scholarly journals Aquaporin 1 Is Important for Maintaining Secretory Granule Biogenesis in Endocrine Cells

2008 ◽  
Vol 22 (8) ◽  
pp. 1924-1934 ◽  
Author(s):  
Irina Arnaoutova ◽  
Niamh X. Cawley ◽  
Nimesh Patel ◽  
Taeyoon Kim ◽  
Trushar Rathod ◽  
...  
Keyword(s):  
Secretory Granule ◽  
Endocrine Cells ◽  
Cell Function ◽  
Hormone Secretion ◽  
Prohormone Convertase ◽  
Protein Levels ◽  
Prohormone Convertase 1 ◽  
Aqp1 Expression ◽  
Low Levels ◽  
Made In

Abstract Aquaporins (AQPs), a family of water channels expressed in epithelial cells, function to transport water in a bidirectional manner to facilitate transepithelial fluid absorption and secretion. Additionally, AQP1 and AQP5 are found in pancreatic zymogen granules and synaptic vesicles and are involved in vesicle swelling and exocytosis in exocrine cells and neurons. Here, we show AQP1 is in dense-core secretory granule (DCSG) membranes of endocrine tissue: pituitary and adrenal medulla. The need for AQP1 in endocrine cell function was examined by stable transfection of AQP1 antisense RNA into AtT20 cells, a pituitary cell line, to down-regulate AQP1 expression. These AQP1-deficient cells showed more than 60% depletion of DCSGs and significantly decreased DCSG protein levels, including proopiomelanocotin/pro-ATCH and prohormone convertase 1/3, but not non-DCSG proteins. Pulse-chase studies revealed that whereas DCSG protein synthesis was unaffected, approximately 50% of the newly synthesized proopiomelanocortin was degraded within 1 h. Low levels of ACTH were released upon stimulation, indicating that the small number of DCSGs that were made in the presence of the residual AQP1 were functionally competent for exocytosis. Analysis of anterior pituitaries from AQP1 knockout mice showed reduced prohormone convertase 1/3, carboxypeptidase E, and ACTH levels compared to wild-type mice demonstrating that our results observed in AtT20 cells can be extended to the animal model. Thus, AQP1 is important for maintaining DCSG biogenesis and normal levels of hormone secretion in pituitary endocrine cells.

scholarly journals Ins1-Cre and Ins1-CreER Gene Replacement Alleles Are Susceptible To Silencing By DNA Hypermethylation

Endocrinology ◽  
2020 ◽  
Vol 161 (8) ◽  
Author(s):  
Elham Mosleh ◽  
Kristy Ou ◽  
Matthew W Haemmerle ◽  
Teguru Tembo ◽  
Andrew Yuhas ◽  
...  
Keyword(s):  
Beta Cell ◽  
Endocrine Cells ◽  
Target Genes ◽  
Cell Function ◽  
Gene Replacement ◽  
Wild Type ◽  
Dna Hypermethylation ◽  
Gene Ablation ◽  
Low Levels ◽  
The Brain

Abstract Targeted gene ablation studies of the endocrine pancreas have long suffered from suboptimal Cre deleter strains. In many cases, Cre lines purportedly specific for beta cells also displayed expression in other islet endocrine cells or in a subset of neurons in the brain. Several pancreas and endocrine Cre lines have experienced silencing or mosaicism over time. In addition, many Cre transgenic constructs were designed to include the hGH mini-gene, which by itself increases beta-cell replication and decreases beta-cell function. More recently, driver lines with Cre or CreER inserted into the Ins1 locus were generated, with the intent of producing β cell-specific Cre lines with faithful recapitulation of insulin expression. These lines were bred in multiple labs to several different mouse lines harboring various lox alleles. In our hands, the ability of the Ins1-Cre and Ins1-CreER lines to delete target genes varied from that originally reported, with both alleles displaying low levels of expression, increased levels of methylation compared to the wild-type allele, and ultimately inefficient or absent target deletion. Thus, caution is warranted in the interpretation of results obtained with these genetic tools, and Cre expression and activity should be monitored regularly when using these lines.

scholarly journals Upregulated insulin secretion in insulin-resistant mice: evidence of increased islet GLP1 receptor levels and GPR119-activated GLP1 secretion

2013 ◽  
Vol 2 (2) ◽  
pp. 69-78 ◽  
Author(s):  
L Ahlkvist ◽  
K Brown ◽  
B Ahrén
Keyword(s):  
Cell Function ◽  
Hormone Secretion ◽  
Glucagon Secretion ◽  
Β Cell ◽  
Insulin Resistant ◽  
Protein Levels ◽  
Islet Hormone ◽  
Β Cell Function ◽  
Glucagon Like Peptide 1 ◽  
Insulin Responses

