Characterization of a novel glucose-responsive insulin-secreting cell line, BRIN-BD11, produced by electrofusion

McClenaghan, Neville H.; Barnett, Christopher R.; Ah-Sing, E.; Abdel-Wahab, Y. H.; O’Harte, Finbarr; Yoon, T. W.; Swanston-Flatt, Sara K.; Flatt, Peter R.

doi:10.2337/diabetes.45.8.1132

Cited by 168 publications

(200 citation statements)

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“…1.1B4 cells showed a more enhanced stepwise pattern of insulin output when compared with 1.1E7 and 1.4E7 cells, releasing about 10% of their insulin content, similar to the pattern observed in several animal beta cell lines (1,7). This insulin secretory effect was potentiated by a further 20 -60% when glucose was combined with the phosphodiesterase inhibitor IBMX.…”

Section: Discussionsupporting

confidence: 48%

“…The fusion and cloning techniques were carefully optimized in our laboratory to produce hybrids inheriting beta cell attributes and immortality from the two cell fusion partners. A similar approach was used to produce glucose-responsive rat insulin-secreting cells previously (7).…”

Section: Discussionmentioning

confidence: 99%

“…RIN cell lines derived from a transplantable rat insulinoma (6) have been used extensively, and a number of derived cell lines have been generated from their subclones. One of these is the glucose-responsive insulin-secreting BRIN-BD11 cell line generated by electrofusion of the RINm5F clone and normal rat beta cells (7). The INS-1 cell line (8), also derived from the original radiation tumor, has high insulin content and is able to maintain insulin secretory responsiveness over a prolonged period in culture (6).…”

mentioning

confidence: 99%

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Development and Functional Characterization of Insulin-releasing Human Pancreatic Beta Cell Lines Produced by Electrofusion

McCluskey

Hamid

Guo-Parke

et al. 2011

Journal of Biological Chemistry

134

103

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Three novel human insulin-releasing cell lines designated 1.1B4, 1.4E7, and 1.1E7 were generated by electrofusion of freshly isolated of human pancreatic beta cells and the immortal human PANC-1 epithelial cell line. Functional studies demonstrated glucose sensitivity and responsiveness to known modulators of insulin secretion. Western blot, RT-PCR, and immunohistochemistry showed expression of the major genes involved in proinsulin processing and the pancreatic beta cell stimulussecretion pathway including PC1/3, PC2, GLUT-1, glucokinase, and K-ATP channel complex (Sur1 and Kir6.2) and the voltagedependent L-type Ca 2؉ channel. The cells stained positively for insulin, and 1.1B4 cells were used to demonstrate specific staining for insulin, C-peptide, and proinsulin together with insulin secretory granules by electron microscopy. Analysis of metabolic function indicated intact mechanisms for glucose uptake, oxidation/utilization, and phosphorylation by glucokinase. Glucose, alanine, and depolarizing concentrations of K ؉ were all able to increase [Ca 2؉ ] i in at least two of the cell lines tested. Insulin secretion was also modulated by other nutrients, hormones, and drugs acting as stimulators or inhibitors in normal beta cells. Subscapular implantation of the 1.1B4 cell line improved hyperglycemia and resulted in glucose lowering in streptozotocin-diabetic SCID mice. These novel human electrofusion-derived beta cell lines therefore exhibit stable characteristics reminiscent of normal pancreatic beta cells, thereby providing an unlimited source of human insulin-producing cells for basic biochemical studies and pharmacological drug testing plus proof of concept for cellular insulin replacement therapy.

