scholarly journals Syntaxin 4 Expression in Pancreatic β-Cells Promotes Islet Function and Protects Functional β-Cell Mass

Diabetes ◽  
2018 ◽  
Vol 67 (12) ◽  
pp. 2626-2639 ◽  
Author(s):  
Eunjin Oh ◽  
Miwon Ahn ◽  
Solomon Afelik ◽  
Thomas C. Becker ◽  
Bart O. Roep ◽  
...  
Keyword(s):  
Cell Mass ◽  
Islet Function ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Syntaxin 4

Autophagy in health and disease. 4. The role of pancreatic β-cell autophagy in health and diabetes

2010 ◽  
Vol 299 (1) ◽  
pp. C1-C6 ◽  
Author(s):  
Yoshio Fujitani ◽  
Takashi Ueno ◽  
Hirotaka Watada
Keyword(s):  
Cell Mass ◽  
Normal Function ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Ubiquitinated Proteins ◽  
Evolutionarily Conserved ◽  
Health And Disease ◽  
Cellular Stresses

Autophagy is an evolutionarily conserved machinery for degradation and recycling of various cytoplasmic components such as long-lived proteins and organelles. In pancreatic β-cells, as in most other cells, autophagy is also important for the low basal turnover of ubiquitinated proteins and damaged organelles under normal conditions. Insulin resistance results in upregulation of autophagic activity in β-cells. Induced autophagy in β-cells plays a pivotal role in the adaptive expansion of β-cell mass. Nevertheless, it is not clear whether autophagy is protective or detrimental in response to cellular stresses in β-cells. In this review, we describe the crucial roles of autophagy in normal function of β-cells and discuss how dysfunction of the autophagic machinery could lead to the development of diabetes mellitus.

Arachidonic acid fights palmitate: new insights into fatty acid toxicity in β-cells

2010 ◽  
Vol 120 (5) ◽  
pp. 179-181 ◽  
Author(s):  
Henrik Ortsäter
Keyword(s):  
Type 2 Diabetes ◽  
Arachidonic Acid ◽  
Fatty Acid ◽  
Saturated Fatty Acids ◽  
Cell Mass ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Self Protection

Saturated fatty acids are toxic to pancreatic β-cells. By inducing apoptosis, they contribute to a decrease in β-cell mass, a hallmark of Type 2 diabetes. In the present issue of Clinical Science, Keane and co-workers show that the polyunsaturated fatty acid arachidonic acid protects the β-cell against the toxic effects of palmitate. As Type 2 diabetes is characterized by subclinical inflammation, and arachidonic acid and metabolites thereof are produced during states of inflammation, it is possible that pancreatic β-cells use arachidonic acid as a compound for self-protection.

scholarly journals Trefoil Factor 2 Promotes Cell Proliferation in Pancreatic β-Cells through CXCR-4-Mediated ERK1/2 Phosphorylation

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 54-64 ◽  
Author(s):  
Kazuki Orime ◽  
Jun Shirakawa ◽  
Yu Togashi ◽  
Kazuki Tajima ◽  
Hideaki Inoue ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Mass ◽  
Brdu Incorporation ◽  
Trefoil Factor ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Min6 Cells ◽  
Trefoil Factor 2 ◽  
Chemokine Receptor 4

Decreased β-cell mass is a hallmark of type 2 diabetes, and therapeutic approaches to increase the pancreatic β-cell mass have been expected. In recent years, gastrointestinal incretin peptides have been shown to exert a cell-proliferative effect in pancreatic β-cells. Trefoil factor 2 (TFF2), which is predominantly expressed in the surface epithelium of the stomach, plays a role in antiapoptosis, migration, and proliferation. The TFF family is expressed in pancreatic β-cells, whereas the role of TFF2 in pancreatic β-cells has been obscure. In this study, we investigated the mechanism by which TFF2 enhances pancreatic β-cell proliferation. The effects of TFF2 on cell proliferation were evaluated in INS-1 cells, MIN6 cells, and mouse islets using an adenovirus vector containing TFF2 or a recombinant TFF2 peptide. The forced expression of TFF2 led to an increase in bromodeoxyuridine (BrdU) incorporation in both INS-1 cells and islets, without any alteration in insulin secretion. TFF2 significantly increased the mRNA expression of cyclin A2, D1, D2, D3, and E1 in islets. TFF2 peptide increased ERK1/2 phosphorylation and BrdU incorporation in MIN6 cells. A MAPK kinase inhibitor (U0126) abrogated the TFF2 peptide-mediated proliferation of MIN6 cells. A CX-chemokine receptor-4 antagonist also prevented the TFF2 peptide-mediated increase in ERK1/2 phosphorylation and BrdU incorporation in MIN6 cells. These results indicated that TFF2 is involved in β-cell proliferation at least partially via CX-chemokine receptor-4-mediated ERK1/2 phosphorylation, suggesting TFF2 may be a novel target for inducing β-cell proliferation.

