christopher L. Blanchard ◽  
Abishek B. Santhakumar
Keyword(s):  
Insulin Secretion ◽  
Rice Bran ◽  
Cell Function ◽  
Β Cell ◽  
Free Radical Damage ◽  
Glucose Transporter 2 ◽  
Expression Of Genes ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion ◽  
Phenolic Extracts

Oxidative stress is known to modulate insulin secretion and initiate gene alterations resulting in impairment of β-cell function and type 2 diabetes mellitus (T2DM). Rice bran (RB) phenolic extracts contain bioactive properties that may target metabolic pathways associated with the pathogenesis of T2DM. This study aimed to examine the effect of stabilized RB phenolic extracts on the expression of genes associated with β-cell function such as glucose transporter 2 (Glut2), pancreatic and duodenal homeobox 1 (Pdx1), sirtuin 1 (Sirt1), mitochondrial transcription factor A (Tfam), and insulin 1 (Ins1) in addition to evaluating its impact on glucose-stimulated insulin secretion. It was observed that treatment with different concentrations of RB phenolic extracts (25-250 µg/mL) significantly increased the expression of Glut2, Pdx1, Sirt1, Tfam, and Ins1 genes and glucose-stimulated insulin secretion under both normal and high glucose conditions. RB phenolic extracts favourably modulated the expression of genes involved in β-cell dysfunction and insulin secretion via several mechanisms such as synergistic action of polyphenols targeting signalling molecules, decreasing free radical damage by its antioxidant activity, and stimulation of effectors or survival factors of insulin secretion.

scholarly journals Coloured Rice Phenolic Extracts Increase Expression of Genes Associated with Insulin Secretion in Rat Pancreatic Insulinoma β-cells

2020 ◽  
Vol 21 (9) ◽  
pp. 3314
Author(s):  
Gideon Gatluak Kang ◽  
Nidhish Francis ◽  
Rodney Hill ◽  
Daniel LE Waters ◽  
Christopher L. Blanchard ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Glucose Transporter 2 ◽  
Expression Of Genes ◽  
Β Cell Function ◽  
The Impact ◽  
Phenolic Extracts

Glucose-induced oxidative stress is associated with the overproduction of reactive oxygen species (ROS), which may dysregulate the expression of genes controlling insulin secretion leading to β-cell dysfunction, a hallmark of type 2 diabetes mellitus (T2DM). This study investigated the impact of coloured rice phenolic extracts (CRPEs) on the expression of key genes associated with β-cell function in pancreatic β-cells (INS-1E). These genes included glucose transporter 2 (Glut2), silent mating type information regulation 2 homolog 1 (Sirt1), mitochondrial transcription factor A (Tfam), pancreatic/duodenal homeobox protein 1 (Pdx-1) and insulin 1 (Ins1). INS-1E cells were cultured in high glucose (25 mM) to induce glucotoxic stress conditions (HGSC) and in normal glucose conditions (NGC-11.1 mM) to represent normal β-cell function. Cells were treated with CRPEs derived from two coloured rice cultivars, Purple and Yunlu29-red varieties at concentrations ranged from 50 to 250 µg/mL. CRPEs upregulated the expression of Glut2, Sirt1 and Pdx-1 significantly at 250 µg/mL under HGSC. CRPEs from both cultivars also upregulated Glut2, Sirt1, Tfam, Pdx-1 and Ins1 markedly at 250 µg/mL under NGC with Yunlu29 having the greatest effect. These data suggest that CRPEs may reduce β-cell dysfunction in T2DM by upregulating the expression of genes involved in insulin secretion pathways.

scholarly journals Bioactive Phytochemicals Isolated from Akebia quinata Enhances Glucose-Stimulated Insulin Secretion by Inducing PDX-1

Plants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1087
Author(s):  
Dahae Lee ◽  
Jin Su Lee ◽  
Jurdas Sezirahiga ◽  
Hak Cheol Kwon ◽  
Dae Sik Jang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Experimental Studies ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Etoh Extract ◽  
Chemical Structures ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion ◽  
Phosphoinositide 3 Kinase

