The effects of aging on glucose metabolism in adipocytes from Fischer rats.
We have studied glucose metabolism in adipocytes from younger (6 months) and older (24 months) Fischer rats. Insulin binding was similar in both groups, expressed per cell number (2.67 +/- 0.41% vs. 2.96 +/- 0.38%) or per cell surface area (4.59 +/- 0.70% vs. 4.15 +/- 0.53%) in the 6- and 24-month-old animals, respectively. Maximal insulin-stimulated 3-O-methylglucose transport was decreased by 40% in the older group (0.234 +/- 0.032) compared with that in the younger group (0.411 +/- 0.031 pmol/2 X 10(9) micron 2 X sec (P less than 0.01), with no change in basal rates of transport. The decrease in glucose transport was due to a 36% reduction in the maximum velocity (91 pmol/sec in the younger vs. 59 pmol/sec in the older group), with no change in the Km. Postglucose transport steps of glucose metabolism, including CO2 oxidation, triglyceride synthesis, and lactate production, were measured at a higher glucose concentration (2 mM), where glucose transport is not rate limiting. Overall maximal insulin-stimulated glucose metabolism was decreased by 45% in the older group (15.6 nmol) compared with that in the younger group (28.6 nmol/10(5) cells X h; P less than 0.05). Glucose oxidation was decreased by 42% (2.9 vs. 5.0 nmol/10(5) cells X h; P less than 0.05), triglyceride synthesis by 40% (5.9 vs. 9.8 nmol/10(5) cells X h; P less than 0.05), and lactate production by 47% (6.3 vs. 11.8 nmol/10(5) cells X h; P less than 0.05). We conclude that in adipocytes from aged Fischer rats, cellular insulin resistance is due to multiple post-binding defects involving the glucose transport system and more distal intracellular processes.
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000375:Aging; D000818:Animals; D001692:Biological Transport; D002952:Citric Acid Cycle; D005215:Fasting; D005947:Glucose / Q000378:metabolism*; D006600:Hexosephosphates / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007773:Lactates / Q000378:metabolism; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis
D006600:Hexosephosphates; D007328:Insulin; D007773:Lactates; D008757:Methylglucosides; D014280:Triglycerides; D011972:Receptor, Insulin; D005947:Glucose