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Evidence that oestr...
Evidence that oestrogen receptor-alpha plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver
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- Bryzgalova, G (author)
- Karolinska Institutet
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- Gao, H (author)
- Karolinska Institutet
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- Ahrén, Bo (author)
- Lund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Zierath, JR (author)
- Karolinska Institutet
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- Galuska, D (author)
- Karolinska Institutet
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Steiler, TL (author)
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- Dahlman-Wright, K (author)
- Karolinska Institutet
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Nilsson, S (author)
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- Gustafsson, JA (author)
- Karolinska Institutet
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Efendic, S (author)
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Khan, A (author)
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(creator_code:org_t)
- 2006-02-04
- 2006
- English.
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In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 49:3, s. 588-597
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Abstract
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- Aims/hypothesis: We used oestrogen receptor-alpha (ER alpha) knockout (ERKO) and receptor-beta (ER beta) knockout (BERKO) mice to investigate the mechanism(s) behind the effects of oestrogens on glucose homeostasis. Methods: Endogenous glucose production (EGP) was measured in ERKO mice using a euglycaemic-hyperinsulinaemic clamp. Insulin secretion was determined from isolated islets. In isolated muscles, glucose uptake was assayed by using radiolabelled isotopes. Genome-wide expression profiles were analysed by high-density oligonucleotide microarray assay, and the expression of the genes encoding steroyl-CoA desaturase and the Leptin receptor (Scd1 and Lepr, respectively) was confirmed by RT-PCR. Results: ERKO mice had higher fasting blood glucose, plasma insulin levels and IGT. The plasma leptin level was increased, while the adiponectin concentration was decreased in ERKO mice. Levels of both glucose- and arginine-induced insulin secretion from isolated islets were similar in ERKO and wild-type mice. The euglycaemic-hyperinsulinaemic clamp revealed that suppression of EGP by increased insulin levels was blunted in ERKO mice, which suggests a pronounced hepatic insulin resistance. Microarray analysis revealed that in ERKO mice, the genes involved in hepatic lipid biosynthesis were upregulated, while genes involved in lipid transport were downregulated. Notably, hepatic Lepr expression was decreased in ERKO mice. In vitro studies showed a modest decrease in insulin-mediated glucose uptake in soleus and extensor digitorum longus (EDL) muscles of ERKO mice. BERKO mice demonstrated normal glucose tolerance and insulin release. Conclusions/interpretation: We conclude that oestrogens, acting via ER alpha, regulate glucose homeostasis mainly by modulating hepatic insulin sensitivity, which can be due to the upregulation of lipogenic genes via the suppression of Lepr expression.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- stearoyl-CoA desaturase 1
- receptor
- leptin
- insulin resistance
- estrogen receptors
- glucose homeostasis
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Bryzgalova, G
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Gao, H
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Ahrén, Bo
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Zierath, JR
-
Galuska, D
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Steiler, TL
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show more...
-
Dahlman-Wright, ...
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Nilsson, S
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Gustafsson, JA
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Efendic, S
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Khan, A
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Diabetologia
- By the university
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Lund University
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Karolinska Institutet