scholarly journals Development and Characteristics of Pancreatic Epsilon Cells

2019 ◽  
Vol 20 (8) ◽  
pp. 1867 ◽  
Author(s):  
Naoaki Sakata ◽  
Gumpei Yoshimatsu ◽  
Shohta Kodama
Keyword(s):  
Transcription Factors ◽  
Blood Glucose ◽  
Endocrine Cells ◽  
Current Evidence ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Ghrelin Gene ◽  
Pancreatic Endocrine Cells

Pancreatic endocrine cells expressing the ghrelin gene and producing the ghrelin hormone were first identified in 2002. These cells, named ε cells, were recognized as the fifth type of endocrine cells. Differentiation of ε cells is induced by various transcription factors, including Nk2 homeobox 2, paired box proteins Pax-4 and Pax6, and the aristaless-related homeobox. Ghrelin is generally considered to be a “hunger hormone” that stimulates the appetite and is produced mainly by the stomach. Although the population of ε cells is small in adults, they play important roles in regulating other endocrine cells, especially β cells, by releasing ghrelin. However, the roles of ghrelin in β cells are complex. Ghrelin contributes to increased blood glucose levels by suppressing insulin release from β cells and is also involved in the growth and proliferation of β cells and the prevention of β cell apoptosis. Despite increasing evidence and clarification of the mechanisms of ε cells over the last 20 years, many questions remain to be answered. In this review, we present the current evidence for the participation of ε cells in differentiation and clarify their characteristics by focusing on the roles of ghrelin.

Glucose regulation of insulin gene expression in pancreatic β-cells

2008 ◽  
Vol 415 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Sreenath S. Andrali ◽  
Megan L. Sampley ◽  
Nathan L. Vanderford ◽  
Sabire Özcan
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Blood Glucose ◽  
Insulin Gene ◽  
Β Cells ◽  
Β Cell ◽  
Insulin Synthesis ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Insulin Gene Expression

Production and secretion of insulin from the β-cells of the pancreas is very crucial in maintaining normoglycaemia. This is achieved by tight regulation of insulin synthesis and exocytosis from the β-cells in response to changes in blood glucose levels. The synthesis of insulin is regulated by blood glucose levels at the transcriptional and post-transcriptional levels. Although many transcription factors have been implicated in the regulation of insulin gene transcription, three β-cell-specific transcriptional regulators, Pdx-1 (pancreatic and duodenal homeobox-1), NeuroD1 (neurogenic differentiation 1) and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A), have been demonstrated to play a crucial role in glucose induction of insulin gene transcription and pancreatic β-cell function. These three transcription factors activate insulin gene expression in a co-ordinated and synergistic manner in response to increasing glucose levels. It has been shown that changes in glucose concentrations modulate the function of these β-cell transcription factors at multiple levels. These include changes in expression levels, subcellular localization, DNA-binding activity, transactivation capability and interaction with other proteins. Furthermore, all three transcription factors are able to induce insulin gene expression when expressed in non-β-cells, including liver and intestinal cells. The present review summarizes the recent findings on how glucose modulates the function of the β-cell transcription factors Pdx-1, NeuroD1 and MafA, and thereby tightly regulates insulin synthesis in accordance with blood glucose levels.

scholarly journals β-Cell Induction In Vivo in Severely Diabetic Male Mice by Changing the Circulating Levels and Pattern of the Ratios of Estradiol to Androgens

Endocrinology ◽  
2014 ◽  
Vol 155 (10) ◽  
pp. 3829-3842 ◽  
Author(s):  
Akari Inada ◽  
Oogi Inada ◽  
Nobuharu L. Fujii ◽  
Kei Fujishima ◽  
Tetsuichiro Inai ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Male Mice ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Severe Diabetes ◽  
Cell Induction ◽  
Circulating Levels

Abstract Previously we have generated transgenic (Tg) mice developing severe diabetes early in life with a profound depletion of β-cells with β-cell-directed expression of inducible cAMP early repressor-Iγ. Only male mice continue to demonstrate hyperglycemia throughout life. To investigate this sexual dimorphism, we treated severely diabetic male Tg mice with orchiectomy (ORX) or 17β-estradiol (E2) pellet implantation alone or in combination with ORX and E2-implantation to change the circulating levels and patterns of the ratio of estradiol to androgens. In the Tg-ORX group, the blood-glucose levels decreased to a certain level within several weeks but never reached the female Tg-control level. In contrast, the Tg-ORX+E2 or Tg-E2 group showed a more rapid drop in blood glucose to the basal level with a substantial increase in β-cells, thus preventing the occurrence of severe diabetes in the male mice. The β-cells, not only within islet but also in and adjacent to ducts and scattered β-cell clusters, were strongly induced by 1 week after treatment, and the islet morphology dramatically changed. Enhanced β-cell induction in the ducts occurred concomitantly with markedly increased levels of pancreatic duodenal homeobox-1 and related transcription factors. The glucose-lowering and β-cell-increasing effects were independent of the age at which the treatment is started. These data provide evidence that the circulating level of E2 and the ratio of E2 to T greatly affect the blood glucose levels, the β-cell induction, and the islet morphology in diabetic male Tg mice. This novel mechanism offers great potential for developing strategies to increase the number of β-cells in vivo.

