scholarly journals Regulation of glucokinase and GLUT-2 glucose-transporter gene expression in pancreatic B-cells

1991 ◽  
Vol 279 (3) ◽  
pp. 899-901 ◽  
Author(s):  
M Tiedge ◽  
S Lenzen
Keyword(s):  
Insulin Secretion ◽  
B Cells ◽  
B Cell ◽  
Glucose Transporter ◽  
Transcriptional Level ◽  
Signal Recognition ◽  
Transporter Gene ◽  
Physiological Regulation ◽  
Mrna Species ◽  
Pancreatic B Cells

Glucokinase (EC 2.7.1.2) is the signal-recognition enzyme in pancreatic B-cells for initiation of glucose-induced insulin secretion. We show here that both the glucokinase and glucose-transporter GLUT-2 genes are regulated physiologically. Fasting decreased B-cell glucokinase and glucose-transporter GLUT-2 mRNA in pancreatic B-cells as well as in liver, whereas refeeding induced expression of both genes. In pancreatic B-cells a approximately 4.4 kb glucokinase-related mRNA was detectable, in addition to the 2.8 kb form. This approximately 4.4 kb glucokinase transcript was drastically decreased during refeeding. The 2.8 kb mRNA, which is typical for pancreatic B-cells, was accompanied after refeeding by a 2.4 kb mRNA species typical for liver glucokinase. Starvation primarily decreased the 2.8 kb pancreatic B-cell glucokinase mRNA species. The concordant regulation of both genes may represent the basis for the physiological regulation of glucose-induced insulin secretion at a transcriptional level.

Glucokinase in pancreatic B-cells and its inhibition by alloxan

1987 ◽  
Vol 115 (1) ◽  
pp. 21-29 ◽  
Author(s):  
Sigurd Lenzen ◽  
Markus Tiedge ◽  
Uwe Panten
Keyword(s):  
Insulin Secretion ◽  
B Cells ◽  
B Cell ◽  
Metabolic Flux ◽  
Inhibitory Concentration ◽  
Pancreatic B Cell ◽  
High K ◽  
Pancreatic B Cells ◽  
Low K

Abstract. Characterization of glucokinase in pancreatic B-cells from ob/ob mice and from rat liver revealed identical characteristics. A narrow substrate specificity; high Km values for the two substrates, D-glucose and D-mannose, in the range of 10 and 20 mmol/l, respectively; higher Vmax values for D-glucose than for D-mannose; inhibition of glucokinase activities by D-mannoheptulose and by a specific glucokinase antibody. These characteristics distinguish glucokinase in soluble cytoplasmic fractions of pancreatic B-cells and liver from low Km hexokinases. Alloxan is a pancreatic B-cell cytotoxic agent, which has been widely used as a tool for the elucidation of the mechanisms of insulin secretion, because its inhibitory action on insulin secretion has been presumed to be intimately related to the mechanism of glucose-induced insulin secretion. Alloxan inhibited glucokinase but not hexokinase activity in cytoplasmic fractions of pancreatic B-cells and liver. The half maximal inhibitory concentration of alloxan was 5 μmol/l. Glucokinase activity was protected from alloxan toxicity only by D-glucose and D-mannose; the α anomer of D-glucose provided significantly greater protection than the β anomer. The non-metabolizable sugar 3-0-methyl-D-glucose did not provide protection of glucokinase activity against inhibition by alloxan. Thus, inhibition of pancreatic B-cell glucokinase may contribute to the inhibition of glucose-induced insulin secretion by alloxan. These results support the contention that glucokinase regulates the metabolic flux rate through the glycolytic chain in the pancreatic B-cell and thereby generates the signal for glucose-induced insulin secretion.

