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Role of cannabinoid...
Role of cannabinoid receptor 1 in human adipose tissue for lipolysis regulation and insulin resistance
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- Sidibeh, Cherno O. (author)
- Uppsala universitet,Klinisk diabetologi och metabolism
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- Pereira, Maria J., 1981- (author)
- Uppsala universitet,Klinisk diabetologi och metabolism
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- Börjesson, Joey Lau, 1979- (author)
- Uppsala universitet,Klinisk diabetologi och metabolism
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- Kamble, Prasad G. (author)
- Uppsala universitet,Klinisk diabetologi och metabolism
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- Skrtic, Stanko, 1970 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine,AstraZeneca R&D, Molndal, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Endocrinol, Gothenburg, Sweden.
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- Katsogiannos, Petros (author)
- Uppsala universitet,Klinisk diabetologi och metabolism
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- Sundbom, Magnus (author)
- Uppsala universitet,Gastrointestinalkirurgi
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- Svensson, Maria K. (author)
- Uppsala universitet,Klinisk diabetologi och metabolism
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- Eriksson, Jan W. (author)
- Uppsala universitet,Klinisk diabetologi och metabolism
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(creator_code:org_t)
- 2016-11-17
- 2017
- English.
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In: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 55:3, s. 839-852
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https://uu.diva-port... (primary) (Raw object)
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Abstract
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- We recently showed that the peripheral cannabinoid receptor type 1 (CNR1) gene is upregulated by the synthetic glucocorticoid dexamethasone. CNR1 is highly expressed in the central nervous system and has been a drug target for the treatment of obesity. Here we explore the role of peripheral CNR1 in states of insulin resistance in human adipose tissue. Subcutaneous adipose tissue was obtained from well-controlled type 2 diabetes subjects and controls. Subcutaneous adipose tissue gene expression levels of CNR1 and endocannabinoid synthesizing and degrading enzymes were assessed. Furthermore, paired human subcutaneous adipose tissue and omental adipose tissue from non-diabetic volunteers undergoing kidney donation or bariatric surgery, was incubated with or without dexamethasone. Subcutaneous adipose tissue obtained from volunteers through needle biopsy was incubated with or without dexamethasone and in the presence or absence of the CNR1-specific antagonist AM281. CNR1 gene and protein expression, lipolysis and glucose uptake were evaluated. Subcutaneous adipose tissue CNR1 gene expression levels were 2-fold elevated in type 2 diabetes subjects compared with control subjects. Additionally, gene expression levels of CNR1 and endocannabinoid-regulating enzymes from both groups correlated with markers of insulin resistance. Dexamethasone increased CNR1 expression dose-dependently in subcutaneous adipose tissue and omental adipose tissue by up to 25-fold. Dexamethasone pre-treatment of subcutaneous adipose tissue increased lipolysis rate and reduced glucose uptake. Co-incubation with the CNR1 antagonist AM281 prevented the stimulatory effect on lipolysis, but had no effect on glucose uptake. CNR1 is upregulated in states of type 2 diabetes and insulin resistance. Furthermore, CNR1 is involved in glucocorticoid-regulated lipolysis. Peripheral CNR1 could be an interesting drug target in type 2 diabetes and dyslipidemia.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Type 2 diabetes
- Glucocorticoids
- Insulin resistance
- Adipose tissue
- Endocannabinoid system
- peripheral endocannabinoid system
- glucose-uptake
- human adipocytes
- phosphatidylinositol 3-kinase
- gene-expression
- rat adipocytes
- glucocorticoids
- cb1
- obesity
- kinase
- Endocrinology & Metabolism
- Type 2 diabetes
Publication and Content Type
- ref (subject category)
- art (subject category)
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Endocrine
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Sidibeh, Cherno ...
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Pereira, Maria J ...
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Börjesson, Joey ...
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Kamble, Prasad G ...
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Skrtic, Stanko, ...
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Katsogiannos, Pe ...
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Sundbom, Magnus
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Svensson, Maria ...
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Eriksson, Jan W.
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- MEDICAL AND HEALTH SCIENCES
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Endocrine
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University of Gothenburg
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Uppsala University