Murine Insulinoma Cell Line With Normal Glucose-Regulated Insulin Secretion

Pancreatic βTC lines derived from insulinomas arising in transgenic mice expressing SV40 Tag under control of the insulin promoter manifest a differentiated β-cell phenotype and secrete insulin in response to glucose. Previously reported βTC lines respond to subphysiological extracellular glucose levels compared with normal β-cells. Recently, several βTC lines were developed with normal glucose-regulated insulin secretion from insulinomas obtained by breeding of the RIP-Tag transgene from the original C57BI/6 mouse strain into the C3HeB/FeJ strain. One of these βTC lines, βTC7, was characterized in detail. βTC7 cells express GLUT2 and have levels of glucokinase and hexokinase activity similar to those of normal islets. As a result these cells exhibit a normal glucose concentration dependency for glycolysis and insulin secretion, thus representing an accurate model of β-cell function. On continuous propagation in culture, βTC7 cells acquired a response to lower extracellular glucose levels. This change was associated with a fourfold increase in hexokinase activity, without significant changes in glucokinase activity and glucose uptake rates. These findings suggest an important role for glucose phosphorylation rates in regulation of the β-cell insulin secretory response to glucose.

[1]  D. Hanahan,et al.  Glucose transporter isotypes switch in T-antigen-transformed pancreatic beta cells growing in culture and in mice , 1992, Molecular and cellular biology.

[2]  C B Wollheim,et al.  Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines. , 1992, Endocrinology.

[3]  K. Hamaguchi,et al.  NIT-1, a Pancreatic β-Cell Line Established From a Transgenic NOD/Lt Mouse , 1991, Diabetes.

[4]  H. Najafi,et al.  Glucose regulates glucokinase activity in cultured islets from rat pancreas. , 1990, The Journal of biological chemistry.

[5]  J. Miyazaki,et al.  Establishment of a pancreatic beta cell line that retains glucose-inducible insulin secretion: special reference to expression of glucose transporter isoforms. , 1990, Endocrinology.

[6]  S. Efrat,et al.  Regulation of Insulin Secretion from β-Cell Lines Derived from Transgenic Mice Insulinomas Resembles that of Normal β-Cells* , 1990 .

[7]  J. H. Johnson,et al.  The high Km glucose transporter of islets of Langerhans is functionally similar to the low affinity transporter of liver and has an identical primary sequence. , 1990, The Journal of biological chemistry.

[8]  G I Bell,et al.  Molecular Biology of Mammalian Glucose Transporters , 1990, Diabetes Care.

[9]  H. Lodish,et al.  Molecular Physiology of Glucose Transporters , 1990, Diabetes Care.

[10]  D. Hanahan,et al.  Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[11]  H. Najafi,et al.  Glucose Transport by Radiation-Induced Insulinoma and Clonal Pancreatic β-Cells , 1986, Diabetes.

[12]  F. Matschinsky,et al.  Pancreatic islet glucose metabolism and regulation of insulin secretion. , 1986, Diabetes/metabolism reviews.

[13]  D. Hanahan,et al.  Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. , 1985, Nature.

[14]  J. Nielsen.  Growth and function of the pancreatic beta cell in vitro: effects of glucose, hormones and serum factors on mouse, rat and human pancreatic islets in organ culture. , 1985, Acta endocrinologica. Supplementum.

[15]  D. Pipeleers,et al.  Differences in glucose handling by pancreatic A- and B-cells. , 1983, The Journal of biological chemistry.

[16]  F. Matschinsky,et al.  New perspectives on pancreatic islet glucokinase. , 1984, The American journal of physiology.

[17]  D. Williams,et al.  Insulin synthesis in a clonal cell line of simian virus 40-transformed hamster pancreatic beta cells. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[18]  S. Ashcroft.  6 – Metabolic Controls of Insulin Secretion , 1981 .

[19]  A. Gazdar,et al.  Continuous, clonal, insulin- and somatostatin-secreting cell lines established from a transplantable rat islet cell tumor. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[20]  S. Baum,et al.  The role of calcium in insulin release from hamster insulinoma cells. , 1977, Endocrinology.

[21]  W. Chick,et al.  A transplantable insulinoma in the rat. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[22]  G. Grodsky,et al.  Interrelationships Between α and β Anomers of Glucose Affecting both Insulin and Glucagon Secretion in the Perfused Rat Pancreas. II. , 1975 .

[23]  P. Maitra.  Glucokinase from yeast. , 1975, Methods in enzymology.

[24]  I. W. Mclean,et al.  PERIODATE-LYSINE-PARAFORMALDEHYDE FIXATIVE A NEW FIXATIVE FOR IMMUNOELECTRON MICROSCOPY , 1974, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[25]  H. Kirkman.  A preliminary report concerning tumors observed in Syrian hamsters. , 1962, Stanford medical bulletin.

[26]  B. Hofstee.  Non-Inverted Versus Inverted Plots in Enzyme Kinetics , 1959, Nature.

[27]  E. Webb,et al.  Non-Inverted Versus Inverted Plots in Enzyme Kinetics , 1959, Nature.

[28]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.