Chocolate vine (Akebia quinata) is consumed as a fruit and is also used in traditional medicine. In order to identify the bioactive components of A. quinata, a phytosterol glucoside stigmasterol-3-O-β-d-glucoside (1), three triterpenoids maslinic acid (2), scutellaric acid (3), and hederagenin (4), and three triterpenoidal saponins akebia saponin PA (5), hederacoside C (6), and hederacolchiside F (7) were isolated from a 70% EtOH extract of the fruits of A. quinata (AKQU). The chemical structures of isolates 1–7 were determined by analyzing the 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data. Here, we evaluated the effects of AKQU and compounds 1–7 on insulin secretion using the INS-1 rat pancreatic β-cell line. Glucose-stimulated insulin secretion (GSIS) was evaluated in INS-1 cells using the GSIS assay. The expression levels of the proteins related to pancreatic β-cell function were detected by Western blotting. Among the isolates, stigmasterol-3-O-β-d-glucoside (1) exhibited strong GSIS activity and triggered the overexpression of pancreas/duodenum homeobox protein-1 (PDX-1), which is implicated in the regulation of pancreatic β-cell survival and function. Moreover, isolate 1 markedly induced the expression of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), insulin receptor substrate-2 (IRS-2), phosphoinositide 3-kinase (PI3K), and Akt, which regulate the transcription of PDX-1. The results of our experimental studies indicated that stigmasterol-3-O-β-d-glucoside (1) isolated from the fruits of A. quinata can potentially enhance insulin secretion, and might alleviate the reduction in GSIS during the development of T2DM.

scholarly journals Protein restriction in early life is associated with changes in insulin sensitivity and pancreatic β-cell function during pregnancy

2012 ◽  
Vol 109 (2) ◽  
pp. 236-247 ◽  
Author(s):  
Letícia Martins Ignácio-Souza ◽  
Sílvia Regina Reis ◽  
Vanessa Cristina Arantes ◽  
Bárbara Laet Botosso ◽  
Roberto Vilela Veloso ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Early Life ◽  
Cell Function ◽  
Secretory Process ◽  
Insulin Biosynthesis ◽  
Β Cell ◽  
Pregnant Rats ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion

Malnutrition in early life impairs glucose-stimulated insulin secretion in adulthood. Conversely, pregnancy is associated with a significant increase in glucose-stimulated insulin secretion under conditions of normoglycaemia. A failure in β-cell adaptive changes may contribute to the onset of diabetes. Thus, glucose homeostasis and β-cell function were evaluated in control-fed pregnant (CP) and non-pregnant (CNP) or protein-restricted pregnant (LPP) and non-pregnant (LPNP) rats, from fetal to adult life, and in protein-restricted rats that were recovered after weaning (RP and RNP). The typical insulin resistance of pregnancy was not observed in the RP rats, nor did pregnancy increase the insulin content/islet in the LPP group. The glucose dose–response curves from pregnant rats were shifted to the left in relation to the non-pregnant rats, except in the recovered group. Glucose utilisation but not oxidation in islets from the RP and LPP groups was reduced at a concentration of 8·3 mm-glucose compared with islets from the CP group. Cyclic AMP content and the potentiation of glucose-stimulated insulin secretion by isobutylmethylxanthine at a concentration of 2·8 mm-glucose indicated increased adenylyl cyclase 3 activity but reduced protein kinase A-α activity in islets from the RP and LPP rats. Protein kinase C (PKC)-α but not phospholipase C (PLC)-β1 expression was reduced in islets from the RP group. Phorbol-12-myristate 13-acetate produced a less potent stimulation of glucose-stimulated insulin secretion in the RP group. Thus, the alterations exhibited by islets from the LPP group appeared to be due to reduced islet mass and/or insulin biosynthesis. In the RP group the loss of the adaptive capacity apparently resulted from uncoupling between glucose metabolism and the amplifying signals of the secretory process, as well as a severe attenuation of the PLC/PKC pathway.

scholarly journals Spontaneous restoration of functional β-cell mass in obese SM/J mice

2020 ◽  
Author(s):  
Mario A Miranda ◽  
Caryn Carson ◽  
Celine L St Pierre ◽  
Juan F Macias-Velasco ◽  
Jing W Hughes ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Mitotic Index ◽  
Cell Function ◽  
Cell Mass ◽  
Β Cell ◽  
Physiological Mechanisms ◽  
Β Cell Function ◽  
Basal Insulin Secretion ◽  
Glucose Stimulated Insulin Secretion ◽  
Mass Expansion

