Expression of glucose transporter 4 mrna in adipose tissue- and skeletal muscle of ovariectomized rats treated with sex steroid hormones

Sugaya, Ayumi; Sugiyama, Takashi; Yanase, Sachiko; Shen, Xiaoxiong; Minoura, Hiroyuki; Toyoda, Nagayasu

doi:10.1016/s0024-3205(99)00636-0

Cited by 37 publications

(27 citation statements)

References 29 publications

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“…6). These results are consistent with previous reports that the expression of GLUT4 was unchanged in the adipose tissue of ovariectomized rats with progesterone administration (36) and that insulin-induced GLUT4 translocation was impaired in omental adipocytes from patients with GDM (8).…”

Section: Discussionsupporting

confidence: 93%

Progesterone inhibits glucose uptake by affecting diverse steps of insulin signaling in 3T3-L1 adipocytes

Wada¹,

Hori²,

Sugiyama³

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Maternal insulin resistance is essential for efficient provision of glucose to the fetus. Although elevation of placental hormones is known to relate to the development of insulin resistance, the precise underlying mechanism of maternal insulin resistance is unknown. Therefore, we examined the molecular mechanisms of progesterone causing insulin resistance in 3T3-L1 adipocytes. Progesterone at 10 Ϫ4 M, but not 10 Ϫ5 M, reduced the amount of IRS-1. As a result, insulin-induced phosphorylation of IRS-1, the association of IRS-1 with p85␣, and subsequent phosphorylation of Akt1 and -2 was decreased moderately by 10 Ϫ4 M progesterone. Subsequently, insulin-induced translocation of GLUT4 to the plasma membrane evaluated by immunostaining on the plasma membrane sheet by confocal laser microscope was also decreased by 10 Ϫ4 M progesterone. In contrast, 2-[ 3 H]deoxyglucose (2DG) uptake was markedly inhibited by both 10 Ϫ5 and 10 Ϫ4 M progesterone in a dose-dependent manner. Surprisingly, 2DG uptake elicited by adenovirus-mediated expression of constitutive-active mutant of PI 3-kinase (myr-p110) and Akt (myr-Akt) was suppressed by progesterone. Interestingly, insulin-induced tyrosine phosphorylation of Cbl and activation of TC10 were inhibited by progesterone at 10 Ϫ5 M. These results indicate that progesterone is implicated in insulin resistance during pregnancy by inhibiting the PI 3-kinase pathway at the step of 1) IRS-1 expression and 2) distal to Akt and 3) by suppressing the PI 3-kinase-independent pathway of TC10 activation by affecting Cbl phosphorylation. gestational diabetes; insulin resistance; TC10

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Section: Discussionsupporting

confidence: 93%

Progesterone inhibits glucose uptake by affecting diverse steps of insulin signaling in 3T3-L1 adipocytes

Wada¹,

Hori²,

Sugiyama³

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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“…In the pregnancy scenario, the diabetogenic effect of progesterone has been mostly explained by the enhancement of insulin resistance (Butte 2000), particularly in skeletal muscle and adipose tissue, through a reduction in glucose transporter 4 (GLUT4 (SLC2A4)) expression (Sugaya et al 2000). However, considering that apoptosis is involved in the pathophysiology of type 1 and 2 diabetes and also contributes to the involution of the b-cell mass in the postpartum phase (Scaglia et al 1995), we first proposed the hypothesis that progesterone might be involved in b-cell death, also contribute to the development of gestational diabetes (GD).…”

Section: Introductionmentioning

confidence: 99%

Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism

Nunes¹,

Portioli-Sanches²,

Rosim³

et al. 2014

Journal of Endocrinology

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Progesterone has been associated with the development of gestational diabetes (GD) due to the enhancement of insulin resistance. As b-cell apoptosis participates in type 1 and type 2 diabetes pathophysiology, we proposed the hypothesis that progesterone might contribute to the development of GD through a mechanism that also involves b-cell death. To address this question, RINm5F insulin-producing cells were incubated with progesterone (25-100 mM), in the presence or absence of a-tocopherol (40 mM). After 24 or 48 h, membrane integrity and DNA fragmentation were analyzed by flow cytometry. Caspase activity was used to identify the mode of cell death. The involvement of endoplasmic reticulum stress in the action of progesterone was investigated by western blotting. Oxidative stress was measured by 2',7'-dichlorofluorescein diacetate (DCFDA) oxidation. Isolated rat islets were used in similar experiments in order to confirm the effect of progesterone in primary b-cells. Incubation of RINm5F cells with progesterone increased the number of cells with loss of membrane integrity and DNA fragmentation. Progesterone induced generation of reactive species. Pre-incubation with a-tocopherol attenuated progesterone-induced apoptosis. Western blot analyses revealed increased expression of CREB2 and CHOP in progesteronetreated cells. Progesterone caused apoptotic death of rat islet cells and enhanced generation of reactive species. Our results show that progesterone can be toxic to pancreatic b-cells through an oxidative-stress-dependent mechanism that induces apoptosis. This effect may contribute to the development of GD during pregnancy, particularly under conditions that require administration of pharmacological doses of this hormone.

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“…This difference indicated the existence of tissue-specific regulation. The phenomenon has been observed in many different models of diabetes, obesity and insulin resistance [30,31].…”

Section: Discussionmentioning

confidence: 95%

Effect of iron supplementation on glucose transporter 4 expression in adipose tissue and skeletal muscle of pregnant rats

He¹,

Jiang²,

Liu³

et al. 2013

OJOG

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Objective: The main goal of the present study was to investigate the effect of iron supplementation on glucose transporter 4 expressions in adipose tissue and skeletal muscle in female rats during pregnancy. Methods: Twenty-four pregnant Sprague-Dawley rats were randomly divided into 2 groups: a control group with a standard diet (containing iron 150 mg/kg) and an iron-supplementation group with a high-iron diet (containing iron 700 mg/kg) from day 0 to day 21 of pregnancy. Intraperitoneal glucose tolerance test was performed on gestational day 19. On gestational day 21, all of the pregnant rats from each group were sacrificed. The mean neonatal weights were measured and samples of maternal intraabdominal adipose tissue and skeletal muscle were taken to measure the expression of Glucose Transporter 4 (GLUT4) mRNA and protein. Results: Glucose tolerance decreased significantly in the iron supplementation group compared to the control group. The mean neonatal weights in the iron supplementation group were higher than that in the control group. Levels of GLUT4 mRNA in the adipose tissue were reduced by the administrations of high-iron diet. The skeletal muscle GLUT4 mRNA levels were not changed significantly by iron supplementation. Expression of GLUT4 protein both in the adipose tissue and skeletal muscle reduced significantly. Conclusion: These results suggest that iron supplementation during pregnancy would increase neonatal weights and could decrease maternal glucose tolerance by interfering GLUT4 expression in adipose tissue and skeletal muscle of rats.

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Expression of glucose transporter 4 mrna in adipose tissue- and skeletal muscle of ovariectomized rats treated with sex steroid hormones

Cited by 37 publications

References 29 publications

Progesterone inhibits glucose uptake by affecting diverse steps of insulin signaling in 3T3-L1 adipocytes

Progesterone inhibits glucose uptake by affecting diverse steps of insulin signaling in 3T3-L1 adipocytes

Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism

Effect of iron supplementation on glucose transporter 4 expression in adipose tissue and skeletal muscle of pregnant rats

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