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Development and Functional Characterization of Insulin-releasing Human Pancreatic Beta Cell Lines Produced by Electrofusion

McCluskey

Hamid

Guo-Parke

et al. 2011

Journal of Biological Chemistry

134

103

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“…Insulin release was determined using monolayers of BRIN-BD11 clonal pancreatic cells (15) . BRIN-BD11 cells were grown in Roswell Park Memorial Institute (RPMI) 1640 tissue culture medium containing 11·1 mM-glucose, 10 % fetal calf serum and antibiotics (50 000 IU penicillinstreptomycin/litre), and maintained at 378C in an atmosphere of 5 % CO 2 and 95 % air.…”

Section: Insulin Secretionmentioning

confidence: 99%

Terminalia belliricastimulates the secretion and action of insulin and inhibits starch digestion and protein glycationin vitro

Kasabri

Flatt²,

Abdel-Wahab³

2009

Br J Nutr

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Traditional plant treatments have been used throughout the world for the therapy of diabetes mellitus. The aim of the present study was to investigate the efficacy and mode of action of Terminalia bellirica used traditionally for the treatment of diabetes in India. T. bellirica aqueous extract stimulated basal insulin output and potentiated glucose-stimulated insulin secretion concentration-dependently in the clonal pancreatic β-cell line, BRIN-BD11 (P < 0·001). The insulin-secretory activity of the plant extract was abolished in the absence of extracellular Ca2+ and by inhibitors of cellular Ca2+ uptake, diazoxide and verapamil (P < 0·001; n 8). Furthermore, the extract did not increase insulin secretion in depolarised cells and did not further augment insulin secretion triggered by tolbutamide or glibenclamide. T. bellirica extract also displayed insulin-mimetic activity and enhanced insulin-stimulated glucose uptake in 3T3-L1 adipocytes by 300 %. At higher concentrations, the extract also produced a 10–50 % (P < 0·001) decrease in starch digestion in vitro and inhibited protein glycation (P < 0·001). The present study has revealed that components in T. bellirica extract stimulate insulin secretion, enhance insulin action and inhibit both protein glycation and starch digestion. The former actions are dependent on the active principle(s) in the plant being absorbed intact. Future work assessing the use of T. bellirica as a dietary adjunct or as a source of active anti-diabetic agents may provide new opportunities for the treatment of diabetes.

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“…In vitro insulin secretion BRIN-BD11 cells were used to assess the insulin-releasing activity of test peptides, as described previously [30]. This hybrid cell line (ECACC 10033003) was originally generated in-house by electrofusion of a primary culture of New England Deaconess Hospital (NEDH) rat pancreatic islets with RINm5F (a cell line derived from an NEDH rat insulinoma), and has been mycoplasma eradicated.…”

Section: Methodsmentioning

confidence: 99%

An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity, enhances beta cell function and improves glucose homeostasis in high-fat-fed mice

Hasib

Gault

et al. 2016

Diabetologia

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Aims/hypothesis Glucose-dependent insulinotropic polypeptide (GIP) and xenin, regulatory gut hormones secreted from enteroendocrine K cells, exert important effects on metabolism. In addition, xenin potentiates the biological actions of GIP. The present study assessed the actions and therapeutic utility of a (DAla 2 )GIP/xenin-8-Gln hybrid peptide, in comparison with the parent peptides (DAla 2 )GIP and xenin-8-Gln. Methods Following confirmation of enzymatic stability, insulin secretory activity of (DAla 2 )GIP/xenin-8-Gln was assessed in BRIN-BD11 beta cells. Acute and persistent glucose-lowering and insulin-releasing effects were then examined in vivo. Finally, the metabolic benefits of twice daily injection of (DAla 2 )GIP/xenin-8-Gln was determined in high-fat-fed mice.

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Characterization of a novel glucose-responsive insulin-secreting cell line, BRIN-BD11, produced by electrofusion

Cited by 168 publications

References 0 publications

Development and Functional Characterization of Insulin-releasing Human Pancreatic Beta Cell Lines Produced by Electrofusion

Development and Functional Characterization of Insulin-releasing Human Pancreatic Beta Cell Lines Produced by Electrofusion

Terminalia belliricastimulates the secretion and action of insulin and inhibits starch digestion and protein glycationin vitro

An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity, enhances beta cell function and improves glucose homeostasis in high-fat-fed mice

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