Glucose metabolic adaptations in the intrauterine growth-restricted adult female rat offspring.
We studied glucose metabolic adaptations in the intrauterine growth-restricted (IUGR) rat offspring to decipher glucose homeostasis in metabolic programming. Glucose futile cycling (GFC), which is altered when there is imbalance between glucose production and utilization, was studied during a glucose tolerance test (GTT) in 2-day-old (n = 8), 2-mo-old (n = 22), and 15-mo-old (n = 22) female rat offspring. The IUGR rats exposed to either prenatal (CM/SP, n = 5 per age), postnatal (SM/CP, n = 6), or pre- and postnatal (SM/SP, n = 6) nutrient restriction were compared with age-matched controls (CM/CP, n = 5). At 2 days, IUGR pups (SP) were smaller and glucose intolerant and had increased hepatic glucose production and increased glucose disposal (P < 0.01) compared with controls (CP). At 2 mo, the GTT, glucose clearance, and GFC did not change. However, a decline in hepatic glucose-6-phosphatase (P < 0.05) and fructose-1,6-biphosphatase (P < 0.05) enzyme activities in the IUGR offspring was detected. At 15 mo, prenatal nutrient restriction (CM/SP) resulted in greater weight gain (P < 0.01) and hyperinsulinemia (P < 0.001) compared with postnatal nutrient restriction (SM/CP). A decline in GFC in the face of a normal GTT occurred in both the prenatal (CM/SP, P < 0.01) and postnatal calorie (SM/CP, P < 0.03) and growth-restricted offspring. The IUGR offspring with pre- and postnatal nutrient restriction (SM/SP) were smaller, hypoinsulinemic (P < 0.03), and hypoleptinemic (P < 0.03), with no change in GTT, hepatic glucose production, GFC, or glucose clearance. We conclude that there is pre- and postnatal programming that affects the postnatal compensatory adaptation of GFC and disposal initiated by changes in circulating insulin concentrations, thereby determining hepatic insulin sensitivity in a phenotype-specific manner.
Garg
Meena
M
Division of Neonatology and Developmental Biology, Dept. of Pediatrics, David Geffen School of Medicine, UCLA, 10833 Le Conte, MDCC-B2-375, Los Angeles, CA 90095-1752, USA.
Thamotharan
Manikkavasagar
M
Rogers
Lisa
L
Bassilian
Sara
S
Lee
W N Paul
WN
Devaskar
Sherin U
SU
D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D001835:Body Weight; D031204:Caloric Restriction / Q000009:adverse effects* / Q000379:methods; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006706:Homeostasis; D007774:Lactation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005952:Glucose-6-Phosphatase; D005947:Glucose