Divergent regulation of rat adipocyte GLUT1 and GLUT4 glucose transporters by GH

Kilgour, Elaine; Baldwin, S. A.; Flint, David

doi:10.1677/joe.0.1450027

Cited by 24 publications

(20 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we found no increase in GLUT4 RNA. Previous reports have concluded that chronic GH treatment of 3T3-F442A adipocytes and rat adipocytes affects the redistribution of GLUT4, with no effect on the level of expression (17,18). A similar mechanism may explain our results.…”

Section: Sensitivity Responsivenesssupporting

confidence: 83%

“…GH also has a lipolytic effect in most species, including man (15) and may induce insulin resistance (16). Chronic exposure to GH in vitro (adipocyte-derived cell line 3T3-F442A) and in vivo (rat adipocytes) decreases the amount of both GLUT1 and GLUT4 present in adipocyte plasma membrane (17,18). Only two studies have been published in which the effect of GH treatment on lipogenesis in isolated human adipocytes was studied.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of growth hormone treatment on insulin action in adipocytes from children with Prader-Willi syndrome

Kamel¹,

Norgren²,

Lindgren

et al. 1998

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: To study the effect of growth hormone (GH) treatment (2-4 months) on insulin action in adipocytes isolated from children with Prader-Willi syndrome (PWS), in whom GH deficiency appears to be a primary defect. We investigated the complex effects of GH on carbohydrate metabolism, as part of a current clinical trial of GH treatment in children with PWS. Methods: Biopsies of subcutaneous abdominal adipose tissue were obtained from 12 children with PWS before and after 2-4 months of GH treatment. Lipogenesis was determined by the incorporation of radiolabelled glucose into lipids in isolated adipocytes, and glycerol release to the incubation medium was used as an index of lipolysis. GLUT4 RNA was measured by solution hybridization. Results: With low glucose concentrations, at which glucose transport is rate-limiting, maximal insulininduced lipogenesis was increased by 120% after GH treatment (P < 0.05), but the sensitivity to insulin (half-maximum effective hormone concentration) was unchanged. This was not accompanied by a significant change in the RNA expression of GLUT4. Neither responsiveness (maximum effect) nor sensitivity of insulin-induced inhibition of lipolysis was affected by GH treatment. Conclusions: GH treatment of children with PWS results in an upregulation of insulin-induced lipogenesis in isolated adipocytes, with no effect on insulin-induced inhibition of lipolysis. The data suggest that the site of the effect of GH on lipogenesis is distal to the insulin hormone-receptor interaction, but does not involve altered GLUT4 expression.

show abstract

Section: Sensitivity Responsivenesssupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Effect of growth hormone treatment on insulin action in adipocytes from children with Prader-Willi syndrome

Kamel¹,

Norgren²,

Lindgren

et al. 1998

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…toward GH-induced perturbations in insulin-responsive glucose transport cannot be excluded (59). Our results indicate that GHR increases in the adult as compared with the neonatal heart and that GH can increase the fatty acid uptake by cardiomyocytes expressing GHR.…”