Recovery of glucose-induced insulin secretion in a rat model of NIDDM is not accompanied by return of the B-cell GLUT2 glucose transporter

Diabetes ◽  
1992 ◽  
Vol 41 (10) ◽  
pp. 1320-1327 ◽  
Author(s):  
C. Chen ◽  
B. Thorens ◽  
S. Bonner-Weir ◽  
G. C. Weir ◽  
J. L. Leahy
Keyword(s):  
Insulin Secretion ◽  
B Cell ◽  
Rat Model ◽  
Glucose Transporter ◽  
Glut2 Glucose Transporter

BCL2 protein expression parallels its mRNA level in normal and malignant B cells

Blood ◽  
2004 ◽  
Vol 104 (9) ◽  
pp. 2936-2939 ◽  
Author(s):  
Yulei Shen ◽  
Javeed Iqbal ◽  
James Z. Huang ◽  
Guimei Zhou ◽  
Wing C. Chan
Keyword(s):  
B Cells ◽  
Protein Expression ◽  
B Cell ◽  
Posttranscriptional Regulation ◽  
Cell Lymphoma ◽  
Dominant Role ◽  
Mrna Level ◽  
B Cell Lymphoma ◽  
Transcriptional Level ◽  
Bcl2 Protein

Abstract The regulation of B-cell lymphoma 2 (BCL2) protein expression in germinal center (GC) B cells has been controversial. Previous reports have indicated posttranscriptional regulation plays a dominant role. However, a number of recent studies contradicted these reports. Using real-time polymerase chain reaction (PCR) and Standardized Reverse Transcriptase-PCR (StaRT-PCR), we measured the level of mRNA expression in GC, mantle zone (MNZ), and marginal zone (MGZ) cells from laser capture microdissection. Both quantitative RT-PCR measurements of microdissected GC cells from tonsils showed that GC cells had low expression of BCL2 transcripts commensurate with the low protein expression level. These results are in agreement with microarray studies on fluorescence-activated cell sorter (FACS)-sorted cells and microdissected GC cells. We also examined BCL2 mRNA and protein expression on a series of 30 cases of diffuse large B-cell lymphoma (DLBCL) and found, in general, a good correlation. The results suggested that BCL2 protein expression is regulated at the transcriptional level in normal B cells and in the neoplastic cells in most B-cell lymphoproliferative disorders.

3-Ketoglutarate generation in pancreatic B-cell mitochondria regulates insulin secretory action of amino acids and 2-keto acids

1986 ◽  
Vol 6 (2) ◽  
pp. 163-169 ◽  
Author(s):  
S. Lenzen ◽  
W. Schmidt ◽  
I. Rustenbeck ◽  
U. Panten
Keyword(s):  
Amino Acids ◽  
Insulin Secretion ◽  
B Cell ◽  
Common Denominator ◽  
Pancreatic B Cell ◽  
Stimulate Insulin Secretion ◽  
Neutral Amino Acids ◽  
Keto Acids ◽  
Secretory Action ◽  
Pancreatic B Cells

The various neutral amino acids and aliphatic 2-keto acids exhibit differential effects on insulin secretion. The common denominator for all these effects is the 2-ketoglutarate generation in the pancreatic B-cell mitochondria. The neutral amino acids l-leucine and l-norvaline and the aliphatic ketomonocarboxylic acids 2-ketoisocaproate, 2-ketocaproate, 2-ketovalerate, and 2-keto-3-methylvalerate all stimulate insulin secretion and increase 2-ketoglutarate generation in pancreatic B-cell mitochondria through activation of glutamate dehydrogenase and transamination with l-glutamate and l-glutamine, respectively. The neutral amino acids l-valine, l-norleucine, and l-alanine and the aliphatic 2-keto acids 2-ketoisovalerate and pyruvate do not stimulate insulin secretion and do not increase 2-ketoglutarate generation in pancreatic B-cell mitochondria. Inhibition of 2-keto acid induced insulin secretion by l-valine and l-isoleucine is accompanied by reduced 2-ketoglutarate generation in pancreatic B-cell mitochondria. Thus intramitochondrial 2-ketoglutarate generation in pancreatic B-cells may regulate the insulin secretory potency of amino acids and 2-keto acids.

P724Antibody treatment against pathological pancreatic islet amyloid polypeptide (IAPP) aggregates restores endothelial dysfunction in human-IAPP transgenic rats

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Taheri ◽  
P Doytcheva ◽  
E Tarasco ◽  
W Gut ◽  
M Engeli ◽  
...  
Keyword(s):  
B Cells ◽  
Endothelial Dysfunction ◽  
Glucose Tolerance ◽  
B Cell ◽  
Aortic Arch ◽  
Islet Amyloid Polypeptide ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Islet Amyloid ◽  
Pancreatic B Cells

