scholarly journals Cloning and expression of rat pancreatic β-cell malonyl-CoA decarboxylase

1999 ◽  
Vol 340 (1) ◽  
pp. 213-217 ◽  
Author(s):  
Nicolas VOILLEY ◽  
Raphaël RODUIT ◽  
Raffaela VICARETTI ◽  
Christophe BONNY ◽  
Gérard WAEBER ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cloning And Expression ◽  
Rat Tissues ◽  
Distribution Analysis ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Methionine Residue ◽  
Malonyl Coa ◽  
Mrna Tissue Distribution ◽  
Wide Range

To gain insight into the function and regulation of malonyl-CoA decarboxylase (MCD) we have cloned rat MCD cDNA from a differentiated insulin-secreting pancreatic β-cell-line cDNA library. The full-length cDNA sequence shows 69% identity with the cDNA cloned previously from the goose uropygial gland, and predicts a 492 amino acid protein of 54.7 kDa. The open reading frame contains an N-terminal mitochondrial targeting sequence and the C-terminal part of the enzyme ends with a peroxisomal (Ser-Lys-Leu) targeting motif. Since the sequence does not reveal hydrophobic domains, MCD is most likely expressed in the mitochondrial matrix and inside the peroxisomes. A second methionine residue, located 3ʹ of the mitochondrial presequence, might be the first amino acid of a putative cytosolic MCD, since the nucleotide sequence around it fits fairly well with a consensus Kozak site for translation initiation. However, primer extension detects the presence of only one transcript initiating upstream of the first ATG, indicating that the major, if not exclusive, transcript expressed in the pancreatic β-cell encodes MCD with its mitochondrial presequence. The sequence also shows multiple possible sites of phosphorylation by casein kinase II and protein kinase C. mRNA tissue-distribution analysis indicates a transcript of 2.2 kb, and that the MCD gene is expressed over a wide range of rat tissues. The distribution of the enzyme shows a broad range of activities from very low in the brain to elevated in the liver and heart. The results provide the foundations for further studies of the role of MCD in lipid metabolism and metabolic signalling in various tissues.

scholarly journals Cloning and expression of rat pancreatic β-cell malonyl-CoA decarboxylase

1999 ◽  
Vol 340 (1) ◽  
pp. 213 ◽  
Author(s):  
Nicolas VOILLEY ◽  
Raphaël RODUIT ◽  
Raffaela VICARETTI ◽  
Christophe BONNY ◽  
Gérard WAEBER ◽  
...  
Keyword(s):  
Cloning And Expression ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Malonyl Coa

Volume-sensitive amino acid efflux from a pancreatic β-cell line

2000 ◽  
Vol 162 (1-2) ◽  
pp. 201-208 ◽  
Author(s):  
A.C.G. Grant ◽  
J. Thomson ◽  
V.A. Zammit ◽  
D.B. Shennan
Keyword(s):  
Amino Acid ◽  
Cell Line ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Amino Acid Efflux

scholarly journals Molecular cloning and expression of a rat hepatic multiple inositol polyphosphate phosphatase

1997 ◽  
Vol 328 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Andrew CRAXTON ◽  
J. James CAFFREY ◽  
William BURKHART ◽  
T. Stephen SAFRANY ◽  
B. Stephen SHEARS
Keyword(s):  
Endoplasmic Reticulum ◽  
Amino Acid ◽  
Catalytic Domain ◽  
Cloning And Expression ◽  
Predicted Amino Acid Sequence ◽  
Rat Tissues ◽  
Inositol Polyphosphate ◽  
Inositol Hexakisphosphate ◽  
Diverse Range ◽  
Amino Acid Region

The characterization of the multiple inositol polyphosphate phosphatase (MIPP) is fundamental to our understanding of how cells control the signalling activities of ‘higher’ inositol polyphosphates. We now describe our isolation of a 2.3 kb cDNA clone of a rat hepatic form of MIPP. The predicted amino acid sequence of MIPP includes an 18 amino acid region that aligned with approximately 60% identity with the catalytic domain of a fungal inositol hexakisphosphate phosphatase (phytase A); the similarity encompassed conservation of the RHGXRXP signature of the histidine acid phosphatase family. A histidine-tagged, truncated form of MIPP was expressed in Escherichia coli and the enzymic specificity of the recombinant protein was characterized: Ins(1,3,4,5,6)P5 was hydrolysed, first to Ins(1,4,5,6)P4 and then to Ins(1,4,5)P3, by consecutive 3- and 6-phosphatase activities. Inositol hexakisphosphate was catabolized without specificity towards a particular phosphate group, but in contrast, MIPP only removed the β-phosphate from the 5-diphosphate group of diphosphoinositol pentakisphosphate. These data, which are consistent with the substrate specificities of native (but not homogeneous) MIPP isolated from rat liver, provide the first demonstration that a single enzyme is responsible for this diverse range of specific catalytic activities. A 2.5 kb transcript of MIPP mRNA was present in all rat tissues that were examined, but was most highly expressed in kidney and liver. The predicted C-terminus of MIPP is comprised of the tetrapeptide SDEL, which is considered a signal for retaining soluble proteins in the lumen of the endoplasmic reticulum; the presence of this sequence provides a molecular explanation for our earlier biochemical demonstration that the endoplasmic reticulum contains substantial MIPP activity [Ali, Craxton and Shears (1993) J. Biol. Chem. 268, 6161-6167].

scholarly journals Amino acid taste receptor regulates insulin secretion in pancreatic β-cell line MIN6 cells