We previously demonstrated that the overall incretin effect and the β-cell responsiveness to glucagon-like peptide-1 (GLP1) are increased in insulin-resistant mice and may contribute to the upregulated β-cell function. Now we examined whether this could, first, be explained by increased islet GLP1 receptor (GLP1R) protein levels and, secondly, be leveraged by G-protein-coupled receptor 119 (GPR119) activation, which stimulates GLP1 secretion. Female C57BL/6J mice, fed a control (CD, 10% fat) or high-fat (HFD, 60% fat) diet for 8 weeks, were anesthetized and orally given a GPR119 receptor agonist (GSK706A; 10 mg/kg) or vehicle, followed after 10 min with gavage with a liquid mixed meal (0.285 kcal). Blood was sampled for determination of glucose, insulin, intact GLP1, and glucagon, and islets were isolated for studies on insulin and glucagon secretion and GLP1R protein levels. In HFD vs CD mice, GPR119 activation augmented the meal-induced increase in the release of both GLP1 (AUCGLP1 81±9.6 vs 37±6.9 pM×min, P=0.002) and insulin (AUCINS 253±29 vs 112±19 nM×min, P<0.001). GPR119 activation also significantly increased glucagon levels in both groups (P<0.01) with, however, no difference between the groups. By contrast, GPR119 activation did not affect islet hormone secretion from isolated islets. Glucose elimination after meal ingestion was significantly increased by GPR119 activation in HFD mice (0.57±0.04 vs 0.43±0.03% per min, P=0.014) but not in control mice. Islet GLP1R protein levels was higher in HFD vs CD mice (0.8±0.1 vs 0.5±0.1, P=0.035). In conclusion, insulin-resistant mice display increased islet GLP1R protein levels and augmented meal-induced GLP1 and insulin responses to GPR119 activation, which results in increased glucose elimination. We suggest that the increased islet GLP1R protein levels together with the increased GLP1 release may contribute to the upregulated β-cell function in insulin resistance.

scholarly journals Involvement of calpain and synaptotagmin Ca2+ sensors in hormone secretion from excitable endocrine cells

2006 ◽  
Vol 190 (3) ◽  
pp. R1-R7 ◽  
Author(s):  
Ebun Aganna ◽  
Jacky M Burrin ◽  
Graham A Hitman ◽  
Mark D Turner
Keyword(s):  
Protease Inhibitor ◽  
Endocrine Cells ◽  
Hormone Secretion ◽  
Cysteine Proteases ◽  
Cysteine Protease Inhibitor ◽  
Gh3 Cells ◽  
Pituitary Cells ◽  
Calpain 10 ◽  
Stimulus Secretion Coupling ◽  
Low Levels

The requirement for Ca2+ to regulate hormone secretion from endocrine cells is long established, but the precise function of Ca2+ sensors in stimulus–secretion coupling remains unclear. In the current study, we examined the expression of calpain and synaptotagmin in INS-1 pancreatic and GH3 and AtT20 pituitary cells, and investigated the sensitivity of hormone secretion from these cells to inhibition of the calpain family of cysteine proteases. Little difference in expression of μ-calpain was observed between the different endocrine cells. However, AtT20 cells did exhibit an extremely low abundance of both m-calpain and the 54 kDa isoform of calpain-10 relative to their expression in INS-1 and GH3 cells. Interestingly, secretagog-stimulated secretion from both INS-1 and GH3 cells was completely abolished following pre-incubation with the cysteine protease inhibitor E64, whereas stimulated secretion from AtT20 cells was modest and completely insensitive to E64 inhibition. These results are in stark contrast to synaptotagmin data. Synaptotagmin expression in AtT20 cells is abundant, whereas INS-1 cells express extremely low levels of this Ca2+ sensor, relative to the pituitary cells. We hypothesize that the expression pattern of calpain and synaptotagmin isoforms may reflect alternative mechanisms of stimulus–secretion coupling in excitable endocrine cells.

scholarly journals Effects of gypenosides on enteroendocrine L-cell function and GLP-1 secretion

2020 ◽  
Author(s):  
Chinmai Patibandla ◽  
Erin Campbell ◽  
Xinhua Shu ◽  
Angus M Shaw ◽  
Sharron Dolan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Function ◽  
Postprandial Glucose ◽  
Prohormone Convertase ◽  
Antioxidant Gene ◽  
Protein Levels ◽  
L Cells ◽  
Prohormone Convertase 2

