Synaptotagmin 4 Regulates Pancreatic β Cell Maturation by Modulating the Ca2+ Sensitivity of Insulin Secretion Vesicles

AbstractThe apelin receptor (Aplnr) and its ligands, Apelin and Apela, contribute to metabolic control. The insulin resistance associated with pregnancy is accommodated by an expansion of pancreatic β-cell mass (BCM) and increased insulin secretion, involving the proliferation of insulin-expressing, glucose transporter 2-low (Ins+Glut2LO) progenitor cells. We examined changes in the apelinergic system during normal mouse pregnancy and in pregnancies complicated by glucose intolerance with reduced BCM. Expression of Aplnr, Apelin and Apela was quantified in Ins+Glut2LO cells isolated from mouse pancreata and found to be significantly higher than in mature β-cells by DNA microarray and qPCR. Apelin was localized to most β-cells by immunohistochemistry although Aplnr was predominantly associated with Ins+Glut2LO cells. Aplnr-staining cells increased three- to four-fold during pregnancy being maximal at gestational days (GD) 9–12 but were significantly reduced in glucose intolerant mice. Apelin-13 increased β-cell proliferation in isolated mouse islets and INS1E cells, but not glucose-stimulated insulin secretion. Glucose intolerant pregnant mice had significantly elevated serum Apelin levels at GD 9 associated with an increased presence of placental IL-6. Placental expression of the apelinergic axis remained unaltered, however. Results show that the apelinergic system is highly expressed in pancreatic β-cell progenitors and may contribute to β-cell proliferation in pregnancy.

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Effects of pharmacological inhibition of NADPH oxidase or iNOS on pro-inflammatory cytokine, palmitic acid or H2O2-induced mouse islet or clonal pancreatic β-cell dysfunction

Bioscience Reports ◽

10.1042/bsr20090138 ◽

2010 ◽

Vol 30 (6) ◽

pp. 445-453 ◽

Cited By ~ 41

Author(s):

Marta Michalska ◽

Gabriele Wolf ◽

Reinhard Walther ◽

Philip Newsholme

Keyword(s):

Fatty Acids ◽

Insulin Secretion ◽

Nadph Oxidase ◽

Inflammatory Cytokine ◽

Pancreatic Β Cell ◽

Β Cells ◽

Β Cell ◽

Cell Dysfunction ◽

Mouse Islets ◽

Pro Inflammatory Cytokines

Various pancreatic β-cell stressors including cytokines and saturated fatty acids are known to induce oxidative stress, which results in metabolic disturbances and a reduction in insulin secretion. However, the key mechanisms underlying dysfunction are unknown. We investigated the effects of prolonged exposure (24 h) to pro-inflammatory cytokines, H2O2 or PA (palmitic acid) on β-cell insulin secretion, ATP, the NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) component p47phox and iNOS (inducible nitric oxide synthase) levels using primary mouse islets or clonal rat BRIN-BD11 β-cells. Addition of a pro-inflammatory cytokine mixture [IL-1β (interleukin-1β), TNF-α (tumour necrosis factor-α) and IFN-γ (interferon-γ)] or H2O2 (at sub-lethal concentrations) inhibited chronic (24 h) levels of insulin release by at least 50% (from islets and BRIN-BD11 cells), while addition of the saturated fatty acid palmitate inhibited acute (20 min) stimulated levels of insulin release from mouse islets. H2O2 decreased ATP levels in the cell line, but elevated p47phox and iNOS levels as did cytokine addition. Similar effects were observed in mouse islets with respect to elevation of p47phox and iNOS levels. Addition of antioxidants SOD (superoxide dismutase), Cat (catalase) and NAC (N-acetylcysteine) attenuated H2O2 or the saturated fatty acid palmitate-dependent effects, but not cytokine-induced dysfunction. However, specific chemical inhibitors of NADPH oxidase and/or iNOS appear to significantly attenuate the effects of cytokines, H2O2 or fatty acids in islets. While pro-inflammatory cytokines are known to increase p47phox and iNOS levels in β-cells, we now report that H2O2 can increase levels of the latter two proteins, suggesting a key role for positive-feedback redox sensitive regulation of β-cell dysfunction.

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Improvement of insulin secretion and pancreatic β-cell function in streptozotocin-induced diabetic rats treated with Aloe vera extract

Pharmacognosy Research ◽

10.4103/pr.pr_75_17 ◽

2017 ◽

Vol 9 (5) ◽

pp. 99 ◽

Cited By ~ 14

Author(s):

Ayesha Noor ◽

S Gunasekaran ◽

MA Vijayalakshmi

Keyword(s):

Insulin Secretion ◽

Cell Function ◽

Aloe Vera ◽

Diabetic Rats ◽

Pancreatic Β Cell ◽

Β Cell ◽

Β Cell Function

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Effect of Serum Zinc and Copper Levels on Insulin Secretion, Insulin Resistance and Pancreatic β cell Dysfunction in US Adults: Findings from the National Health and Nutrition Examination Survey (NHANES) 2011-2012

Diabetes Research and Clinical Practice ◽

10.1016/j.diabres.2020.108627 ◽

2020 ◽

pp. 108627

Author(s):

Ravi Kant ◽

Vipin Verma ◽

Siddharth Patel ◽

Rashmi Chandra ◽

Rahul Chaudhary ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Secretion ◽

National Health ◽

Serum Zinc ◽

Nutrition Examination Survey ◽

Pancreatic Β Cell ◽

Β Cell ◽

Cell Dysfunction ◽

Health And Nutrition

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

Plants ◽

10.3390/plants9091087 ◽

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.

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