Regulation of β-Cell GK Gene Transcription by Insulin

2004 ◽  
pp. 249-261 ◽  
Author(s):  
B. Leibiger ◽  
P.-O. Berggren ◽  
I.B. Leibiger
Keyword(s):  
Beta Cell ◽  
Gene Transcription

scholarly journals Islet-specific Prmt5 excision leads to reduced insulin expression and glucose intolerance in mice

2020 ◽  
Vol 244 (1) ◽  
pp. 41-52
Author(s):  
Jian Ma ◽  
Xin He ◽  
Yan Cao ◽  
Kienan O’Dwyer ◽  
Katherine M Szigety ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Mouse Model ◽  
Beta Cell ◽  
Impaired Glucose Tolerance ◽  
Beta Cells ◽  
Gene Transcription ◽  
Insulin Gene ◽  
Beta Cell Proliferation ◽  
Arginine Methyltransferase

Protein arginine methyltransferase 5 (PRMT5), a symmetric arginine methyltransferase, regulates cell functions by influencing gene transcription through posttranslational modification of histones and non-histone proteins. PRMT5 interacts with multiple partners including menin, which controls beta cell homeostasis. However, the role of Prmt5 in pancreatic islets, particularly in beta cells, remains unclear. A mouse model with an islet-specific knockout (KO) of the Prmt5 gene was generated, and the influence of the Prmt5 excision on beta cells was investigated via morphologic and functional studies. Beta cell function was evaluated by glucose tolerance test (GTT) and glucose-stimulated insulin secretion (GSIS) test. Beta cell proliferation was evaluated by immunostaining. Gene expression change was determined by real-time qPCR. Molecular mechanisms were investigated in beta cells in vitro and in vivo in Prmt5 KO mice. The results show that islet-specific KO of Prmt5 reduced expression of the insulin gene and impaired glucose tolerance and GSIS in vivo. The mechanistic study indicated that PRMT5 is involved in the regulation of insulin gene transcription, likely via histone methylation-related chromatin remodeling. The reduced expression of insulin in beta cells in the Prmt5 KO mice may contribute to impaired glucose tolerance (IGT) and deficient GSIS in the mouse model. These results will provide new insights into exploring novel strategies to treat diabetes caused by insulin insufficiency.

scholarly journals Prolactin induction of insulin gene expression: the roles of glucose and glucose transporter-2

2000 ◽  
Vol 164 (3) ◽  
pp. 277-286 ◽  
Author(s):  
A Petryk ◽  
D Fleenor ◽  
P Driscoll ◽  
M Freemark
Keyword(s):  
Gene Expression ◽  
Beta Cell ◽  
Gene Transcription ◽  
Glucose Transporter ◽  
Insulin Gene ◽  
Luciferase Reporter ◽  
Insulin Production ◽  
Glucose Transporter 2 ◽  
Insulin Gene Expression ◽  
Insulin Gene Transcription

Previous studies have shown that lactogenic hormones stimulate beta-cell proliferation and insulin production in pancreatic islets. However, all such studies have been conducted in cells incubated in medium containing glucose. Since glucose independently stimulates beta-cell replication and insulin production, it is unclear whether the effects of prolactin (PRL) on insulin gene expression are exerted directly or through the uptake and/or metabolism of glucose. We examined the interactions between glucose and PRL in the regulation of insulin gene transcription and the expression of glucose transporter-2 (glut-2) and glucokinase mRNAs in rat insulinoma (INS-1) cells. In the presence of 5.5 mM glucose, the levels of preproinsulin and glut-2 mRNAs in PRL-treated cells exceeded the levels in control cells (1.7-fold, P<0.05 and 2-fold, P<0.05 respectively). The maximal effects of PRL were noted at 24-48 h of incubation. PRL had no effect on the levels of glucokinase mRNA. The higher levels of glut-2 mRNA were accompanied by an increase in the number of cellular glucose transporters, as demonstrated by a 1. 4- to 2.4-fold increase in the uptake of 2-deoxy-d-[(3)H]glucose in PRL-treated INS-1 cells (P<0.001). These findings suggested that the insulinotropic effect of PRL is mediated, in part, by induction of glucose transport and/or glucose metabolism. Nevertheless, even in the absence of glucose, PRL stimulated increases in the levels of preproinsulin mRNA (3.4-fold higher than controls, P<0.0001) and glut-2 mRNA (2-fold higher than controls, P<0.01). These observations suggested that PRL exerts glucose-independent as well as glucose-dependent effects on insulin gene expression. Support for this hypothesis was provided by studies of insulin gene transcription using INS-1 cells transfected with a plasmid containing the rat insulin 1 promoter linked to a luciferase reporter gene. Glucose and PRL, alone and in combination, stimulated increases in cellular luciferase activity. The relative potencies of glucose (5.5 mM) alone, PRL alone, and glucose plus PRL in combination were 2.2 (P<0.001), 3.4 (P<0.01), and 7.9 (P<0.0001) respectively. Our findings suggest that glucose and PRL act synergistically to induce insulin gene transcription.

scholarly journals Ectopic expression of the beta-cell specific transcription factor Pdx1 inhibits glucagon gene transcription

Diabetologia ◽  
2003 ◽  
Vol 46 (6) ◽  
pp. 810-821 ◽  
Author(s):  
B. Ritz-Laser ◽  
B. R. Gauthier ◽  
A. Estreicher ◽  
A. Mamin ◽  
T. Brun ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Beta Cell ◽  
Gene Transcription ◽  
Ectopic Expression ◽  
Specific Transcription Factor

Activator protein-1 is necessary for angiotensin-II stimulation of human adrenocorticotropin receptor gene transcription

2001 ◽  
Vol 268 (6) ◽  
pp. 1802-1810
Author(s):  
Danielle Naville ◽  
Estelle Bordet ◽  
Marie-Claude Berthelon ◽  
Philippe Durand ◽  
Martine Begeot
Keyword(s):  
Angiotensin Ii ◽  
Gene Transcription ◽  
Receptor Gene ◽  
Activator Protein 1 ◽  
Activator Protein ◽  
Stimulation Of
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