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

scholarly journals Molecular mechanisms responsible for the sexual dimorphism in pancreatic β-cell insulin release

2021 ◽  
Vol 154 (9) ◽  
Author(s):  
Noelia Jacobo-Piqueras ◽  
Tamara Theiner ◽  
Stefanie M. Geisler ◽  
Petronel Tuluc
Keyword(s):  
Sexual Dimorphism ◽  
Electrical Activity ◽  
Insulin Release ◽  
Molecular Mechanisms ◽  
Resting Membrane Potential ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Specific Expression ◽  
Extracellular Glucose Concentration

In humans, type 2 diabetes mellitus (T2DM) has a higher incidence in males compared to females, a phenotype recapitulated by many rodent models. While the sex difference in insulin sensitivity partially accounts for this phenomenon, hitherto uncharacterized differences in pancreatic β-cell insulin release strongly contribute. Here, we show that stepwise increase in extracellular glucose concentration (2, 5, 7.5, 10, 15, 20 mM) induced electrical activity in β cells of both sexes with similar glucose sensitivity (female, EC50 = 9.45 ± 0.15 mM; male, EC50 = 9.42 ± 0.16 mM). However, female β cells’ resting membrane potential (RMP) and inter-spike potential (IP) were significantly higher compared to males (e.g., at 15 mM glucose: male RMP = −82.7 ± 6.3, IP = −74.3 ± 6.8 mV; female RMP = −50.0 ± 7.1, IP = −41.2 ± 7.3 mV). Females also showed higher frequency of trains of action potential (AP; at 10 mM glucose: male F = 1.13 ± 0.15 trains/min; female F = 1.78 ± 0.25 trains/min) and longer AP-burst duration (e.g., at 10 mM glucose: male, 241 ± 30.8 ms; female, 419 ± 60.2 ms). The higher RMP in females reduced the voltage-gated calcium channel (CaV) availability by ∼60%. This explains the paradoxical observation that, despite identical CaV expression levels and higher electrical activity, the islet Ca2+ transients were smaller in females compared to males. Interestingly, the different RMPs are not caused by altered KATP, TASK, or TALK K+ currents. However, stromatoxin-1–sensitive KV2.1 K+ current amplitude was almost double in males (IK = 130.93 ± 7.05 pA/pF) compared to females (IK = 75.85 ± 11.3 pA/pF) when measured at +80 mV. Our results are in agreement with previous findings showing that KV2.1 genetic deletion or pharmacological block leads to higher insulin release and β-cell survival. Therefore, we propose the sex-specific expression of KV2.1 to be the mechanism underlying the observed sexual dimorphism in insulin release and the incidence of T2DM.

The agouti gene product stimulates pancreatic β-cell Ca2+ signaling and insulin release

1999 ◽  
Vol 1 (1) ◽  
pp. 11-19 ◽  
Author(s):  
B. Z. XUE ◽  
W. O. WILKISON ◽  
R. L. MYNATT ◽  
N. MOUSTAID ◽  
M. GOLDMAN ◽  
...  
Keyword(s):  
Gene Product ◽  
Insulin Release ◽  
Fold Increase ◽  
Cell Types ◽  
Human Pancreas ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Agouti Protein ◽  
Intracellular Ca ◽  
Agouti Gene

Xue, B. Z., W. O. Wilkison, R. L. Mynatt, N. Moustaid, M. Goldman, and M. B. Zemel. The agouti gene product stimulates pancreatic β-cell Ca2+ signaling and insulin release. Physiol. Genomics 1: 11-19, 1999.—Ubiquitous expression of the mouse agouti gene results in obesity and hyperinsulinemia. Human agouti is expressed in adipose tissue, and we found recombinant agouti protein to stimulate lipogenesis in adipocytes in a Ca2+-dependent fashion. However, adipocyte-specific agouti transgenic mice only became obese in the presence of hyperinsulinemia. Because intracellular Ca2+ concentration ([Ca2+]i) is a primary signal for insulin release, and we have shown agouti protein to increase [Ca2+]i in several cell types, we examined the effects of agouti on [Ca2+]i and insulin release. We demonstrated the expression of agouti in human pancreas and generated recombinant agouti to study its effects on Ca2+ signaling and insulin release. Agouti (100 nM) stimulated Ca2+ influx, [Ca2+]i increase, and a marked stimulation of insulin release in two β-cell lines (RIN-5F and HIT-T15; P < 0.05). Agouti exerted comparable effects in isolated human pancreatic islets and β-cells, with a 5-fold increase in Ca2+ influx ( P < 0.001) and a 2.2-fold increase in insulin release ( P < 0.01). These data suggest a potential role for agouti in the development of hyperinsulinemia in humans.

