Impaired PI 3-kinase activation in adipocytes from early growth-restricted male rats.
Epidemiological studies have established a relationship between early growth restriction and subsequent development of type 2 diabetes. Animal studies have shown that offspring of protein-restricted rats undergo a greater age-related loss of glucose tolerance than controls. The aim of this study was to investigate the possibility that this deterioration of glucose tolerance is associated with changes in adipocyte insulin action. Adipocytes from low-protein offspring had higher basal levels of glucose uptake than controls. Insulin stimulated glucose uptake into control adipocytes but had little effect on low-protein adipocytes. Both groups had similar levels of basal and isoproterenol-stimulated lipolysis. Insulin inhibited lipolysis in control adipocytes but had a reduced effect on low-protein adipocytes. These changes in insulin action were not related to altered expression of insulin receptors or insulin receptor tyrosine phosphorylation; however, they were associated with reduced phosphatidylinositol 3-kinase and protein kinase B activation. These results demonstrate that reduced glucose tolerance observed in late adult life after early growth restriction is associated with adipocyte insulin resistance.
Ozanne
S E
SE
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QR, UK. seo10@cam.ac.uk
Dorling
M W
MW
Wang
C L
CL
Nave
B T
BT
D017667:Adipocytes / Q000201:enzymology*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D004789:Enzyme Activation; D005260:Female; D005317:Fetal Growth Retardation / Q000201:enzymology*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology; D008066:Lipolysis; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D009124:Muscle Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects; D011488:Protein Deficiency / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000032:analysis
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D019000:Phosphotyrosine; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D005947:Glucose