Endocrine Abstracts (2015) 38 P217 | DOI: 10.1530/endoabs.38.P217

Enhanced insulin secretion and insulin action in young lambs with intrauterine growth restriction

Leticia Camacho & Sean Limesand

University of Arizona, Tucson, Arizona, USA.

Intrauterine growth restriction (IUGR) is associated with postnatal metabolic complications, which include glucose intolerance in adulthood. However, information is limited on the progression of insulin secretion and its action in young IUGR infants. The objective of this study was to determine glucose stimulated insulin secretion and insulin action in young lambs with placenta insufficiency-induced IUGR.

Placental insufficiency-induced IUGR was created by exposing pregnant ewes to high ambient temperatures during mid gestation, and the IUGR lambs (n=5) were compared to lambs (n=8) from pair-fed, thermoneutral ewes. Lambs were reared on milk replacer. At 8±1 days of age, a square-wave hyperglycaemic clamp was performed after 3 h fast to measure glucose stimulated insulin secretion. At 15±1 days insulin sensitivity was determined with a hyperinsulinaemic-euglycemic clamp. Basal and hyperinsulinaemic glucose utilization rates were measured with [14C(U)]-D-glucose.

IUGR lambs had lighter birthweights than control lambs (3.8±0.7 kg vs 4.7±0.9 kg; P=0.04). Fasting plasma glucose and insulin concentrations were not different. During the square-wave hyperglycaemic clamp, insulin secretion for the first 20 min of hyperglycaemia was greater in IUGR lambs than in controls (159±30 vs 68±24 μg×min/l). No differences were found between treatments for second phase insulin secretion or glucose-potentiated arginine stimulated insulin secretion. Fasting and hyperinsulinaemic glucose utilization rates were not different between treatments, but IUGR lambs had greater insulin sensitivity compared to control lambs in both periods (basal 5.36±1.00 vs 3.23±0.36 μmol×l/mU per min per kg; hyperinsulinaemic 2.04±0.64 vs 0.85±0.08 μmol×l/mU per min per kg). Insulin disposition index, the product of insulin sensitivity and acute insulin secretion, was increased 4.7 fold at basal and 6.5 fold with hyperinsulinemia in IUGR lambs.

A greater insulin disposition index demonstrates that young IUGR lambs have inappropriate insulin secretion for their insulin sensitivity. This imbalance between secretion and sensitivity of insulin may promote a loss of function that results in glucose intolerance.

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