scholarly journals Antidiabetes of Combination of Fractionated-extracts of Andrographispaniculata and Centellaasiatica in Neonatal Streptozotocin-induced Diabetic Rats

2020 ◽  
pp. 312-322
Author(s):  
Reni Ariesta ◽  
La Ode Muhammad Fitrawan ◽  
Agung Endro Nugroho ◽  
Suwidjiyo Pramono
Keyword(s):  
Blood Glucose ◽  
Diabetic Rats ◽  
Β Cells ◽  
Β Cell ◽  
Antioxidative Effect ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Pancreatic Insulin ◽  
Treatment Of Diabetes ◽  
Old Rats

Many medicinal plants are widely grown in South- and Southeast Asia countries. Some of them are traditionally used for treatment of diabetes mellitus such as Andrographispaniculata and Centellaasiatica. In the study, we provided fractionated-extracts of A. paniculata and C. asiatica to increase the concentration of their active compounds and eliminate unexpected substances. The aim of the study was to evaluate the antidiabetes effect of the combination of their fractionated-extracts in male neonatal streptozotocin (STZ)-induced diabetic rats. In the study, diabetes was injected intraperitoneally 90mg.kg-1 BWSTZ  to two day-old rats. At the age of three months, the rats were administered with the combination of both fractionated-extracts for 14 consecutive days. We evaluated antidiabetes with parameters of blood glucose levels, morphology of pancreatic islet, β-cell density as well as immunohistochemical pancreatic insulin. The levels of MDA, SOD and GPx were also determined about oxidative stress change after treatment with the combination. In the study, the combination succeeded to lower the blood glucose level in neonatal STZ-induced diabetic rats. Inline with fact, improvement of rat pancreatic islets and β cells density, as well as moderate restoration of pancreatic insulin, were observed after treatment with the combination. The substance could decrease the level of MDA, and increase the levels of SOD and GPx. In conclusion, the combination of fractionated-extracts of A. paniculata and C. asiatica exhibited potential antidiabetic effect to its antioxidative effect in male neonatal STZ-induced diabetes rats.

Development of Fetal Sheep Pancreas after Transplantation into Athymic Mice

1996 ◽  
Vol 5 (4) ◽  
pp. 483-489 ◽  
Author(s):  
Bernard E. Tuch ◽  
Jocelyn C. Madrid
Keyword(s):  
Blood Glucose ◽  
Endocrine Cells ◽  
Human Pancreas ◽  
Athymic Mice ◽  
Fetal Sheep ◽  
Glucose Levels ◽  
Endocrine Differentiation ◽  
Blood Glucose Levels ◽  
And Function ◽  
Potential Use

The capacity of the fetal sheep pancreas to grow and function when transplanted into athymic mice was examined to determine whether this source of tissue might be of potential use in reversing diabetes. For this purpose fetal sheep pancreases were obtained in the period between 50 days of gestation and fullterm (148 days). Explants (1 mm3) in organ culture secreted insulin for at least 7 days, but in steadily diminishing amounts. Acute exposure to arginine (10 mM) and theophylline (10 mM), but not glucose (20 mM), calcium chloride (10 mM), and sodium butyrate (10 mM), caused acute secretion of insulin. Explants survived for many months when grafted beneath the renal capsule of athymic mice, but their growth was less, the epithelial-like component smaller, and the percentage of endocrine cells (31 ± 5%) fewer than the case of transplanted fetal human pancreas. The β cell was the predominant endocrine cell in the ungrafted fetal sheep pancreas. In the transplanted fetal sheep pancreas this was not so, the α and PP cells being dominant—β:α:S:PP = 3:14:3:11. This pattern was unchanged when the recipient mice were hyperglycemic—β:α:δ:PP = 4:13:4:28, with no reduction of blood glucose levels being observed for up to 4 mo after transplantation. Altering the site of transplantation to the spleen or liver did not improve survival of the endocrine cells. Fetal sheep pancreatic explants when transplanted into athymic rats failed to survive. Thus, although the unusual pattern of endocrine differentiation in fetal sheep pancreas transplanted into athymic mice makes it an interesting model for further studies of fetal development, it is not of benefit in normalizing the blood glucose levels of the recipients.

