scholarly journals Overexpression of lactate dehydrogenase A attenuates glucose-induced insulin secretion in stable MIN-6 β-cell lines

FEBS Letters ◽  
1998 ◽  
Vol 430 (3) ◽  
pp. 213-216 ◽  
Author(s):  
Chao Zhao ◽  
Guy A Rutter
Keyword(s):  
Insulin Secretion ◽  
Lactate Dehydrogenase ◽  
Cell Lines ◽  
Β Cell

Regulation of Insulin Secretion: Insights from Engineered β-cell Lines

2004 ◽  
Vol 1014 (1) ◽  
pp. 88-96 ◽  
Author(s):  
SHIMON EFRAT
Keyword(s):  
Insulin Secretion ◽  
Cell Lines ◽  
Β Cell

scholarly journals Resveratrol and curcumin enhance pancreatic β-cell function by inhibiting phosphodiesterase activity

2014 ◽  
Vol 223 (2) ◽  
pp. 107-117 ◽  
Author(s):  
Michael Rouse ◽  
Antoine Younès ◽  
Josephine M Egan
Keyword(s):  
Insulin Secretion ◽  
Cell Lines ◽  
Cell Function ◽  
Human Islets ◽  
Dependent Manner ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Pde Inhibitors ◽  
Β Cell Function

Resveratrol (RES) and curcumin (CUR) are polyphenols that are found in fruits and turmeric, and possess medicinal properties that are beneficial in various diseases, such as heart disease, cancer, and type 2 diabetes mellitus (T2DM). Results from recent studies have indicated that their therapeutic properties can be attributed to their anti-inflammatory effects. Owing to reports stating that they protect against β-cell dysfunction, we studied their mechanism(s) of action in β-cells. In T2DM, cAMP plays a critical role in glucose- and incretin-stimulated insulin secretion as well as overall pancreatic β-cell health. A potential therapeutic target in the management of T2DM lies in regulating the activity of phosphodiesterases (PDEs), which degrade cAMP. Both RES and CUR have been reported to act as PDE inhibitors in various cell types, but it remains unknown if they do so in pancreatic β-cells. In our current study, we found that both RES (0.1–10 μmol/l) and CUR (1–100 pmol/l)-regulated insulin secretion under glucose-stimulated conditions. Additionally, treating β-cell lines and human islets with these polyphenols led to increased intracellular cAMP levels in a manner similar to 3-isobutyl-1-methylxanthine, a classic PDE inhibitor. When we investigated the effects of RES and CUR on PDEs, we found that treatment significantly downregulated the mRNA expression of most of the 11 PDE isozymes, including PDE3B, PDE8A, and PDE10A, which have been linked previously to regulation of insulin secretion in islets. Furthermore, RES and CUR inhibited PDE activity in a dose-dependent manner in β-cell lines and human islets. Collectively, we demonstrate a novel role for natural-occurring polyphenols as PDE inhibitors that enhance pancreatic β-cell function.

scholarly journals Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal β-cell lines

2011 ◽  
Vol 435 (1) ◽  
pp. 277-284 ◽  
Author(s):  
Peter Spégel ◽  
Siri Malmgren ◽  
Vladimir V. Sharoyko ◽  
Philip Newsholme ◽  
Thomas Koeck ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Lines ◽  
Target Genes ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Gas Chromatography Mass Spectrometry ◽  
Glycolytic Metabolism ◽  
Β Cell ◽  
Acid Cycle ◽  
Stimulus Secretion Coupling

Insulin secretion from pancreatic β-cells is controlled by complex metabolic and energetic changes provoked by exposure to metabolic fuels. Perturbations in these processes lead to impaired insulin secretion, the ultimate cause of T2D (Type 2 diabetes). To increase our understanding of stimulus–secretion coupling and metabolic processes potentially involved in the pathogenesis of T2D, a comprehensive investigation of the metabolic response in the glucose-responsive INS-1 832/13 and glucose-unresponsive INS-1 832/2 β-cell lines was performed. For this metabolomics analysis, we used GC/MS (gas chromatography/mass spectrometry) combined with multivariate statistics. We found that perturbed secretion in the 832/2 line was characterized by disturbed coupling of glycolytic and TCA (tricarboxylic acid)-cycle metabolism. The importance of this metabolic coupling was reinforced by our observation that insulin secretion partially could be reinstated by stimulation of the cells with mitochondrial fuels which bypass glycolytic metabolism. Furthermore, metabolic and functional profiling of additional β-cell lines (INS-1, INS-1 832/1) confirmed the important role of coupled glycolytic and TCA-cycle metabolism in stimulus–secretion coupling. Dependence of the unresponsive clones on glycolytic metabolism was paralleled by increased stabilization of HIF-1α (hypoxia-inducible factor 1α). The relevance of a similar perturbation for human T2D was suggested by increased expression of HIF-1α target genes in islets from T2D patients.

