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.

Mechanisms of amino acid-induced insulin secretion from the glucose-responsive BRIN-BD11 pancreatic B-cell line

1996 ◽  
Vol 151 (3) ◽  
pp. 349-357 ◽  
Author(s):  
N H McClenaghan ◽  
C R Barnett ◽  
F P M O'Harte ◽  
P R Flatt
Keyword(s):  
Amino Acids ◽  
Insulin Secretion ◽  
Amino Acid ◽  
B Cell ◽  
Cell Line ◽  
Future Research ◽  
Nutrient Regulation ◽  
Pancreatic B Cell ◽  
Voltage Dependent ◽  
Pancreatic B Cells

Abstract The effects of different classes of amino acids known to be transported and utilized by pancreatic B-cells were examined using the novel glucose-responsive pancreatic B-cell line, BRIN-BD11. Amino acids tested included α-aminoisobutyric acid, l-alanine, l-arginine, l-glutamine, glycine, l-leucine, l-lysine, l-proline and l-serine. At non-stimulatory (1·1 mmol/l) glucose, acute incubations with either 1 or 10 mmol/l amino acid evoked 1·3- to 4·7-fold increases of insulin release. Raising glucose to 16·7 mmol/l enhanced the effects of all amino acids except l-glutamine, and increased insulin output at 10 mmol/l compared with 1 mmol/l amino acid. Glyceraldehyde (10 mmol/l) also served to promote 10 mmol/l amino acid-induced insulin secretion with the exceptions of l-arginine, glycine, l-lysine and l-proline. At 16·7 mmol/l glucose, diazoxide (300 μmol/l) significantly decreased the secretory response to all amino acids except l-glutamine. Likewise, verapamil (20 μmol/l) or depletion of extracellular Ca2+ reduced insulin output indicating the importance of Ca2+ influx in the actions of amino acids. These data indicate that BRIN-BD11 cells transport and utilize amino acids, acting in association with glycolysis, K+-ATP channels and/or voltage-dependent Ca2+ channels to promote Ca2+ influx and insulin secretion. The response of BRIN-BD11 cells to glucose and amino acids indicates that this is a useful cell line for future research on the mechanisms of nutrient regulation of insulin secretion. Journal of Endocrinology (1996) 151, 349–357

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.

Effect of glucose and amino acids on insulin-secretion from a novel pancreatic B-cell line produced by electrofusion

1994 ◽  
Vol 22 (2) ◽  
pp. 237S-237S
Author(s):  
NEVILLE H. McCLENAGHAN ◽  
TAI-WOOK YOON ◽  
CHRISTOPHER R. BARNETT ◽  
ALISON M. WILSON ◽  
YASSER H. A. ABDEL-WAHAB ◽  
...  
Keyword(s):  
Amino Acids ◽  
Insulin Secretion ◽  
B Cell ◽  
Cell Line ◽  
Pancreatic B Cell ◽  
Effect Of Glucose

scholarly journals Evidence for two different types of P2 receptors stimulating insulin secretion from pancreatic B cell

1998 ◽  
Vol 125 (6) ◽  
pp. 1368-1374 ◽  
Author(s):  
P Petit ◽  
D Hillaire-Buys ◽  
M Manteghetti ◽  
S Debrus ◽  
J Chapal ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
B Cell ◽  
P2 Receptors ◽  
Pancreatic B Cell ◽  
Different Types

scholarly journals SNAP-25 is expressed in islets of Langerhans and is involved in insulin release.

1995 ◽  
Vol 128 (6) ◽  
pp. 1019-1028 ◽  
Author(s):  
K Sadoul ◽  
J Lang ◽  
C Montecucco ◽  
U Weller ◽  
R Regazzi ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Insulin Secretion ◽  
B Cell ◽  
Insulin Release ◽  
Islet Cells ◽  
Secretory Granules ◽  
Cell Types ◽  
Pancreatic B Cell ◽  
Pancreatic Endocrine Cells ◽  
Presynaptic Plasma Membrane

SNAP-25 is known as a neuron specific molecule involved in the fusion of small synaptic vesicles with the presynaptic plasma membrane. By immunolocalization and Western blot analysis, it is now shown that SNAP-25 is also expressed in pancreatic endocrine cells. Botulinum neurotoxins (BoNT) A and E were used to study the role of SNAP-25 in insulin secretion. These neurotoxins inhibit transmitter release by cleaving SNAP-25 in neurons. Cells from a pancreatic B cell line (HIT) and primary rat islet cells were permeabilized with streptolysin-O to allow toxin entry. SNAP-25 was cleaved by BoNT/A and BoNT/E, resulting in a molecular mass shift of approximately 1 and 3 kD, respectively. Cleavage was accompanied by an inhibition of Ca(++)-stimulated insulin release in both cell types. In HIT cells, a concentration of 30-40 nM BoNT/E gave maximal inhibition of stimulated insulin secretion of approximately 60%, coinciding with essentially complete cleavage of SNAP-25. Half maximal effects in terms of cleavage and inhibition of insulin release were obtained at a concentration of 5-10 nM. The A type toxin showed maximal and half-maximal effects at concentrations of 4 and 2 nM, respectively. In conclusion, the results suggest a role for SNAP-25 in fusion of dense core secretory granules with the plasma membrane in an endocrine cell type- the pancreatic B cell.

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.

Abstract: 1043 HIGH DENSITY LIPOPROTEINS (HDL) INCREASE PANCREATIC B-CELL INSULIN SECRETION

2009 ◽  
Vol 10 (2) ◽  
pp. e403
Author(s):  
M Fryirs ◽  
P Barter ◽  
F Tabet ◽  
A Heather ◽  
K Rye
Keyword(s):  
Insulin Secretion ◽  
B Cell ◽  
High Density ◽  
High Density Lipoproteins ◽  
Pancreatic B Cell
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