Poor fetal nutrition causes long-term changes in expression of insulin signaling components in adipocytes.
Insulin action on adipocytes was studied in the offspring of mothers who had been fed either a control (20% protein) or a low (8%)-protein diet during pregnancy and lactation. Adipocytes isolated from low-protein offspring had significantly higher basal and insulin-stimulated glucose uptakes than controls. This may be related to a threefold increase in insulin receptors in low-protein adipocytes. Consistent with these observed changes in glucose transport, adipocytes from low-protein animals had significantly higher basal and insulin-stimulated insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activities. There was also more p85-associated PI 3-kinase activity in these adipocytes. There was no difference in expression in the p85 regulatory subunit or the p110-alpha catalytic subunit of PI 3-kinase. In contrast, there was a sixfold reduction in the p110-beta catalytic subunit of PI 3-kinase in adipocytes from low-protein animals. These results suggest that poor fetal nutrition during pregnancy and lactation can have long-term effects on glucose transport and on the expression of key components of the insulin signaling pathway in adipocytes.
Ozanne
S E
SE
Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, United Kingdom.
Nave
B T
BT
Wang
C L
CL
Shepherd
P R
PR
Prins
J
J
Smith
G D
GD
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001835:Body Weight; D002478:Cells, Cultured; D004822:Epididymis; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D007774:Lactation; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009929:Organ Size; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D011297:Prenatal Exposure Delayed Effects; D011502:Protein-Energy Malnutrition / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D009004:Monosaccharide Transport Proteins; D010750:Phosphoproteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D005947:Glucose