scholarly journals β-Cell Differentiation from a Human Pancreatic Cell Line in Vitro and in Vivo

2001 ◽  
Vol 15 (3) ◽  
pp. 476-483 ◽  
Author(s):  
Dominique Dufayet de la Tour ◽  
Tanya Halvorsen ◽  
Carla Demeterco ◽  
Björn Tyrberg ◽  
Pamela Itkin-Ansari ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Differentiation ◽  
Cell Transplantation ◽  
Cell Lines ◽  
Β Cells ◽  
Β Cell ◽  
Cell Transplantation Therapy ◽  
Transplantation Therapy

Abstract Cell transplantation therapy for diabetes is limited by an inadequate supply of cells exhibiting glucose-responsive insulin secretion. To generate an unlimited supply of human β-cells, inducibly transformed pancreatic β-cell lines have been created by expression of dominant oncogenes. The cell lines grow indefinitely but lose differentiated function. Induction of β-cell differentiation was achieved by stimulating the signaling pathways downstream of the transcription factor PDX-1, cell-cell contact, and the glucagon-like peptide (GLP-1) receptor. Synergistic activation of those pathways resulted in differentiation into functional β-cells exhibiting glucose-responsive insulin secretion in vitro. Both oncogene-expressing and oncogene-deleted cells were transplanted into nude mice and found to exhibit glucose-responsive insulin secretion in vivo. The ability to grow unlimited quantities of human β-cells is a major step toward developing a cell transplantation therapy for diabetes.

Extracellular acidification parallels insulin secretion in INS-1 and HIT-T15 β-cell lines

2002 ◽  
Vol 293 (4) ◽  
pp. 1168-1173 ◽  
Author(s):  
Douglas B Luckie ◽  
John H Wilterding ◽  
Joseph J Maleszewski ◽  
Errett C Hobbs ◽  
L Karl Olson
Keyword(s):  
Insulin Secretion ◽  
Cell Lines ◽  
Β Cell ◽  
Extracellular Acidification

scholarly journals GRK2 regulates GLP-1R-mediated early phase insulin secretion in vivo

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Alba C. Arcones ◽  
Rocío Vila-Bedmar ◽  
Mercedes Mirasierra ◽  
Marta Cruces-Sande ◽  
Mario Vallejo ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
G Protein ◽  
Insulin Release ◽  
Cell Lines ◽  
Early Phase ◽  
G Protein Coupled Receptor ◽  
Β Cell ◽  
Insulin Secretion In Vivo ◽  
G Protein Coupled

Abstract Background Insulin secretion from the pancreatic β-cell is finely modulated by different signals to allow an adequate control of glucose homeostasis. Incretin hormones such as glucagon-like peptide-1 (GLP-1) act as key physiological potentiators of insulin release through binding to the G protein-coupled receptor GLP-1R. Another key regulator of insulin signaling is the Ser/Thr kinase G protein-coupled receptor kinase 2 (GRK2). However, whether GRK2 affects insulin secretion or if GRK2 can control incretin actions in vivo remains to be analyzed. Results Using GRK2 hemizygous mice, isolated pancreatic islets, and model β-cell lines, we have uncovered a relevant physiological role for GRK2 as a regulator of incretin-mediated insulin secretion in vivo. Feeding, oral glucose gavage, or administration of GLP-1R agonists in animals with reduced GRK2 levels (GRK2+/− mice) resulted in enhanced early phase insulin release without affecting late phase secretion. In contrast, intraperitoneal glucose-induced insulin release was not affected. This effect was recapitulated in isolated islets and correlated with the increased size or priming efficacy of the readily releasable pool (RRP) of insulin granules that was observed in GRK2+/− mice. Using nanoBRET in β-cell lines, we found that stimulation of GLP-1R promoted GRK2 association to this receptor and that GRK2 protein and kinase activity were required for subsequent β-arrestin recruitment. Conclusions Overall, our data suggest that GRK2 is an important negative modulator of GLP-1R-mediated insulin secretion and that GRK2-interfering strategies may favor β-cell insulin secretion specifically during the early phase, an effect that may carry interesting therapeutic applications.