AbstractGlucagon-like peptide 1 (GLP-1) is an incretin hormone produced in gut L-cells, which regulates postprandial glucose-dependent insulin secretion, also known as the incretin effect. GLP-1 secretion may be reduced in type 2 diabetes mellitus, impacting on glycaemic regulation. Thus, methods to enhance endogenous GLP-1 secretion by use of natural GLP-1 secretagogues may improve glucose control in diabetes. Gypenosides (GYP) extracted from the plant Gynostemma Pentaphyllum (Jiaogulan) are known for their glucose-lowering effects both in vitro and in vivo, although their effect on GLP-1 secretion is unknown. Our results showed that GYP enhanced cell viability and significantly upregulated antioxidant gene Nrf2, Cat and Ho-1 expression. GYP did not affect glucokinase expression but downregulated proglucagon gene expression over 24h, although, cellular GLP-1 content was unchanged. Prohormone convertase 1 (Pcsk1) gene expression was unchanged by GYP over 24h, although protein levels were significantly downregulated, while prohormone convertase 2 (Pcsk2) mRNA and protein levels were significantly upregulated. Acute exposure to gypenosides enhanced calcium uptake and GLP-1 release from GLUTag cells both at low and high glucose concentrations. These results suggest that anti-diabetic properties of gypenosides are partly linked to their ability to stimulate GLP-1 secretion. Gypenosides enhance antioxidant gene expression and may protect L-cells from excess oxidative stress.

Induction of ER stress by variants of the prohormone convertase 1 (PCSK1)-gene

2013 ◽  
Vol 8 (S 01) ◽  
Author(s):  
S Behrendt ◽  
D Löffler ◽  
R Tauscher ◽  
A Körner
Keyword(s):  
Er Stress ◽  
Prohormone Convertase ◽  
Prohormone Convertase 1 ◽  
Pcsk1 Gene

Immunologic Studies of Antithrombin III Heparin Cofactor in the Newborn

1978 ◽  
Vol 39 (03) ◽  
pp. 624-630 ◽  
Author(s):  
W E Hathaway ◽  
L L Neumann ◽  
C A Borden ◽  
L J Jacobson
Keyword(s):  
Gestational Age ◽  
Antithrombin Iii ◽  
Newborn Infants ◽  
Term Infant ◽  
Sick Newborn ◽  
At Iii ◽  
Thrombotic Complications ◽  
Low Levels ◽  
Collection Methods ◽  
Made In

SummarySerial quantitative immunoelectrophoretic (IE) measurements of antithrombin III heparin cofactor (AT III) were made in groups of well and sick newborn infants classified by gestational age. Collection methods (venous vs. capillary) did not influence the results; serum IE measurements were comparable to AT III activity by a clotting method. AT III is gestational age-dependent, increasing from 28.7% of normal adult values at 28-32 weeks to 50.9% at 37-40 weeks, and shows a gradual increase to term infant levels (57.4%) by 3-4 weeks of age. Infants with the respiratory distress syndrome (RDS) show lower levels of AT III in the 33-36 week group, 22% vs. 44% and in the 37-40 week group, 33.6% vs. 50.9%, than prematures without RDS. Infants of 28-32 week gestational age had only slight differences, RDS = 24%, non-RDS = 28.7%. The lowest levels of AT III were seen in patients with RDS complicated by disseminated intravascular coagulation and those with necrotizing enterocolitis. Crossed IE on representative infants displayed a consistent pattern which was identical to adult controls except for appropriate decreases in the amplitude of the peaks. The thrombotic complications seen in the sick preterm infant may be related to the low levels of AT III.

ABATEMENT OF ANTICANCER DRUGS VIA ELECTROCHEMICAL OXIDATION PROCESS: A REVIEW

2020 ◽  
pp. 1-4
Author(s):  
CHARULATA SIVODIA ◽  
ALOK SINHA
Keyword(s):  
Anticancer Drugs ◽  
Cell Function ◽  
Electrochemical Techniques ◽  
Aquatic Organisms ◽  
Pharmaceutical Drugs ◽  
Cytostatic Drugs ◽  
Cancerous Cell ◽  
Pharmaceutical Removal ◽  
Mutagenic Effects ◽  
Made In

The advancement made in biomedical industry upsurges the consumption rate of pharmaceutical drugs. The lack of proper monitoring and regulation methods leads to the unregulated discharge of pharmaceuticals in wastewater, where it can affect the aquatic organisms. Anticancer drugs are also known as cytostatic drugs mainly used for the treatment of cancer by disrupting the cell function and prevent multiplication of cancerous cell. Therefore, anticancer drugs are suspected to pose potential risk on environment by influencing mutagenic effects on the cells of aquatic organisms. An extensive research has been already made in the field of pharmaceutical removal, however their application on the removal of anticancer drugs is limited. This review paper elucidates about different electrochemical techniques for the mitigation of cytostatic drugs.

O8 Une déficience partielle en prohormone convertase 1 confère une augmentation du risque de l’obésité

2010 ◽  
Vol 36 ◽  
pp. A2-A3
Author(s):  
H. Choquet ◽  
J. Creemers ◽  
M. Pigeyre ◽  
V. Vatin ◽  
B. Balkau ◽  
...  
Keyword(s):  
Prohormone Convertase ◽  
Prohormone Convertase 1
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