Effects of Media Conditions, Insulin, and Dexamethasone on Insulin-Receptor mRNA and Promoter Activity in HepG2 Cells

Levy, James R.; Krystal, Geoffrey W.; Glickman, Penny S.; Dastvan, Frank

doi:10.2337/diab.40.1.58

Cited by 16 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As tissue-specific differences in response occur alongside alterations in circulating insulin concentration, insulin may not be the only factor in the control of the level of insulin-receptor mRNA. Indeed, it has been demonstrated in vitro in human cell lines that insulin-receptor mRNA levels are reduced by depletion of glucose levels (Briata et al 1990;Levy et al 1991), but at present it is not possible to relate this observation to the situation in vivo described here.…”

Section: Discussionmentioning

confidence: 64%

Changes in insulin-receptor mRNA levels in skeletal muscle and brown adipose tissue of weanling rats during fasting and refeeding

Knott¹,

Trayhurn²,

Hesketh³

1992

Br J Nutr

View full text Add to dashboard Cite

Tissue-specific alterations in insulin sensitivity occur in response to fasting and refeeding, as part of the integrated adaptive mechanisms employed to adjust to major changes in nutritional status. In the present study the effects of fasting and refeeding on insulin-receptor, actin and myosin mRNA levels in skeletal muscle, and insulin-receptor and uncoupling-protein mRNA in brown adipose tissue of rats have been examined. Insulin-receptor mRNA levels increased markedly in both skeletal muscle and brown adipose tissue after a 40 h fast, the increase being greater in brown fat (8-fold) than in muscle (2-fold). On refeeding for 4 h, the insulin-receptor mRNA level in both tissues declined rapidly to control levels. An increase in insulin-receptor mRNA level was also observed in brown adipose tissue after a 16 h fast, although not in skeletal muscle. In contrast to the insulin-receptor mRNA, the level of the mRNA for the mitochondria1 uncoupling protein declined markedly in brown adipose tissue during a 40 h fast. These results indicate that insulin-receptor mRNA levels are modulated in response to the alterations in nutritional status that occur during fasting and refeeding; this may reflect a nutritional influence on transcription of the receptor-protein gene.

show abstract

Section: Discussionmentioning

confidence: 64%

Changes in insulin-receptor mRNA levels in skeletal muscle and brown adipose tissue of weanling rats during fasting and refeeding

Knott¹,

Trayhurn²,

Hesketh³

1992

Br J Nutr

View full text Add to dashboard Cite

show abstract

“…As expected from the short half-life (2-4 h) (20,24,43) of the insulin receptor mRNA, ACT D treatment of control rats led to a marked decrease, on Northern blots, in the intensity of both the 9.5 and 7.5 kb insulin receptor mRNA species (Fig. 1, right lane).…”

Section: Resultsmentioning

confidence: 70%

“…Based on ACT D and in vitro transcription studies, it has been shown previously that the stimulatory effect of glucocorticoids on insulin receptor mRNA in human IM-9 lymphocytes also occurs at the transcriptional level (24,43). It is not known, however, whether the insulin-induced decrease in insulin receptor mRNA levels seen in rat pancreatic acinar cells (19) and Hep G2 cells (20,21) also involves a change in receptor gene transcription.…”

Section: Discussionmentioning

confidence: 90%

“…Although in certain types of cells (10), receptors are lost from the cell surface merely by intemalization, in most cases, total cellular number decreases as a result of accelerated receptor degradation (16)(17)(18)(19). Evidence also exists that, in certain cell types, insulin may act by inhibiting receptor synthesis (19) and/or decreasing steady-state insulin receptor mRNA levels (19)(20)(21), although such effects have not been observed uniformly (17,18,(22)(23)(24)(25).…”

mentioning

confidence: 96%

See 1 more Smart Citation

Effects of STZ-Induced Diabetes and Fasting on Insulin Receptor mRNA Expression and Insulin Receptor Gene Transcription in Rat Liver

