title: Nutritional challenges during development induce sex-specific changes in glucose homeostasis in the adult sheep.
abstract: The early-life environment has implications for risk of adult-onset diseases, such as glucose intolerance, insulin insensitivity, and obesity, effects that may occur with or without reduced birth weight. We determined the consequences of nutrient restriction in early gestation and early postnatal life and their interactions on postnatal growth, body composition, and glucose handling. Ewes received 100% (C, n = 39) or 50% nutritional requirements (U, n = 41) from 1 to 31 days gestation and 100% thereafter. Male and female offspring (singleton/twin) from C and U ewes were then fed either ad libitum (CC n = 22, UC n = 19) or to reduce body weight to 85% of target from 12 to 25 wk of age (CU n = 17, UU n = 22) and ad libitum thereafter. At 1.5 and 2.5 yr, glucose handling was determined by area under the curve (AUC) for glucose and insulin concentrations following intravenous glucose (0.5 g/kg body wt). Insulin sensitivity was determined at 2.5 yr following intravenous insulin (0.5 IU/kg). In females, postnatal undernutrition reduced (P < 0.05) glucose AUC at both ages, regardless of prenatal nutrition. Postnatal undernutrition did not affect insulin secretion in females but enhanced insulin-induced glucose disappearance in singletons. Poor early postnatal growth was associated with increased fat in females. In males, glucose tolerance was unaffected by undernutrition despite changes in insulin AUC dependent on age, treatment, and single/twin birth. Nutrition in early postnatal life has long-lasting, sex-specific effects on glucose handling in sheep, likely due, in females, to enhanced insulin sensitivity. Improved glucose utilization may aid weight recovery but have negative implications for glucose homeostasis and body composition over the longer term.
authors.affiliation: Centre for DOHaD, University of Southampton, Princess Anne Hospital, Level F (MP 887 Coxford Road, Southampton SO16 5YA, UK. kpoore@soton.ac.uk
authors.forename: Kirsten R
authors.initials: KR
authors.lastname: Poore
authors.forename: Jane K
authors.initials: JK
authors.lastname: Cleal
authors.forename: James P
authors.initials: JP
authors.lastname: Newman
authors.forename: Julian P
authors.initials: JP
authors.lastname: Boullin
authors.forename: David E
authors.initials: DE
authors.lastname: Noakes
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hanson
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Green
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006128:Growth; D006706:Homeostasis; D007328:Insulin / Q000032:analysis / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D009751:Nutritional Requirements; D010179:Pancreas / Q000737:chemistry; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D039401:Prenatal Nutritional Physiological Phenomena; D012727:Sex Characteristics; D012756:Sheep
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose