An Inhibitory Role for Phosphatidylinositol 3-Kinase in Insulin Secretion from Pancreatic B Cell Line MIN6

1995 ◽  
Vol 214 (1) ◽  
pp. 51-59 ◽  
Author(s):  
S. Hagiwara ◽  
T. Sakurai ◽  
F. Tashiro ◽  
Y. Hashimoto ◽  
Y. Matsuda ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
B Cell ◽  
Cell Line ◽  
Phosphatidylinositol 3 Kinase ◽  
Pancreatic B Cell ◽  
Inhibitory Role ◽  
Phosphatidylinositol 3

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

Subcutaneous Xenotransplantation of Hybrid Artificial Pancreas Encapsulating Pancreatic B Cell Line (MIN6): Functional and Histological Study

1997 ◽  
Vol 6 (5) ◽  
pp. 541-545 ◽  
Author(s):  
Yoshiyuki Kawakami ◽  
Kazutomo Inoue ◽  
Hiroyuki Hayashi ◽  
W.j. Wang ◽  
Hiroshi Setoyama ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
B Cell ◽  
Cell Line ◽  
Histological Study ◽  
Artificial Pancreas ◽  
Bioartificial Pancreas ◽  
Glucose Stimulation ◽  
Min6 Cells ◽  
Pancreatic B Cell ◽  
Endocrine Tissues

The biohybrid artificial pancreas is designed to enclose pancreatic endocrine tissues with a selectively permeable membrane that immunoisolates the graft from the host immune system, allowing those endocrine tissues to survive and control glucose metabolism for an extended period of time. The pancreatic B cell line MIN6 is established from a pancreas B cell tumor occurring in transgenic mice harboring the human insulin promoter gene connected to the SV40 T-antigen hybrid gene. It has been proven that glucose-stimulated insulin secretion in MIN6 cells retains a concentration-dependent response similar to that of normal islets. In this study, we performed the histological and functional examination of three-layer microbeads employing MIN6 cells after subcutaneous xenotransplantation to evaluate this device as bioartificial pancreas. MIN6 cells were microencapsulated in three-layer microbeads formulated with agarose, polystyrene sulfonic acid, polybrene, and carboxymethyl cellulose. Microbeads were xenogenically implanted in the subcutaneous tissue of the back of Lewis rats with streptozotocin-induced diabetes. One week after implantation, microbeads were retrieved and cultured for 24 h before the static incubation. There was no evidence of adhesion to the graft and the fibrosis in the transplantation site as determined by gross visual inspection. Microscopic examination demonstrated that retrieved microbeads maintained normal shape, containing intact MIN6 cells. Histological study showed that these MIN6 cells in the microbeads appeared to be viable without cellular infiltration within or around the microbeads. Immunohistochemical analysis of the microbeads clearly revealed the intense staining of insulin in the cytoplasm of encapsulated MIN6 cells. Insulin productivity of MIN6 cells in the microbeads is strongly suggested to be preserved. In response to 16.7 mM glucose stimulation, static incubation of microbeads 1 wk after implantation caused the 2.3 times increase in insulin secretion seen after 3.3 mM glucose stimulation (84.3 ± 10.0 vs. 37.4 ± 10.7 μU/3 × 106 cells/hr, n = 5 each, p < 0.01). This study demonstrates that three-layer microbeads encapsulating MIN6 cells retain excellent biocompatibility and maintain good insulin secretion even after subcutaneous xenotransplantation, suggesting the possible future clinical application of this unique bioartificial pancreas to subcutaneous xenotransplantation.

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

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.

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