Tozzo

Desbuquois

1992

Diabetes

View full text Add to dashboard Cite

Insulinopenic states in rodents are known to cause an increase in the number of hepatic insulin receptors. To determine if this change is related to an abnormality in insulin receptor gene expression, insulin receptor binding, insulin receptor mRNA levels, and insulin receptor gene transcription rates have been measured in livers from rats rendered hypoinsulinemic by STZ administration (65 mg/kg) or fasting. In the two groups of experimental rats, insulin binding to liver plasma membranes was increased (approximately 40 and 25%, respectively) relative to control, normoinsulinemic animals. Northern blot analysis of either total or poly (A)+ RNA from livers of hypo- and normoinsulinemic rats revealed two major insulin receptor mRNA species of 9.5 and 7.5 kbs. In hypoinsulinemic rats, insulin receptor mRNA levels were increased > or = 10-fold, with similar effects on the two mRNA species. The effects of STZ administration and fasting on insulin receptor binding and insulin receptor mRNA levels were fully reversed by insulin treatment or refeeding, respectively. Injection of ACT D, an inhibitor of gene transcription, decreased insulin receptor mRNA levels by > or = 80% in control and diabetic rats and suppressed the overexpression of mRNA seen in diabetic rats. In vitro nuclear transcription assays showed that the rate of transcription of the insulin receptor gene was increased 2-fold in STZ-induced diabetic rats and fasted rats relative to control animals. Taken together, these results suggest that the upregulation of the insulin receptor induced by chronic insulinopenia results, at least in part, from an increase in insulin receptor gene transcription.

show abstract

“…The insulin receptor promoter has many similarities to the SV40 promoter. Both are bidirectional promoters with multiple transcriptional start sites (5,10,24). Both promoters contain multiple elements that bind Spl (10,25).…”

Section: Discussionmentioning

confidence: 99%

Proximal Enhancer of the Human Insulin Receptor Gene Binds the Transcription Factor Sp1

et al. 1994

View full text Add to dashboard Cite

The insulin receptor is a growth regulator present on the surface of most cells that transmits a mitogenic signal in response to insulin. Thus, the gene for the insulin receptor is constitutively expressed at low levels in all cells. We characterize a constitutive enhancer element that is present in the proximal promoter of the human insulin receptor gene. We have localized the enhancer to a 26-base-pair (26-bp) sequence from -528 to -503. When this sequence is inserted into the proximal promoter, a three- to fourfold increase in promoter activity is observed, and when two copies are inserted, a five- to sixfold increase is seen. Electrophoretic mobility shift analysis demonstrates that nuclear factors binding to this sequence are found in many different cell types. At least two proteins with different specificities bind within this 26-bp sequence. The identity of the predominant binding protein is Sp1, because an oligonucleotide composed of an Sp1 consensus binding sequence can compete for several of the DNA-protein complexes. In addition, we demonstrate that purified Sp1 can bind to the 26-bp oligonucleotide and that this complex comigrates with a DNA-protein complex formed with a HeLa nuclear extract. Finally, an antibody to human Sp1 protein is able to bind to the enhancer DNA/HeLa protein complex and supershift this complex. These findings suggest that this sequence corresponds to a general element that may contribute to the ubiquitous expression of the human insulin receptor gene.

show abstract

Effects of Media Conditions, Insulin, and Dexamethasone on Insulin-Receptor mRNA and Promoter Activity in HepG2 Cells

Cited by 16 publications

References 20 publications

Changes in insulin-receptor mRNA levels in skeletal muscle and brown adipose tissue of weanling rats during fasting and refeeding

Changes in insulin-receptor mRNA levels in skeletal muscle and brown adipose tissue of weanling rats during fasting and refeeding

Effects of STZ-Induced Diabetes and Fasting on Insulin Receptor mRNA Expression and Insulin Receptor Gene Transcription in Rat Liver

Proximal Enhancer of the Human Insulin Receptor Gene Binds the Transcription Factor Sp1

Contact Info

Product

Resources

About