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Insulin differentially modulates the peripheral endocannabinoid system in human subcutaneous abdominal adipose tissue from lean and obese individuals.

Murdolo, Giuseppe, 1966 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
Kempf, K (författare)
Hammarstedt, Ann, 1975 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Herder, C. (författare)
Smith, Ulf, 1943 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
Jansson, Per-Anders, 1961 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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 (creator_code:org_t)
2007
2007
Engelska.
Ingår i: Journal of endocrinological investigation. - 1720-8386. ; 30:8
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Human obesity has been associated with a dysregulation of the peripheral and adipose tissue (AT) endocannabinoid system (ES). The aim of this study was to elucidate the acute in vivo effects of insulin on gene expression of the cannabinoid type 1 (CB-1) and type 2 (CB-2) receptors, as well as of the fatty acid amide hydrolase (FAAH) in the sc abdominal adipose tissue (SCAAT). Nine lean (L) and 9 obese (OB), but otherwise healthy males were studied in the fasting state and during a euglycemic hyperinsulinemic clamp (40 mU/m2 * min(-1)). SCAAT biopsies were obtained at baseline and after 270 min of i.v. maintained hyperinsulinemia. The basal SCAAT gene expression pattern revealed an upregulation of the FAAH in the OB (p=0.03 vs L), whereas similar CB-1 and CB-2 mRNA levels were seen. Following hyperinsulinemia, the FAAH mRNA levels significantly increased approximately 2-fold in the L (p=0.01 vs baseline) but not in the OB. In contrast, insulin failed to significantly change both the adipose CB-1 and CB-2 gene expression. Finally, the FAAH gene expression positively correlated with the fasting serum insulin concentration (r 0.66; p=0.01), whereas an inverse association with the whole-body glucose disposal (r -0.58; p<0.05) was seen. Taken together, these first time observations demonstrate that the ES-related genes in the SCAAT differentially respond to hyperinsulinemia in lean/insulin-sensitive and in obese/insulin-resistant individuals. We suggest that insulin may play a key role in the obesity-linked dysregulation of the adipose ES at the gene level.

Nyckelord

Adult
Biopsy
Body Weight
Diabetes Mellitus
Type 2
drug therapy
metabolism
Fasting
physiology
Gene Expression
drug effects
physiology
Humans
Hyperinsulinism
metabolism
Hypoglycemic Agents
administration & dosage
blood
Insulin
administration & dosage
blood
Male
Obesity
metabolism
Receptor
Cannabinoid
CB1
genetics
Receptor
Cannabinoid
CB2
genetics
Subcutaneous Fat
Abdominal
cytology
drug effects
physiology
Up-Regulation
drug effects
physiology

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