Abstract Background Islet amyloid polypeptide (IAPP; or amylin) is produced in pancreatic B-cells and co-secreted with insulin in response to nutrients. In insulin resistance and type 2 diabetes (T2D), higher secretion and impaired processing of IAPP results in its aggregation, contributing to amyloid-induced apoptosis of pancreatic B-cells. Insight into IAPP's role in diabetic endothelial dysfunction is scarce. Purpose Rats transgenic for human IAPP (hIAPP), which in contrast to rodent IAPP produces amyloid deposits and contributes to diabetes due to B-cell failure, were studied to understand the mechanisms of endothelial dysfunction in T2D and test the vasoprotective actions of an anti-hIAPP antibody. Methods Male hemizygous transgenic Sprague-Dawley rats with islet B-cell expression of hIAPP (TG) and wild-type (WT) controls were sacrificed at 2, 3, 6- and 9-months age to assess endothelial function. In a second experiment, TG rats received weekly injections of antibody against aggregated hIAPP (3 mg/kg; TG-Ab) from 3–12 months of age; TG and WT controls received PBS. Oral glucose tolerance was assessed before harvesting. At the respective time points (12 mts in exp. 2), thoracic aortic rings were isolated and subjected to ex vivo isometric tension recording. After contraction with norepinephrine (NE 1x10–7 mol/L), cumulative relaxation responses were performed to glucagon-like peptide-1 (GLP-1; 10–12 to 10–6 mol/L) and insulin (10–11 to 10–6 mol/L). Pancreas and aortic arch samples were used for immunostaining of hIAPP antibody engagement. Results GLP-1 and insulin-mediated vasodilation was impaired in 3 month-old TG rats compared to WT. Glucose intolerance appeared in TG rats at 6 months in comparison to WT (p<0.0001), indicating that endothelial dysfunction in TG rats precedes the onset of glucose intolerance. Anti-hIAPP antibody showed selectivity against aggregated IAPP in pancreatic islets, but there was no target engagement in the aortic arch, questioning a pathogenic role of IAPP deposition in the aortic wall. At 12 months, glucose control in TG-Ab rats was improved in comparison to TG control rats (p<0.013). Vasodilatation in TG-Ab rats was restored in response to GLP-1 (35.5% ± 4.6 vs. 16.0% ± 3.1 in TG controls), similar to that of WT rats (35.5% ± 6.5). Vasodilatation in response to insulin (48.9% ± 4.2) was improved in comparison to both TG (29.4% ± 3.0) and WT controls (32.5% ± 5.7) (p<0.0001; 2-way ANOVA, n=6–11 for all groups. Conclusion Early endothelial dysfunction develops in hIAPP rats compared to WT. Endothelial dysfunction is restored by the anti-hIAPP antibody treatment via improved oral glucose tolerance, but it remains unclear whether this effect is due to a local action in the aorta or a secondary effect, e.g. due to a reduction in pancreatic IAPP deposition.

Recovery of Glucose-Induced Insulin Secretion in a Rat Model of NIDDM Is Not Accompanied by Return of the B-Cell GLUT2 Glucose Transporter

Diabetes ◽  
1992 ◽  
Vol 41 (10) ◽  
pp. 1320-1327 ◽  
Author(s):  
C. Chen ◽  
B. Thorens ◽  
S. Bonner-Weir ◽  
G. C. Weir ◽  
J. L. Leahy
Keyword(s):  
Insulin Secretion ◽  
B Cell ◽  
Rat Model ◽  
Glucose Transporter ◽  
Glut2 Glucose Transporter

Fast insulin secretion reflects exocytosis of docked granules in mouse pancreatic B-cells

2002 ◽  
Vol 444 (1-2) ◽  
pp. 43-51 ◽  
Author(s):  
Charlotta S. Olofsson ◽  
Sven O. Göpel ◽  
Sebastian Barg ◽  
Juris Galvanovskis ◽  
Xiaosong Ma ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
B Cells ◽  
Pancreatic B Cells ◽  
Fast Insulin

scholarly journals Activation of alpha-2-adrenoceptors results in an increase in F-actin formation in HIT-T15 pancreatic B-cells

1995 ◽  
Vol 307 (1) ◽  
pp. 169-174 ◽  
Author(s):  
H C Cable ◽  
A el-Mansoury ◽  
N G Morgan
Keyword(s):  
Plasma Membrane ◽  
Insulin Secretion ◽  
B Cells ◽  
Fluorescence Microscopy ◽  
Pertussis Toxin ◽  
Actin Polymerization ◽  
Secretory Granules ◽  
Rhodamine Phalloidin ◽  
Late Step ◽  
Pancreatic B Cells

