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FältnamnIndikatorerMetadata
00005306naa a2200637 4500
001oai:gup.ub.gu.se/253313
003SwePub
008240528s2017 | |||||||||||000 ||eng|
009oai:DiVA.org:uu-320351
0247 a https://gup.ub.gu.se/publication/2533132 URI
0247 a https://doi.org/10.1007/s12020-016-1172-62 DOI
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3203512 URI
040 a (SwePub)gud (SwePub)uu
041 a eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Sidibeh, Cherno O.u Uppsala universitet,Klinisk diabetologi och metabolism4 aut0 (Swepub:uu)chesi291
2451 0a Role of cannabinoid receptor 1 in human adipose tissue for lipolysis regulation and insulin resistance
264 c 2016-11-17
264 1b Springer Science and Business Media LLC,c 2017
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng
653 a Type 2 diabetes
653 a Glucocorticoids
653 a Insulin resistance
653 a Adipose tissue
653 a Endocannabinoid system
653 a peripheral endocannabinoid system
653 a glucose-uptake
653 a human adipocytes
653 a phosphatidylinositol 3-kinase
653 a gene-expression
653 a rat adipocytes
653 a glucocorticoids
653 a cb1
653 a obesity
653 a kinase
653 a Endocrinology & Metabolism
653 a Type 2 diabetes
7001 a Pereira, Maria J.,d 1981-u Uppsala universitet,Klinisk diabetologi och metabolism4 aut0 (Swepub:uu)marpe927
7001 a Börjesson, Joey Lau,d 1979-u Uppsala universitet,Klinisk diabetologi och metabolism4 aut0 (Swepub:uu)jolau226
7001 a Kamble, Prasad G.u Uppsala universitet,Klinisk diabetologi och metabolism4 aut0 (Swepub:uu)kampr247
7001 a Skrtic, Stanko,d 1970u 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.4 aut0 (Swepub:gu)xskrst
7001 a Katsogiannos, Petrosu Uppsala universitet,Klinisk diabetologi och metabolism4 aut0 (Swepub:uu)petka500
7001 a Sundbom, Magnusu Uppsala universitet,Gastrointestinalkirurgi4 aut0 (Swepub:uu)magsundb
7001 a Svensson, Maria K.u Uppsala universitet,Klinisk diabetologi och metabolism4 aut0 (Swepub:uu)marsv604
7001 a Eriksson, Jan W.u Uppsala universitet,Klinisk diabetologi och metabolism4 aut0 (Swepub:uu)janer909
7102 a Uppsala universitetb Klinisk diabetologi och metabolism4 org
7730 t Endocrined : Springer Science and Business Media LLCg 55:3, s. 839-852q 55:3<839-852x 1355-008Xx 1559-0100
8564 u https://link.springer.com/content/pdf/10.1007%2Fs12020-016-1172-6.pdf
8564 u https://uu.diva-portal.org/smash/get/diva2:1089291/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 8u https://gup.ub.gu.se/publication/253313
8564 8u https://doi.org/10.1007/s12020-016-1172-6
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-320351

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