Insulin secretion and differential gene expression in glucose-responsive and -unresponsive MIN6 sublines.
We have established two sublines derived from the insulin-secreting mouse pancreatic beta-cell line MIN6, designated m9 and m14. m9 Cells exhibit glucose-induced insulin secretion in a concentration-dependent manner, whereas m14 cells respond poorly to glucose. In m14 cells, glucose consumption and lactate production are enhanced, and ATP production is largely through nonoxidative pathways. Moreover, lactate dehydrogenase activity is increased, and hexokinase replaces glucokinase as a glucose-phosphorylating enzyme. The ATP-sensitive K(+) channel activity and voltage-dependent calcium channel activity in m14 cells are reduced, and the resting membrane potential is significantly higher than in m9 cells. Thus, in contrast to m9, a model for beta-cells with normal insulin response, m14 is a model for beta-cells with impaired glucose-induced insulin secretion. By mRNA differential display of these sublines, we found 10 genes to be expressed at markedly different levels. These newly established MIN6 cell sublines should be useful tools in the analysis of the genetic and molecular basis of impaired glucose-induced insulin secretion.
Minami
K
K
Department of Molecular Medicine, Chiba University Graduate School of Medicine, Chiba 260 - 8670, Japan.
Yano
H
H
Miki
T
T
Nagashima
K
K
Wang
C Z
CZ
Tanaka
H
H
Miyazaki
J I
JI
Seino
S
S
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001692:Biological Transport / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002460:Cell Line; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D051273:Glucose Transporter Type 2; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D015220:Calcium Channels; D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D015221:Potassium Channels; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D005947:Glucose; D002118:Calcium