Section: Gh Stimulates Hypertrophy Of Isolated Cardiomyocytes-mentioning

confidence: 63%

Demonstration of Direct Effects of Growth Hormone on Neonatal Cardiomyocytes

Lü

Schwartzbauer

Sperling

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

The cellular and molecular basis of growth hormone (GH) actions on the heart remain poorly defined, and it is unclear whether GH effects on the myocardium are direct or mediated at least in part via insulin-like growth factor (IGF-1). Here, we demonstrate that the cultured neonatal cardiomyocyte is not an appropriate model to study the effects of GH because of artifactual loss of GH receptors (GHRs). To circumvent this problem, rat neonatal cardiomyocytes were infected with a recombinant adenovirus expressing the murine GHR. Functional integrity of GHR was suggested by GH-induced activation of the cognate JAK2/STAT5, MAPK, and Akt intracellular pathways in the cells expressing GHR. Although exposure to GH resulted in a significant increase in the size of the cardiomyocyte and increased expression of c-fos, myosin light chain 2, and skeletal ␣-actin mRNAs, there were no significant changes in IGF-1 or atrial natriuretic factor mRNA levels in response to GH stimulation. In this model, GH increased incorporation of leucine, uptake of palmitic acid, and abundance of fatty acid transport protein mRNA. In contrast, GH decreased uptake of 2-deoxy-D-glucose and levels of Glut1 protein. Thus, in isolated rat neonatal cardiomyocytes expressing GHR, GH induces hypertrophy and causes alterations in cellular metabolic profile in the absence of demonstrable changes in IGF-1 mRNA, suggesting that these effects may be independent of IGF-1.Several observations implicate a role for growth hormone (GH) 1 in modulation of cardiac structure and function (1). Patients with excess endogenous GH (i.e. acromegaly) suffer from cardiac complications including biventricular hypertrophy, impaired diastolic filling, and decreased cardiac performance on effort due to diastolic and systolic dysfunction (2). Patients with chronic GH deficiency also show cardiac abnormalities; in general, the data support the presence of a hypokinetic cardiac syndrome in patients with GH deficiency that can be reversed with GH replacement therapy (3-5). Fazio et al. (6) reported that GH therapy in patients with idiopathic dilated cardiomyopathy was associated with significant improvement in left ventricular ejection fraction, isovolumic relaxation time, and efficiency of myocardial energy utilization. Subsequent to these landmark findings, some studies have supported a beneficial effect of exogenous GH on cardiac function (7), whereas other investigators were unable to demonstrate salutary effects of GH on cardiac function in patients with heart failure (8).A particularly well studied animal model is that of the transplanted GH-secreting pituitary tumor cell line, GH 3. In this model of GH excess, there is increased myocardial contractility and calcium sensitivity of myocardial contractile proteins (1). Similarly, normal rats given recombinant GH show an increase in left ventricular mass, as well as an increase in several aspects of cardiac performance (9). In the rodent model of myocardial infarction, administration of GH results in improvements in myocardial ...

show abstract

“…Of note, the IGF-I receptor is not expressed in the mature adipocyte [117], and, thus, the effect of systemic GH treatment on adipocyte function is not mediated by IGF-I. GH treatment in vivo [118, 119]or longer exposure of GH in vitro [120, 121, 122, 123, 124]induces a suppression of glucose metabolism in adipose tissues in the presence or absence of insulin. GH acts at multiple sites on insulin-signaling pathways to induce insulin resistance.…”

Section: Effect Of Gh On Adipocytesmentioning

confidence: 99%

Growth Hormone and Adipocyte Function in Obesity

Nam

Marcus

2000

Horm Res Paediatr

View full text Add to dashboard Cite

In obesity, growth hormone (GH) secretion is impaired which is considered a consequence rather than a cause of obesity. GH regulates the expression of GH receptor and the synthesis of insulin-like growth factor I (IGF-I) in adipocytes. Although GH hyposecretion in obesity may decrease the generation of IGF-I in each adipocyte, increased amounts of IGF-I and GH-binding protein could be secreted from the excessively enlarged amounts of adipose tissue. This may contribute to the normal/high serum-IGF-I and high GH-binding protein levels in obesity. Hyperinsulinemia and increased GH receptor activity may also affect the GH-IGF-I axis. Favorable effects of GH treatment have been observed in obese children and adults. GH treatment decreases adiposity, reduces triglyceride accumulation by inhibiting lipoprotein lipase and enhances lipolysis both via increased hormone-sensitive lipase activity and via induction of beta adrenoreceptors. GH treatment also has a favorable effect on obesity-associated dyslipidemia, but the effects on insulin sensitivity have been conflicting.

show abstract

Divergent regulation of rat adipocyte GLUT1 and GLUT4 glucose transporters by GH

Cited by 24 publications

References 21 publications

Effect of growth hormone treatment on insulin action in adipocytes from children with Prader-Willi syndrome

Effect of growth hormone treatment on insulin action in adipocytes from children with Prader-Willi syndrome

Demonstration of Direct Effects of Growth Hormone on Neonatal Cardiomyocytes

Growth Hormone and Adipocyte Function in Obesity

Contact Info

Product

Resources

About