1. Alpha-2-adrenoceptor agonists, such as noradrenaline, are potent inhibitors of insulin secretion, and it has been suggested that they control a late step in the pathway of exocytosis. We have investigated whether this could be related to a change in the extent of actin polymerization in the pancreatic B-cell, since actin microfilaments are implicated in regulating the access of secretory granules to the plasma membrane prior to exocytosis. 2. Cultured HIT-T15 pancreatic B-cells responded to noradrenaline with an increase in F-actin content, as judged by a rise in the fluorescence output after probing of the cells with phalloidin (a toxin which binds specifically to F-actin) conjugated to rhodamine. The response to noradrenaline was rapid, dose-dependent and sustained and could be reproduced by the highly selective alpha-2-agonist UK14,304. Examination of HIT-T15 cells by fluorescence microscopy after treatment with rhodamine-phalloidin, revealed a significant localization of F-actin immediately adjacent to the plasma membrane. The pattern of F-actin distribution in the cells was not altered dramatically by noradrenaline, although the intensity of staining close to the plasma membrane appeared to be slightly reduced. 3. The increase in F-actin content induced by noradrenaline and UK14,304 was inhibited significantly by the alpha-2-antagonist idazoxan but not by the alpha-1-selective antagonist prazosin. Pretreatment of HIT-T15 cells with pertussis toxin did not lead to any direct alteration in F-actin content, although the toxin significantly modified the responses induced by noradrenaline and UK14,304. In each case, cells incubated for 24 h with pertussis toxin responded to the alpha-2-agonist with an enhanced fluorescence output, indicating that F-actin levels had increased still further. This did not correlate with any gross change in the distribution of F-actin as judged by fluorescence microscopy. 4. The results demonstrate that alpha-2-adrenoceptors are coupled to control of actin polymerization in HIT-T15 cells. They suggest that regulation of F-actin formation could be a component of the mechanism by which alpha-2-agonists mediate inhibition of insulin secretion.

scholarly journals LOCALIZATION OF ACID PHOSPHATASE ACTIVITY AND SECRETION MECHANISM IN RABBIT PANCREATIC B-CELLS

1966 ◽  
Vol 14 (3) ◽  
pp. 233-246 ◽  
Author(s):  
SYDNEY S. LAZARUS ◽  
BRUNO W. VOLK ◽  
HERBERT BARDEN
Keyword(s):  
Acid Phosphatase ◽  
B Cells ◽  
B Cell ◽  
Phosphatase Activity ◽  
Acid Phosphatase Activity ◽  
Secretory Granules ◽  
Secretory Product ◽  
Cell Cytoplasm ◽  
Single Membrane ◽  
Pancreatic B Cells

Utilizing formaldehyde- or glutaraldehyde-fixed tissue and Gomori's lead method it was found by optical microscopy that rabbit pancreatic islet cell acid phosphatase activity is present in discrete, mostly perinuclear foci and that this distribution differs from that of the aldehyde fuchsin-positive secretory granules which are densely packed at the capillary pole of the cell. Electron microscopically lead reaction product was noted in dense bodies, as well as in structures thought to be Golgi vacuoles and vesicles, it was also present in the innermost of the Golgi cisternae, and at the periphery of adjacent single membrane-limited bodies whose origin can be traced from the proximal cisternae. These latter bodies in routinely prepared, osmium-fixed material show finely granular content, which is in contrast to the electron-dense, central body seen in secretory granules that appear to originate from endoplasmic reticulum. B-cell cytoplasm contained additional numerous, single membrane-limited vacuoles with pale content. These are thought also to represent secretion vacuoles but with insulin secretory product in a different physical or chemical state. The lack of acid phosphatase activity in B-cell secretion vacuoles, the dissimilarities in fine structure between the content of secretory elements and that of the Golgi-derived granular body, together with previous evidence that alteration in B-cell functional state does not result in altered number or distribution of acid phosphatase active elements in B-cell cytoplasm, indicate a lack of relationship between acid phosphatase and secretory granule formation or release in pancreatic B-cells. It is also hypothesized that the secretory vacuole with central dense granule may be a storage form while the pale vacuole is the one which liberates its content to the intercellular space.

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