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 Adiponectin-induced ERK and Akt Phosphorylation Protects against Pancreatic Beta Cell Apoptosis and Increases Insulin Gene Expression and Secretion

2010 ◽  
Vol 285 (44) ◽  
pp. 33623-33631 ◽  
Author(s):  
Nadeeja Wijesekara ◽  
Mansa Krishnamurthy ◽  
Alpana Bhattacharjee ◽  
Aamir Suhail ◽  
Gary Sweeney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Beta Cell ◽  
Cell Apoptosis ◽  
Pancreatic Beta Cell ◽  
Insulin Gene ◽  
Beta Cell Apoptosis ◽  
Akt Phosphorylation ◽  
Insulin Gene Expression

scholarly journals Mitochondrial and insulin gene expression in single cells shape pancreatic beta cells’ population divergence

2020 ◽  
Author(s):  
H. Medini ◽  
T. Cohen ◽  
D. Mishmar
Keyword(s):  
Gene Expression ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Single Cells ◽  
Insulin Gene ◽  
Population Divergence ◽  
Cell Populations ◽  
Alpha Cells ◽  
Insulin Gene Expression

AbstractMitochondrial gene expression is pivotal to cell metabolism. Nevertheless, it is unknown whether it diverges within a given cell type. Here, we analysed single-cell RNA-seq experiments from ∼4600 human pancreatic alpha and beta cells, as well as ∼900 mouse beta cells. Cluster analysis revealed two distinct human beta cells populations, which diverged by mitochondrial (mtDNA) and nuclear DNA (nDNA)-encoded oxidative phosphorylation (OXPHOS) gene expression in healthy and diabetic individuals, and in newborn but not in adult mice. Insulin gene expression was elevated in beta cells with higher mtDNA gene expression in humans and in young mice. Such human beta cell populations also diverged in mt-RNA mutational repertoire, and in their selective signature, thus implying the existence of two previously overlooked distinct and conserved beta cell populations. While applying our approach to alpha cells, two sub-populations of cells were identified which diverged in mtDNA gene expression, yet these cellular populations did not consistently diverge in nDNA OXPHOS genes expression, nor did they correlate with the expression of glucagon, the hallmark of alpha cells. Thus, pancreatic beta cells within an individual are divided into distinct groups with unique metabolic-mitochondrial signature.

scholarly journals Genetically Engineered Insulin Mediated by Glucose Transporter-2 (GLUT2) Promoter for the Biosynthesis of Insulin in Rat Hepatocytes: Insulin Gene Therapy

2021 ◽  
Author(s):  
Gehad Abdallah
Keyword(s):  
Gene Therapy ◽  
Pancreatic Beta Cells ◽  
Glucose Transporter ◽  
Glucose Sensing ◽  
Genetically Engineered ◽  
Insulin Gene ◽  
Site Directed Mutagenesis ◽  
Target Cells ◽  
Insulin Production ◽  
Glucose Transporter 2

Abstract Background: Expression of insulin in hepatocytes by hepatic gene therapy is a promising treatment of diabetes. The conversion of immature proinsulin to mature insulin occurs only in cells that contain the enzymes responsible for the cleavage of proinsulin to insulin.Results: I engineered rat proinsulin with the sites of cleavage (Furin Cleavable Sites) using site directed mutagenesis for removal of C-peptide to form the two chains A and B for mature insulin production. This engineered proinsulin was constructed into a non-viral expressing vector and regulated by glucose transporter-2 promoter to control the amount of mature insulin expressed, and to modulate the amount of glucose found in hepatocytes. The mature, active and regulated expressed insulin was secreted according to the amount of glucose regulated by the glucose transporter-2 promoter. Concolusion: For successful hepatic insulin gene therapy, insulin production must be tightly coupled to glucose concentration. Hepatocytes are excellent target cells for insulin gene therapy since, they are similar to pancreatic beta cells, they have the ability to rapidly adapt to blood glucose concentrations as they possess glucose-sensing components, such as Glucose Transporter-2.

TLR2/6 and TLR4-activated macrophages contribute to islet inflammation and impair beta cell insulin gene expression via IL-1 and IL-6

Diabetologia ◽  
2014 ◽  
Vol 57 (8) ◽  
pp. 1645-1654 ◽  
Author(s):  
Dominika Nackiewicz ◽  
Meixia Dan ◽  
Wei He ◽  
Rosa Kim ◽  
Anisa Salmi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Beta Cell ◽  
Insulin Gene ◽  
Activated Macrophages ◽  
Insulin Gene Expression ◽  
Islet Inflammation

scholarly journals Function and Gene Expression of Islets Experimentally Transplanted to Muscle and Omentum

2020 ◽  
Vol 29 ◽  
pp. 096368972096018
Author(s):  
Daniel Espes ◽  
Hanna Liljebäck ◽  
Petra Franzén ◽  
My Quach ◽  
Joey Lau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Glucose ◽  
Beta Cell ◽  
Islet Transplantation ◽  
Glucose Transporter ◽  
Cell Function ◽  
Greater Omentum ◽  
Intravenous Glucose ◽  
Glucose Transporter 2 ◽  
Implantation Sites

Islet transplantation to the liver is a potential curative treatment for patients with type 1 diabetes. Muscle and the greater omentum are two alternative implantation sites, which can provide excellent engraftment and hold potential as future sites for stem-cell-derived beta-cell replacement. We evaluated the functional outcome after islet transplantation to muscle and omentum and found that alloxan-diabetic animals were cured with a low number of islets (200) at both sites. The cured animals had a normal area under the curve blood glucose response to intravenous glucose, albeit animals with intramuscular islet grafts had increased 120-min blood glucose levels. They also demonstrated an exaggerated counter regulatory response to hypoglycemia. The expression of genes important for beta-cell function was, at both implantation sites, comparable to that in native pancreatic islets. The gene expression of insulin (INS1 and INS2) and glucose transporter-2 was even increased, and the expression of lactate dehydrogenase decreased, at both sites when compared to native islets. We conclude that muscle and omentum provide excellent conditions for engraftment of transplanted islets. When compared to control, 200 islets implanted to the omentum displayed a restored glucose tolerance, whereas animals with intramuscular islet grafts of similar size displayed mild glucose intolerance.

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