AbstractMaintenance of functional β-cell mass is critical to preventing diabetes, but the physiological mechanisms that cause β-cell populations to thrive or fail in the context of obesity are unknown. High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we characterize insulin homeostasis, islet morphology, and β-cell function during SM/J’s diabetic remission. As they resolve hyperglycemia, obese SM/J mice dramatically increase circulating and pancreatic insulin levels while improving insulin sensitivity. Immunostaining of pancreatic sections reveals that obese SM/J mice selectively increase β-cell mass but not α-cell mass. Obese SM/J mice do not show elevated β-cell mitotic index, but rather elevated α-cell mitotic index. Functional assessment of isolated islets reveals that obese SM/J mice increase glucose stimulated insulin secretion, decrease basal insulin secretion, and increase islet insulin content. These results establish that β-cell mass expansion and improved β-cell function underlie the resolution of hyperglycemia, indicating that obese SM/J mice are a valuable tool for exploring how functional β-cell mass can be recovered in the context of obesity.

scholarly journals Emerging role of testosterone in pancreatic β cell function and insulin secretion

2019 ◽  
Vol 240 (3) ◽  
pp. R97-R105 ◽  
Author(s):  
Weiwei Xu ◽  
Jamie Morford ◽  
Franck Mauvais-Jarvis
Keyword(s):  
Insulin Secretion ◽  
Metabolic Regulation ◽  
Cell Function ◽  
Visceral Obesity ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion

One of the most sexually dimorphic aspects of metabolic regulation is the bidirectional modulation of glucose homeostasis by testosterone in male and females. Severe testosterone deficiency predisposes men to type 2 diabetes (T2D), while in contrast, androgen excess predisposes women to hyperglycemia. The role of androgen deficiency and excess in promoting visceral obesity and insulin resistance in men and women respectively is well established. However, although it is established that hyperglycemia requires β cell dysfunction to develop, the role of testosterone in β cell function is less understood. This review discusses recent evidence that the androgen receptor (AR) is present in male and female β cells. In males, testosterone action on AR in β cells enhances glucose-stimulated insulin secretion by potentiating the insulinotropic action of glucagon-like peptide-1. In females, excess testosterone action via AR in β cells promotes insulin hypersecretion leading to oxidative injury, which in turn predisposes to T2D.

scholarly journals Role of the Rho-ROCK (Rho-Associated Kinase) Signaling Pathway in the Regulation of Pancreatic β-Cell Function

Endocrinology ◽  
2008 ◽  
Vol 150 (5) ◽  
pp. 2072-2079 ◽  
Author(s):  
Eva Hammar ◽  
Alejandra Tomas ◽  
Domenico Bosco ◽  
Philippe A. Halban
Keyword(s):  
Extracellular Matrix ◽  
Insulin Secretion ◽  
Actin Cytoskeleton ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion ◽  
And Function

Extracellular matrix has a beneficial impact on β-cell spreading and function, but the underlying signaling pathways have yet to be fully elucidated. In other cell types, Rho, a well-characterized member of the family of Rho GTPases, and its effector Rho-associated kinase (ROCK), play an important role as downstream mediators of outside in signaling from extracellular matrix. Therefore, a possible role of the Rho-ROCK pathway in β-cell spreading, actin cytoskeleton dynamics, and function was investigated. Rho was inhibited using a new cell-permeable version of C3 transferase, whereas the activity of ROCK was repressed using the specific ROCK inhibitors H-1152 and Y-27632. Inhibition of Rho and of ROCK increased spreading and improved both short-term and prolonged glucose-stimulated insulin secretion but had no impact on basal secretion. Inhibition of this pathway led to a depolymerization of the actin cytoskeleton. Furthermore, the impact of the inhibition of ROCK on stimulated insulin secretion was acute and reversible, suggesting that rapid signaling such as phosphorylation is involved. Finally, quantification of the activity of RhoA indicated that the extracellular matrix represses RhoA activity. Overall these results show for the first time that the Rho-ROCK signaling pathway contributes to the stabilization of the actin cytoskeleton and inhibits glucose-stimulated insulin secretion in primary pancreatic β-cells. Furthermore, they indicate that inhibition of this pathway might be one of the mechanisms by which the extracellular matrix exerts its beneficial effects on pancreatic β-cell function.

scholarly journals Mitochondrial Efflux of Citrate and Isocitrate is Fully Dispensable for Glucose-Stimulated Insulin Secretion and Pancreatic Islet β-Cell Function

2021 ◽  
Author(s):  
Casey J. Bauchle ◽  
Kristen E. Rohli ◽  
Cierra K. Boyer ◽  
Vidhant Pal ◽  
Jonathan V. Rocheleau ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Glucose Homeostasis ◽  
Cell Function ◽  
Normal Glucose Tolerance ◽  
Coupling Factor ◽  
Β Cell ◽  
Metabolic Coupling ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion

The defining feature of pancreatic islet β-cell function is the precise coordination of changes in blood glucose levels with insulin secretion to regulate systemic glucose homeostasis. While ATP has long been heralded as a critical metabolic coupling factor to trigger insulin release, glucose-derived metabolites have been suggested to further amplify fuel-stimulated insulin secretion. The mitochondrial export of citrate and isocitrate through the citrate-isocitrate carrier (CIC) has been suggested to initiate a key pathway that amplifies glucose-stimulated insulin secretion, though the physiological significance of β-cell CIC to glucose homeostasis has not been established. Here, we generated constitutive and adult CIC β-cell knockout mice and demonstrate these animals have normal glucose tolerance, similar responses to diet-induced obesity, and identical insulin secretion responses to various fuel secretagogues. Glucose-stimulated NADPH production was impaired in β-cell CIC KO islets, whereas glutathione reduction was retained. Furthermore, suppression of the downstream enzyme, cytosolic isocitrate dehydrogenase, Idh1, inhibited insulin secretion in wild type islets, but failed to impact β-cell function in β-cell CIC KO islets.<b> </b>Our data demonstrate that the mitochondrial citrate-isocitrate carrier is not required for glucose-stimulated insulin secretion, and that additional complexities exist for the role of Idh1 and NADPH in the regulation of β-cell function.

Mitochondrial efflux of citrate and isocitrate is fully dispensable for glucose-stimulated insulin secretion and pancreatic islet β-cell function

Diabetes ◽  
2021 ◽  
pp. db210037
Author(s):  
Casey J. Bauchle ◽  
Kristen E. Rohli ◽  
Cierra K. Boyer ◽  
Vidhant Pal ◽  
Jonathan V. Rocheleau ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Cell Function ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion

scholarly journals Markers of Islet Endothelial Dysfunction Occur in Male B6.BKS(D)-Leprdb/J Mice and May Contribute to Reduced Insulin Release

Endocrinology ◽  
2016 ◽  
Vol 158 (2) ◽  
pp. 293-303 ◽  
Author(s):  
Meghan F. Hogan ◽  
Amy W. Liu ◽  
Michael J. Peters ◽  
Joshua R. Willard ◽  
Zaheen Rabbani ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Insulin Secretion ◽  
Endothelial Dysfunction ◽  
Cell Function ◽  
High Fat ◽  
Advanced Glycation ◽  
Β Cell ◽  
Protein Levels ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion

Abstract Islet endothelial cells produce paracrine factors that support β-cell function and growth. Endothelial dysfunction underlies diabetic microvascular complications; thus, we hypothesized that in diabetes, islet endothelial cells become dysfunctional, which may contribute to β-cell secretory dysfunction. Islets/islet endothelial cells were isolated from diabetic B6.BKS(D)-Leprdb/J male (db/db) mice, treated with or without the glucose-lowering agent phlorizin, or from C57BL/6J mice fed a high-fat diet for 18 weeks and appropriate controls. Messenger RNA (mRNA) and/or the protein levels of the cell adhesion molecule E-selectin (Sele), proinflammatory cytokine interleukin-6 (Il6), vasoconstrictor endothelin-1 (Edn1), and endothelial nitric oxide synthase (Nos3; Nos3) were evaluated, along with advanced glycation end product immunoreactivity. Furthermore, an islet endothelial cell line (MS-1) was exposed to diabetic factors (glucose, palmitate, insulin, and tumor necrosis factor-α) for six days. Conditioned media were collected from these cells, incubated with isolated islets, and glucose-stimulated insulin secretion and insulin content were assessed. Islet endothelial cells from db/db mice exhibited increased Sele, Il6, and Edn1 mRNA levels, decreased Nos3 protein, and accumulation of advanced glycation end products. Phlorizin treatment significantly increased Nos3 protein levels but did not alter expression of the other markers. High-fat feeding in C57BL/6J mice resulted in increased islet Sele, Il6, and Edn1 but no change in Nos3. Exposure of islets to conditioned media from MS-1 cells cultured in diabetic conditions resulted in a 50% decrease in glucose-stimulated insulin secretion and 30% decrease in insulin content. These findings demonstrate that, in diabetes, islet endothelial cells show evidence of a dysfunctional phenotype, which may contribute to loss of β-cell function.

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