Cellular Interaction Between Mouse Pancreatic α-Cell and β-Cell Lines: Possible Contact-Dependent Inhibition of Insulin Secretion

2003 ◽  
Vol 228 (10) ◽  
pp. 1227-1233 ◽  
Author(s):  
Kazuyuki Hamaguchi ◽  
Naoko Utsunomiya ◽  
Ryosaburo Takaki ◽  
Hironobu Yoshimatsu ◽  
Toshiie Sakata
Keyword(s):  
Insulin Secretion ◽  
Cell Lines ◽  
Cellular Interaction ◽  
Β Cell ◽  
Dependent Inhibition

scholarly journals AMP-activated protein kinase is activated by low glucose in cell lines derived from pancreatic β cells, and may regulate insulin release

1998 ◽  
Vol 335 (3) ◽  
pp. 533-539 ◽  
Author(s):  
Ian P. SALT ◽  
Gabriele JOHNSON ◽  
Stephen J. H. ASHCROFT ◽  
D. Grahame HARDIE
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Insulin Release ◽  
Cell Lines ◽  
Cell Types ◽  
Β Cell ◽  
Upstream Kinase ◽  
Ampk Activity ◽  
Two Parameters ◽  
Amp Activated Protein Kinase

The role of the AMP-activated protein kinase (AMPK) cascade in the glucose-sensitive pancreatic β cell lines HIT-T15 and INS-1 was addressed. In both cell types, removal of glucose leads to a > 5-fold activation of AMPK activity. Activation of AMPK was due to phosphorylation, since the effect was reversed by protein phosphatase treatment of the extracts, and was restored by re-addition of MgATP and the purified upstream kinase. When the effects of different concentrations of medium glucose were examined, insulin secretion and AMPK activity were inversely related, and varied over the same concentration range. The activation in response to glucose removal appeared to be due to changes in the concentration of the known regulators of the cascade, i.e. AMP and ATP, since AMPK activation was associated with a large increase in the cellular AMP/ATP ratio, and the two parameters varied over the same range of glucose concentrations. In late-passage HIT-T15 cells that had lost the glucose-dependent insulin secretion response, both AMPK activity and the AMP/ATP ratio also became insensitive to the extracellular glucose concentration. Treatment of INS-1 cells, but not HIT-T15 cells, with AICA riboside (5-aminoimidazole-4-carboxamide riboside) results in accumulation of the ribotide, ZMP (AICA riboside monophosphate), and activation of AMPK. AICA riboside treatment of INS-1 cells, and of isolated rat islets, had both inhibitory and stimulatory effects on insulin secretion. These results show that in β cell lines the AMP-activated protein kinase, like its yeast homologue the SNF1 complex, can respond to the level of glucose in the medium, and may be involved in regulating insulin release.

Regulation of Insulin Secretion from β-Cell Lines Derived from Transgenic Mice Insulinomas Resembles that of Normal β-Cells*

Endocrinology ◽  
1990 ◽  
Vol 126 (6) ◽  
pp. 2815-2822 ◽  
Author(s):  
RUSSELL D’AMBRA ◽  
MANJU SURANA ◽  
SHIMON EFRAT ◽  
ROBERT G. STARR ◽  
NORMAN FLEISCHER
Keyword(s):  
Insulin Secretion ◽  
Transgenic Mice ◽  
Cell Lines ◽  
Β Cells ◽  
Β Cell

The Effect of Dietary Fat on Insulin Secretion and Pancreatic β-Cell Mass in 90% Pancreatectomized Diabetic Rats

2007 ◽  
Vol 36 (2) ◽  
pp. 186-193 ◽  
Author(s):  
Sun-Min Park ◽  
Chun-Hee Park ◽  
Sang-Mee Hong
Keyword(s):  
Insulin Secretion ◽  
Dietary Fat ◽  
Cell Mass ◽  
Diabetic Rats ◽  
Pancreatic Β Cell ◽  
Β Cell
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