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

Life and death decisions of the pancreatic β-cell: the role of fatty acids

2006 ◽  
Vol 112 (1) ◽  
pp. 27-42 ◽  
Author(s):  
Philip Newsholme ◽  
Deirdre Keane ◽  
Hannah J. Welters ◽  
Noel G. Morgan
Keyword(s):  
Fatty Acids ◽  
Insulin Release ◽  
Chronic Exposure ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Endogenous Fatty Acid ◽  
Gene And Protein Expression ◽  
Β Cell Function

Both stimulatory and detrimental effects of NEFAs (non-esterified fatty acids) on pancreatic β-cells have been recognized. Acute exposure of the pancreatic β-cell to high glucose concentrations and/or saturated NEFAs results in a substantial increase in insulin release, whereas chronic exposure results in desensitization and suppression of secretion, followed by induction of apoptosis. Some unsaturated NEFAs also promote insulin release acutely, but they are less toxic to β-cells during chronic exposure and can even exert positive protective effects. Therefore changes in the levels of NEFAs are likely to be important for the regulation of β-cell function and viability under physiological conditions. In addition, the switching between endogenous fatty acid synthesis or oxidation in the β-cell, together with alterations in neutral lipid accumulation, may have critical implications for β-cell function and integrity. Long-chain acyl-CoA (formed from either endogenously synthesized or exogenous fatty acids) controls several aspects of β-cell function, including activation of specific isoenzymes of PKC (protein kinase C), modulation of ion channels, protein acylation, ceramide formation and/or NO-mediated apoptosis, and transcription factor activity. In this review, we describe the effects of exogenous and endogenous fatty acids on β-cell metabolism and gene and protein expression, and have explored the outcomes with respect to insulin secretion and β-cell integrity.

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.

Role of mitochondria in metabolism-secretion coupling of insulin release in the pancreatic β-cell

BioFactors ◽  
1998 ◽  
Vol 8 (3-4) ◽  
pp. 255-262 ◽  
Author(s):  
Pierre Maechler ◽  
Claes B. Wollheim
Keyword(s):  
Insulin Release ◽  
Pancreatic Β Cell ◽  
Β Cell

CHANGES OF FREE AMINO ACIDS IN PANCREATIC β-CELLS AFTER STARVATION AND SUBSTRATE DEPRIVATION

1974 ◽  
Vol 75 (1) ◽  
pp. 105-118 ◽  
Author(s):  
Erik Gylfe
Keyword(s):  
Amino Acid ◽  
Aspartic Acid ◽  
Free Amino ◽  
Aminobutyric Acid ◽  
Β Cell ◽  
Freeze Dried ◽  
Amino Acid Efflux ◽  
Substrate Deprivation ◽  
Amino Acid Concentrations ◽  
Very High

ABSTRACT A procedure for free amino acid measurements in β-cell-rich pancreatic islets from obese-hyperglycaemic mice involving reaction with 3H-dansyl chloride and subsequent chromatographic separation was studied. A characteristic feature of the islets was the presence of γ-aminobutyric acid and of very high taurine concentrations. Islets dissected from fresh pancreas contained more leucine and valine than specimens obtained from freeze-dried pancreatic sections. When micro-dissected islets were incubated in substrate-free medium the concentrations of leucine and valine remained high, whereas aspartic acid decreased. Perifusion of islets with the same type of medium, however, depressed the concentrations of glycine, leucine, lysine, phenylalanine and valine. Starvation increased the β-cell concentrations of γ-aminobutyric acid and leucine and reduced those of aspartic acid and glutamic acid. The possibilities that the amino acid concentrations are influenced by amino acid efflux or the uptake of secreted insulin in combination with protein catabolism are discussed.

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