Activation of inflammasomes in adipose tissue of women with gestational diabetes.
Gestational diabetes mellitus (GDM) is characterised by maternal peripheral insulin resistance, increased inflammation, and increasing levels of circulating free fatty acids (FFAs) and advanced glycation endproducts (AGEs). Caspase-1 is a key component of the inflammasome, which is activated upon cellular infection or stress to trigger the maturation IL-1β, a pro-inflammatory cytokine that mediated insulin resistance. The aim of this study was to determine whether the inflammasome is activated in adipose tissue from women with gestational diabetes mellitus (GDM) and if it interferes with the insulin signalling pathway leading to the insulin resistance that is evident in GDM. Protein expression of active caspase-1 and mature IL-1β secretion was increased in adipose tissue of women with GDM. Treatment of adipose tissue with IL-1β decreased insulin-stimulated phosphorylation of IRS-1, GLUT-4 expression and glucose uptake. Low-grade inflammation (induced by LPS), the FFA palmitate and AGE conjugated to BSA (AGE-BSA), induced IL-1β secretion via inflammasome activation. In conclusion, the present findings describe an important role for adipose tissue inflammasome activation in the development of insulin resistance associated in pregnancies complicated by GDM.
Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia. Electronic address: mlappas@unimelb.edu.au.
Martha
M
Lappas
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D020170:Caspase 1 / Q000378:metabolism; D016640:Diabetes, Gestational / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D017127:Glycation End Products, Advanced / Q000494:pharmacology; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D010168:Palmitates / Q000494:pharmacology; D011247:Pregnancy; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D017127:Glycation End Products, Advanced; D058847:Inflammasomes; D007328:Insulin; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D010168:Palmitates; D058486:Receptors, Purinergic P2X7; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D000255:Adenosine Triphosphate; D020170:Caspase 1
Adipose tissue; GDM; IL-1β; Inflammasome; Inflammation; Insulin signalling