Improved lactational nutrition and postnatal growth ameliorates impairment of glucose tolerance by uteroplacental insufficiency in male rat offspring.
Intrauterine growth restriction and accelerated postnatal growth predict increased risk of diabetes. Uteroplacental insufficiency in the rat restricts fetal growth but also impairs mammary development and postnatal growth. We used cross fostering to compare the influence of prenatal and postnatal nutritional restraint on adult glucose tolerance, insulin secretion, insulin sensitivity, and hypothalamic neuropeptide Y content in Wistar Kyoto rats at 6 months of age. Bilateral uterine vessel ligation (restricted) to induce uteroplacental insufficiency or sham surgery (control) was performed on d-18 gestation. Control, restricted, and reduced (reducing litter size of controls to match restricted) pups were cross fostered onto a control or restricted mother 1 d after birth. Restricted pups were born small compared with controls. Restricted males, but not females, remained lighter up to 6 months, regardless of postnatal environment. By 10 wk, restricted-on-restricted males ate more than controls. At 6 months restricted-on-restricted males had increased hypothalamic neuropeptide Y content compared with other groups, and together with reduced-on-restricted males had increased retroperitoneal fat weight (percent body weight) compared with control-on-controls. Restricted-on-restricted males had impaired glucose tolerance, reduced first-phase insulin secretion, but unaltered insulin sensitivity, compared with control-on-controls. In males, being born small and exposed to an impaired lactational environment adversely affects adult glucose tolerance and first-phase insulin secretion, but improving lactation partially ameliorates this condition. This study identifies early life as a target for intervention to prevent later diabetes after prenatal restraint.
Siebel
Andrew L
AL
Department of Physiology, University of Melbourne, Parkville, 3010, Australia. asiebel@unimelb.edu.au
Mibus
Amy
A
De Blasio
Miles J
MJ
Westcott
Kerryn T
KT
Morris
Margaret J
MJ
Prior
Larissa
L
Owens
Julie A
JA
Wlodek
Mary E
ME
D000818:Animals; D002149:Energy Intake; D005260:Female; D018149:Glucose Intolerance / Q000517:prevention & control*; D006128:Growth / Q000502:physiology*; D007774:Lactation / Q000502:physiology*; D008297:Male; D021041:Placental Circulation / Q000502:physiology*; D010927:Placental Insufficiency / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D012727:Sex Characteristics; D014599:Uterus / Q000503:physiopathology*