Objectives:

Reported here are the effects of a high-fat diet (HFD) fed to dams during pregnancy on the weight, β-and α-cell development, and β-cell function of their weanling offspring.

Methods:

Offspring were obtained from dams maintained on an HFD for the first, second, or third week of gestation or throughout gestation and then on a standard laboratory diet for the duration of lactation. Weanling weights and circulating glucose and insulin concentrations were measured on postnatal day 21, after which pancreata were excised and snap-frozen for quantitative polymerase chain reaction of glucokinase (GK) or processed for immunohistochemical examination and image analysis (β-and α-cell volume, number, and size, and GK immunoreactivity).

Results:

All of the weanlings had low body weights and were hypoinsulinemic. In weanlings maintained on an HFD for either the first, second, or third week of gestation, hyperglycemia and a reduction in β-cell volume and number, in β-and α-cell size, and in both GK messenger RNA expression and immunoreactivity were observed. The development of β and α cells was normal in weanlings maintained on an HFD throughout gestation.

Conclusions:

Maintenance of dams on an HFD for any single week of gestation results in weanling offspring with an impairment in β-cell development and function.