2011 ◽  
Vol 16 (5) ◽  
pp. 608-616 ◽  
Author(s):  
Manami Oya ◽  
Hideyuki Suzuki ◽  
Yuichiro Watanabe ◽  
Moritoshi Sato ◽  
Takashi Tsuboi
Keyword(s):  
Insulin Secretion ◽  
Amino Acid ◽  
Cell Line ◽  
Taste Receptor ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Min6 Cells

Regulation of pancreatic β-cell electrical activity and insulin release by physiological amino acid concentrations

1997 ◽  
Vol 433 (6) ◽  
pp. 699-704 ◽  
Author(s):  
Sonia Bolea ◽  
Jose A. G. Pertusa ◽  
Franz Martín ◽  
Juan V. Sanchez-Andrés ◽  
B. Soria
Keyword(s):  
Amino Acid ◽  
Electrical Activity ◽  
Insulin Release ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Amino Acid Concentrations

Plasma amino acid values and pancreatic β-cell function in phenylketonuria

1987 ◽  
Vol 10 (1) ◽  
pp. 66-72 ◽  
Author(s):  
I. Antonozzi ◽  
C. Carducci ◽  
L. Vestri ◽  
V. Manzari ◽  
R. Dominici
Keyword(s):  
Amino Acid ◽  
Cell Function ◽  
Plasma Amino Acid ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Β Cell Function

scholarly journals Regulation of pancreatic β-cell mitochondrial metabolism: influence of Ca2+, substrate and ADP

1996 ◽  
Vol 318 (2) ◽  
pp. 615-621 ◽  
Author(s):  
Vildan N CIVELEK ◽  
Jude T DEENEY ◽  
Nicholas J SHALOSKY ◽  
Keith TORNHEIM ◽  
Richard G. HANSFORD ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Pyruvate Dehydrogenase ◽  
Redox State ◽  
Co2 Production ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Mitochondrial Redox State ◽  
Malonyl Coa

To gain insight into the regulation of pancreatic β-cell mitochondrial metabolism, the direct effects on respiration of different mitochondrial substrates, variations in the ATP/ADP ratio and free Ca2+ were examined using isolated mitochondria and permeabilized clonal pancreatic β-cells (HIT). Respiration from pyruvate was high and not influenced by Ca2+ in State 3 or under various redox states and fixed values of the ATP/ADP ratio; nevertheless, high Ca2+ elevated pyridine nucleotide fluorescence, indicating activation of pyruvate dehydrogenase by Ca2+. Furthermore, in the presence of pyruvate, elevated Ca2+ stimulated CO2 production from pyruvate, increased citrate production and efflux from the mitochondria and inhibited CO2 production from palmitate. The latter observation suggests that β-cell fatty acid oxidation is not regulated exclusively by malonyl-CoA but also by the mitochondrial redox state. α-Glycerophosphate (α-GP) oxidation was Ca2+-dependent with a half-maximal rate observed at around 300 nM Ca2+. We have recently demonstrated that increases in respiration precede increases in Ca2+ in glucose-stimulated clonal pancreatic β-cells (HIT), indicating that Ca2+ is not responsible for the initial stimulation of respiration [Civelek, Deeney, Kubik, Schultz, Tornheim and Corkey (1996) Biochem. J. 315, 1015–1019]. It is suggested that respiration is stimulated by increased substrate (α-GP and pyruvate) supply together with oscillatory increases in ADP [Nilsson, Schultz, Berggren, Corkey and Tornheim (1996) Biochem. J. 314, 91–94]. The rise in Ca2+, which in itself may not significantly increase net respiration, could have the important functions of (1) activating the α-GP shuttle, to maintain an oxidized cytosol and high glycolytic flux; (2) activating pyruvate dehydrogenase, and indirectly pyruvate carboxylase, to sustain production of citrate and hence the putative signal coupling factors, malonyl-CoA and acyl-CoA; and (3) increasing mitochondrial redox state to implement the switch from fatty acid to pyruvate oxidation.

scholarly journals GCN2 regulates pancreatic β cell mass by sensing intracellular amino acid levels

JCI Insight ◽  
2020 ◽  
Vol 5 (9) ◽  
Author(s):  
Ayumi Kanno ◽  
Shun-ichiro Asahara ◽  
Ayuko Furubayashi ◽  
Katsuhisa Masuda ◽  
Risa Yoshitomi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Mass ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Intracellular Amino Acid ◽  
Amino Acid Levels

Adipokines as key players in β cell function and failure

2019 ◽  
Vol 133 (22) ◽  
pp. 2317-2327 ◽  
Author(s):  
Nicolás Gómez-Banoy ◽  
James C. Lo
Keyword(s):  
Metabolic Diseases ◽  
Cell Function ◽  
Whole Body ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Axis ◽  
Β Cell Function ◽  
Prevalence Of Obesity ◽  
Specific Factors ◽  
Whole Body Metabolism

Abstract The growing prevalence of obesity and its related metabolic diseases, mainly Type 2 diabetes (T2D), has increased the interest in adipose tissue (AT) and its role as a principal metabolic orchestrator. Two decades of research have now shown that ATs act as an endocrine organ, secreting soluble factors termed adipocytokines or adipokines. These adipokines play crucial roles in whole-body metabolism with different mechanisms of action largely dependent on the tissue or cell type they are acting on. The pancreatic β cell, a key regulator of glucose metabolism due to its ability to produce and secrete insulin, has been identified as a target for several adipokines. This review will focus on how adipokines affect pancreatic β cell function and their impact on pancreatic β cell survival in disease contexts such as diabetes. Initially, the “classic” adipokines will be discussed, followed by novel secreted adipocyte-specific factors that show therapeutic promise in regulating the adipose–pancreatic β cell axis.

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