scholarly journals Gut Metabolite Trimethylamine N-Oxide Protects INS-1 β-Cell and Rat Islet Function under Diabetic Glucolipotoxic Conditions

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1892
Author(s):  
Emily S. Krueger ◽  
Joseph L. Beales ◽  
Kacie B. Russon ◽  
Weston S. Elison ◽  
Jordan R. Davis ◽  
...  
Keyword(s):  
Cell Function ◽  
Cell Mass ◽  
Caloric Intake ◽  
Islet Function ◽  
Β Cells ◽  
Β Cell ◽  
Granule Formation ◽  
Β Cell Function ◽  
Molecular Effects ◽  
And Function

Serum accumulation of the gut microbial metabolite trimethylamine N-oxide (TMAO) is associated with high caloric intake and type 2 diabetes (T2D). Impaired pancreatic β-cell function is a hallmark of diet-induced T2D, which is linked to hyperglycemia and hyperlipidemia. While TMAO production via the gut microbiome-liver axis is well defined, its molecular effects on metabolic tissues are unclear, since studies in various tissues show deleterious and beneficial TMAO effects. We investigated the molecular effects of TMAO on functional β-cell mass. We hypothesized that TMAO may damage functional β-cell mass by inhibiting β-cell viability, survival, proliferation, or function to promote T2D pathogenesis. We treated INS-1 832/13 β-cells and primary rat islets with physiological TMAO concentrations and compared functional β-cell mass under healthy standard cell culture (SCC) and T2D-like glucolipotoxic (GLT) conditions. GLT significantly impeded β-cell mass and function by inducing oxidative and endoplasmic reticulum (ER) stress. TMAO normalized GLT-mediated damage in β-cells and primary islet function. Acute 40µM TMAO recovered insulin production, insulin granule formation, and insulin secretion by upregulating the IRE1α unfolded protein response to GLT-induced ER and oxidative stress. These novel results demonstrate that TMAO protects β-cell function and suggest that TMAO may play a beneficial molecular role in diet-induced T2D conditions.

Ablation of PDK1 in pancreatic β cells induces diabetes as a result of loss of β cell mass

2006 ◽  
Vol 38 (5) ◽  
pp. 589-593 ◽  
Author(s):  
Naoko Hashimoto ◽  
Yoshiaki Kido ◽  
Tohru Uchida ◽  
Shun-ichiro Asahara ◽  
Yutaka Shigeyama ◽  
...  
Keyword(s):  
Cell Mass ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

scholarly journals The Plasticity of Pancreatic β-Cells

Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 218
Author(s):  
Norikiyo Honzawa ◽  
Kei Fujimoto
Keyword(s):  
Insulin Secretion ◽  
Progenitor Cells ◽  
Islet Cells ◽  
Cell Mass ◽  
Pancreatic Β Cell ◽  
Cell Plasticity ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Impaired Insulin

Type 2 diabetes is caused by impaired insulin secretion and/or insulin resistance. Loss of pancreatic β-cell mass detected in human diabetic patients has been considered to be a major cause of impaired insulin secretion. Additionally, apoptosis is found in pancreatic β-cells; β-cell mass loss is induced when cell death exceeds proliferation. Recently, however, β-cell dedifferentiation to pancreatic endocrine progenitor cells and β-cell transdifferentiation to α-cell was reported in human islets, which led to a new underlying molecular mechanism. Hyperglycemia inhibits nuclear translocation and expression of forkhead box-O1 (FoxO1) and induces the expression of neurogenin-3(Ngn3), which is required for the development and maintenance of pancreatic endocrine progenitor cells. This new hypothesis (Foxology) is attracting attention because it explains molecular mechanism(s) underlying β-cell plasticity. The lineage tracing technique revealed that the contribution of dedifferentiation is higher than that of β-cell apoptosis retaining to β-cell mass loss. In addition, islet cells transdifferentiate each other, such as transdifferentiation of pancreatic β-cell to α-cell and vice versa. Islet cells can exhibit plasticity, and they may have the ability to redifferentiate into any cell type. This review describes recent findings in the dedifferentiation and transdifferentiation of β-cells. We outline novel treatment(s) for diabetes targeting islet cell plasticity.

scholarly journals Nuclear Factor Y in Male Mouse pancreatic β-cells Plays a Crucial Role in Glucose Homeostasis by Regulating β-Cell Mass and Insulin Secretion

2021 ◽  
Author(s):  
Yin Liu ◽  
Siyuan He ◽  
Ruixue Zhou ◽  
Xueping Zhang ◽  
Shanshan Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
Cell Mass ◽  
Physiological Role ◽  
Nuclear Factor ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Nuclear Factor Y