Compensatory Recovery of Blood Glucose Levels in KKAy Mice Fed a High-Fat Diet: Insulin-Sparing Effects of PACAP Overexpression in β Cells

2012 ◽  
Vol 48 (3) ◽  
pp. 647-653 ◽  
Author(s):  
Yusuke Sakurai ◽  
Hiroaki Inoue ◽  
Norihito Shintani ◽  
Akihiro Arimori ◽  
Ken-ichi Hamagami ◽  
...  
Keyword(s):  
Blood Glucose ◽  
High Fat Diet ◽  
High Fat ◽  
Β Cells ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Kkay Mice

scholarly journals Enhanced Differentiation of Human Pluripotent Stem Cells into Pancreatic Endocrine Cells in 3D Culture by Inhibition of Focal Adhesion Kinase

2020 ◽  
Author(s):  
Xiaofang Liu ◽  
Jinhua Qin ◽  
Mingyang Chang ◽  
Shuyong Wang ◽  
Yali Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Drug Discovery ◽  
Pluripotent Stem Cells ◽  
Endocrine Cells ◽  
3D Culture ◽  
Β Cell ◽  
Connexin 36 ◽  
Insulin Producing Cells ◽  
Pancreatic Endocrine Cells

Abstract Background The generation insulin-producing cells from human pluripotent stem cells (hPSC) in vitro would be useful for drug discovery and cell therapy in diabetes. Three-dimensional (3D) culture is important for the acquisition of mature insulin-producing cells from hPSC, but the mechanism by which 3D culture promoted β cell maturation is poorly understood.Methods We established a stepwise differentiation method to induce human embryonic stem cells (hESC) into mature monohormonal pancreatic endocrine cells (PEC) at high efficiency, with the last maturation stage in 3D culture. To make a comprehensive comparison between 2D culture and 3D culture, we examined gene expression, pancreatic-specific markers and functional characteristics of 2D culture-induced PEC and 3D culture-induced PEC. And the mechanisms was discussed from the perspective of cell-cell and cell-extracellular matrix interactions which are fundamentally different between 2D and 3D culture.Results Expression of pancreatic endocrine-specific transcription factors PDX1, NKX6.1, NGN3, ISL1, PAX6 and hormones INS, GCG, SST were significantly increased in 3D culture-induced PEC. 3D culture gave rise to monohormonal endocrine cells, while 2D culture-induced PEC co-expressed INS and GCG or INS and SST, and some cells even expressed all three hormones. We found that FAK phosphorylation level was significantly downregulated in 3D culture-induced PEC, and treatment with a selective FAK inhibitor PF-537228 could improve the expression of β cell-specific transcription factors. We further demonstrated that 3D culture may promote endocrine commitment by limiting FAK-dependent activation of the Smad2/3 pathway. Moreover, the expression of gap junction protein Connexin 36 is much higher in 3D culture-induce PEC than 2D culture-induced PEC, and inhibition of FAK pathway in 2D culture increased Connexin 36 expression.Conclusion We developed a differentiation strategy to induce monohormonal mature PEC from hPSC and found limited FAK-dependent activation of the Smad2/3 pathway and unregulated expression of Connexin 36 in 3D culture-induced PEC. This study has important implications for the generation of mature, functional β-cells for drug discovery and cell transplantation therapy in diabetes, and sheds new light on the signaling events that regulate endocrine specification.

scholarly journals Insulin Knockout Mice Have Extended Survival but Volatile Blood Glucose Levels on Leptin Therapy

Endocrinology ◽  
2015 ◽  
Vol 157 (3) ◽  
pp. 1007-1012 ◽  
Author(s):  
Ursula H. Neumann ◽  
Heather C. Denroche ◽  
Majid Mojibian ◽  
Scott D. Covey ◽  
Timothy J. Kieffer
Keyword(s):  
Blood Glucose ◽  
Plasma Corticosterone ◽  
Β Cell ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Immune Mediated ◽  
Reduce Blood Glucose ◽  
Fasting Hypoglycemia ◽  
Extended Survival

