Differential regulation of [Ca2+]i oscillations in mouse pancreatic islets by glucose, α-ketoisocaproic acid, glyceraldehyde and glycolytic intermediates

Lenzen, Sigurd; Lerch, Magnus; Peckmann, Thomas; Tiedge, Markus

doi:10.1016/s0304-4165(00)00100-8

Cited by 33 publications

(24 citation statements)

References 33 publications

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“…In some studies, KIC, MeP, glyceraldehyde, and dihydroxyacetone were reported to be unable to elicit Ca 2ϩ oscillations alone (17) or with glucose present (5,21). In other reports, KIC induced slow Ca 2ϩ oscillations (31) and secretion in the absence of substimulatory glucose (14,40), which agrees with our data.…”

Section: Discussionsupporting

confidence: 92%

Rhythm of the β-cell oscillator is not governed by a single regulator: multiple systems contribute to oscillatory behavior

Heart¹,

Smith²

2007

American Journal of Physiology-Endocrinology and Metabolism

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Section: Discussionsupporting

confidence: 92%

Rhythm of the β-cell oscillator is not governed by a single regulator: multiple systems contribute to oscillatory behavior

Heart¹,

Smith²

2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Firstly, a channeling of the first steps of glycolysis through glucokinase could explain the phenomenon that glucose metabolism in beta cells is dependent upon glucokinase activity even though the high affinity hexokinase isoenzyme comprises 50 -70% of total glucose phosphorylation activity in pancreatic islets (1,58,59). Secondly, the effector molecule fructose 2,6-bisphosphate may participate in metabolic oscillations in beta cells through an allosteric activation of phosphofructokinase that may form a regulatory cycle through a complex of glycolytic enzymes with the PFK-2/FBPase-2 (60,61). This is of particular interest because enzyme tunneling of hexose 6-phosphates has been already demonstrated in pancreatic islets from rats (62).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Glucokinase-binding Protein Epitopes by a Phage-displayed Peptide Library

Baltrusch¹,

Lenzen²,

Okar³

et al. 2001

Journal of Biological Chemistry

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The low affinity glucose-phosphorylating enzyme glucokinase shows the phenomenon of intracellular translocation in beta cells of the pancreas and the liver. To identify potential binding partners of glucokinase by a systematic strategy, human beta cell glucokinase was screened by a 12-mer random peptide library displayed by the M13 phage. This panning procedure revealed two consensus motifs with a high binding affinity for glucokinase. The first consensus motif, LSAXXVAG, corresponded to the glucokinase regulatory protein of the liver. The second consensus motif, SLKVWT, showed a complete homology to the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), which acts as a key regulator of glucose metabolism. Through yeast twohybrid analysis it became evident that the binding of glucokinase to PFK-2/FBPase-2 is conferred by the bisphosphatase domain, whereas the kinase domain is responsible for dimerization. 5-Rapid amplification of cDNA ends analysis and Northern blot analysis revealed that rat pancreatic islets express the brain isoform of PFK-2/FBPase-2. A minor portion of the islet PFK-2/FBPase-2 cDNA clones comprised a novel splice variant with 8 additional amino acids in the kinase domain. The binding of the islet/brain PFK-2/ FBPase-2 isoform to glucokinase was comparable with that of the liver isoform. The interaction between glucokinase and PFK-2/FBPase-2 may provide the rationale for recent observations of a fructose-2,6-bisphosphate level-dependent partial channeling of glycolytic intermediates between glucokinase and glycolytic enzymes. In pancreatic beta cells this interaction may have a regulatory function for the metabolic stimulussecretion coupling. Changes in fructose-2,6-bisphosphate levels and modulation of PFK-2/FBPase-2 activities may participate in the physiological regulation of glucokinase-mediated glucose-induced insulin secretion.The low affinity glucose-phosphorylating enzyme glucokinase (hexokinase type IV) plays a pivotal role for the coupling of physiological millimolar glucose concentration changes to glycolysis in liver, pancreatic beta cells, and neuroendocrine cells (1-7). In pancreatic beta cells glucokinase, acting as a glucose sensor, catalyzes the rate-limiting step for glucosestimulated insulin secretion (1, 2, 4, 8). Studies in glucokinase knock-out mice, as well as the metabolic profile of diabetic patients with mutations of the glucokinase gene, provide evidence that the glucose sensor function of this enzyme in pancreatic beta cells can be fulfilled only within a narrow range of enzyme activity (5, 9 -12). Thus principles of posttranslational regulation of beta cell glucokinase have gained special interest in recent years (13-18). Liver glucokinase is regulated by insulin and glucagon on the transcriptional and translational level and by the glucokinase regulatory protein (GRP) 1 via translocation between cytosol and nucleus (6, 19 -23). In particular this translocation confers a short term adaptation of glucose metabolism to chang...

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“…PFK1 is the established mediator of slow glycolytic oscillations (67). This is why only glucose, which generates a glucokinase-mediated metabolic flux through glycolysis, induces slow oscillations of [Ca 2ϩ ] i ; this is in contrast to insulin secretory substrates that enter glycolysis below PFK1 (67,68). PFK2, the generator of Fru-2,6-P 2 , modulates the frequency of and modifies the threshold for glycolytic oscillations by lowering the PFK1 threshold and increasing the activity of PFK1, thereby generating metabolic oscillations as documented by oscillations of [Ca 2ϩ ] i as a surrogate of pulsatile insulin release.…”

Section: A Fresh View Of Glycolysis: the Importance Of The Fructose Ementioning

confidence: 99%

A Fresh View of Glycolysis and Glucokinase Regulation: History and Current Status

Lenzen

2014

Journal of Biological Chemistry

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126

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This minireview looks back at a century of glycolysis research with a focus on the mechanisms of flux regulation. Traditionally, glycolysis is regarded as a feeder pathway that prepares glucose for further catabolism and energy production. However, glycolysis is much more than that, in particular in those tissues that express the low affinity glucose-phosphorylating enzyme glucokinase. This enzyme equips the glycolytic pathway with a special steering function for the regulation of intermediary metabolism. In beta cells, glycolysis acts as a transducer for triggering and amplifying physiological glucose-induced insulin secretion. On the basis of these considerations, I have defined a glycolytic flux regulatory unit composed of the two fructose ester steps of this pathway with various enzymes and metabolites that regulate glycolysis.

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Differential regulation of [Ca2+]i oscillations in mouse pancreatic islets by glucose, α-ketoisocaproic acid, glyceraldehyde and glycolytic intermediates

Cited by 33 publications

References 33 publications

Rhythm of the β-cell oscillator is not governed by a single regulator: multiple systems contribute to oscillatory behavior

Rhythm of the β-cell oscillator is not governed by a single regulator: multiple systems contribute to oscillatory behavior

Characterization of Glucokinase-binding Protein Epitopes by a Phage-displayed Peptide Library

A Fresh View of Glycolysis and Glucokinase Regulation: History and Current Status

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