Pancreatic β-cell mass and insulin secretion are determined by the dynamic change of transcription factor expression levels in response to altered metabolic demand. Nuclear factor-Y (NF-Y) is an evolutionarily conserved transcription factor playing critical roles in multiple cellular processes. However, the physiological role of NF-Y in pancreatic β-cells is poorly understood. The present study was undertaken in a conditional knockout of <i>Nf-ya</i> specifically in pancreatic β-cells (<i>Nf-ya </i>βKO) to define the essential physiological role of NF-Y in β-cells. <i>Nf-ya </i>βKO mice exhibited glucose intolerance without changes in insulin sensitivity. Reduced β-cell proliferation resulting in decreased β-cell mass was observed in these mice, which was associated with disturbed actin cytoskeleton. NF-Y-deficient β-cells also exhibited impaired insulin secretion with a reduced Ca<sup>2+</sup> influx in response to glucose, which was associated an inefficient glucose uptake into β-cells due to a decreased expression of glucose transporter 2 and a reduction in ATP production resulting from the disruption of mitochondrial integrity. This study is the first to show that NF-Y is critical for pancreatic islets homeostasis and function through regulation in β-cell proliferation, glucose uptake into β-cells, and mitochondrial energy metabolism. Modulating NF-Y expression in β-cells may therefore offer an attractive approach for therapeutic intervention.

GLP-1(28–36) improves β-cell mass and glucose disposal in streptozotocin-induced diabetic mice and activates cAMP/PKA/β-catenin signaling in β-cells in vitro

2013 ◽  
Vol 304 (12) ◽  
pp. E1263-E1272 ◽  
Author(s):  
Weijuan Shao ◽  
Zhaoxia Wang ◽  
Wilfred Ip ◽  
Yu-Ting Chiang ◽  
Xiaoquan Xiong ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Cell Line ◽  
Cell Mass ◽  
Glucose Disposal ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
In Vitro Investigation

Recent studies have demonstrated that the COOH-terminal fragment of the incretin hormone glucagon-like peptide-1 (GLP-1), a nonapeptide GLP-1(28–36)amide, attenuates diabetes and hepatic steatosis in diet-induced obese mice. However, the effect of this nonapeptide in pancreatic β-cells remains largely unknown. Here, we show that in a streptozotocin-induced mouse diabetes model, GLP-1(28–36)amide improved glucose disposal and increased pancreatic β-cell mass and β-cell proliferation. An in vitro investigation revealed that GLP-1(28–36)amide stimulates β-catenin (β-cat) Ser675 phosphorylation in both the clonal INS-1 cell line and rat primary pancreatic islet cells. In INS-1 cells, the stimulation was accompanied by increased nuclear β-cat content. GLP-1(28–36)amide was also shown to increase cellular cAMP levels, PKA enzymatic activity, and cAMP response element-binding protein (CREB) and cyclic AMP-dependent transcription factor-1 (ATF-1) phosphorylation. Furthermore, GLP-1(28–36)amide treatment enhanced islet insulin secretion and increased the growth of INS-1 cells, which was associated with increased cyclin D1 expression. Finally, PKA inhibition attenuated the effect of GLP-1(28–36)amide on β-cat Ser675 phosphorylation and cyclin D1 expression in the INS-1 cell line. We have thus revealed the beneficial effect of GLP-1(28–36)amide in pancreatic β-cells in vitro and in vivo. Our observations suggest that GLP-1(28–36)amide may exert its effect through the PKA/β-catenin signaling pathway.

scholarly journals Effects of metformin on compensatory pancreatic β-cell hyperplasia in mice fed a high-fat diet

2017 ◽  
Vol 313 (3) ◽  
pp. E367-E380 ◽  
Author(s):  
Kazuki Tajima ◽  
Jun Shirakawa ◽  
Tomoko Okuyama ◽  
Mayu Kyohara ◽  
Shunsuke Yamazaki ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cell Proliferation ◽  
High Fat Diet ◽  
Cell Mass ◽  
Mammalian Target Of Rapamycin ◽  
High Fat ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Cell Hyperplasia

Metformin has been widely used for the treatment of type 2 diabetes. However, the effect of metformin on pancreatic β-cells remains controversial. In this study, we investigated the impacts of treatment with metformin on pancreatic β-cells in a mouse model fed a high-fat diet (HFD), which triggers adaptive β-cell replication. An 8-wk treatment with metformin improved insulin resistance and suppressed the compensatory β-cell hyperplasia induced by HFD-feeding. In contrast, the increment in β-cell mass arising from 60 wk of HFD feeding was similar in mice treated with and those treated without metformin. Interestingly, metformin suppressed β-cell proliferation induced by 1 wk of HFD feeding without any changes in insulin resistance. Metformin directly suppressed glucose-induced β-cell proliferation in islets and INS-1 cells in accordance with a reduction in mammalian target of rapamycin phosphorylation. Taken together, metformin suppressed HFD-induced β-cell proliferation independent of the improvement of insulin resistance, partly via direct actions.

Sign in / Sign up

Export Citation Format

Share Document