Abstract Leptin can reverse hyperglycemia in rodent models of type 1 diabetes. However, these models have used chemical or immune mediated β-cell destruction where insulin depletion is incomplete. Thus it is unknown which actions of leptin are entirely insulin independent, versus those which require insulin. To directly assess this we maximized blockage of insulin action using an insulin receptor antagonist in combination with streptozotocin-diabetic mice; leptin treatment was still able to reduce blood glucose. Next, we leptin-treated adult insulin knockout (InsKO) mice. Remarkably, leptin-treated InsKO mice were viable for up to 3 weeks without insulin therapy. Leptin treatment reduced plasma corticosterone, glucagon, β-hydroxybutyrate, triglycerides, cholesterol, fatty acids and glycerol. However, leptin-treated InsKO mice exhibited overt fed hyperglycemia and severe fasting hypoglycemia. Therefore, leptin can normalize many metabolic parameters in the complete absence of insulin, but blood glucose levels are volatile and the length of survival finite.

Blood Glucose Levels and Mortality in Patients With Sepsis: Dose–Response Analysis of Observational Studies

2019 ◽  
Vol 36 (2) ◽  
pp. 182-190
Author(s):  
Wen Wang ◽  
Wenwen Chen ◽  
Yanmei Liu ◽  
Ling Li ◽  
Sheyu Li ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Cohort Studies ◽  
Dose Response ◽  
Meta Analysis ◽  
Current Evidence ◽  
Response Analysis ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Diabetes Status

Background: We undertook a systematic review and meta-analysis to investigate the relationship between blood glucose levels and mortality in patients with sepsis. Methods: Medline and EMBASE were searched from inception to April 8, 2018. Cohort studies or case–control studies reported the association between blood glucose and mortality in patients with sepsis were selected. Study characteristics, baseline characteristics, definition of hyperglycemia, and outcomes of interest were extracted. We performed a dose–response meta-analysis to assess the effect of blood glucose level on mortality. We also conducted meta-analysis for patients with or without diabetes separately. Results: Ten cohort studies involving 26 429 patients were included, of which 5 were prospective studies and 5 retrospective studies. Dose–response analysis showed that the effect of blood glucose on mortality may differ in patients with versus without diabetes. There was a U-shaped relationship for patients with diabetes and a J-shaped relationship for patients without diabetes, with blood glucose at 145 to 155 mg/dL corresponding to lowest mortality both in patients with and without diabetes. Conclusions: Current evidence suggested U-shaped relationship between blood glucose and mortality in all patients irrespective of their diabetes status. Diabetic patients with blood glucose below 145 mg/dL may have poorer prognosis compared to patients without established diabetes.

scholarly journals THE EFFECT OF AMINO ACID COMPOUNDS IN FERMENTED SOYBEANS AGAINST FIBROBLAST GROWTH FACTOR IN MICE PANCREATIC β-CELLS FIGURES

2018 ◽  
Vol 11 (9) ◽  
pp. 157
Author(s):  
Surya Dharma ◽  
Dedy Almasdy ◽  
Dwisari Dillasamola ◽  
Roslinda Rasyid ◽  
Dianty Dwi Wahyuni ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Fibroblast Growth ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Experimental Animals ◽  
Glucose Levels ◽  
Blood Glucose Levels

Objective: The aim of this study is to determine the effect of the amino acid compound in fermented soybeans against fibroblast growth factor (FGF) in mice’s pancreatic β-cell figures. This study was also done to know the effect of given combination of fertilized egg whites powder with tempe (Indonesian conventional food and the fermentation product of soybeans fermentation) in a dose of 7250 mg/kg.Methods: All of the experimental animals pancreases were designed to be damaged by given alloxan in a dose of 150 mg/kg, except for the negative control group without anything given. The experimental animals were divided into 7 groups which consist of the negative control group, positive control group, and the rests 5 group of FGF test preparation in dosages of 100; 140; 200; 300; and 425 mg/kg combined with fermented soybeans in a dose 7250 mg/kg. This experiment was conducted for 21 days, observed at 7th, 14th, and 21st day. The data analysis used is a statistical test of one-way analysis of variance (ANOVA) and two-way ANOVA.Results: The result showed a significant decrease in blood glucose levels (p<0.05) in mice for all treatments when compared with positive controls. From the result of the histopathologic examination, pancreatic β-cells improve utterly close to the control condition (-). In the qualitative immunohistochemical examination, there was a difference in the stained pancreatic β-cells marked by yellow density. Meanwhile, the quantitative observation did not show any improvement against normal condition control (-) (p<0.05).Conclusion: The combination of egg whites and fermented soybean significantly decreased the blood glucose levels, and the occurrence of the Langerhans island cells was nearly normal.

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