Insulin secretion rates are greater after oral
glucose than after parenteral administration of an equivalent
glucose load. This augmented beta-cell secretory response to an oral
glucose load results from the release of mainly two gut
hormones:
gastric inhibitory polypeptide (GIP) and
glucagon-like peptide-1, which potentiate
glucose-induced insulin secretion. Because of their insulinotropic action, their abnormal secretion may be involved in the pathogenesis of the
hyperinsulinemia of
childhood obesity. In this study, we used the hyperglycemic clamp with a small oral
glucose load to assess the effect of
childhood obesity on GIP response in seven prepubertal lean and 11 prepubertal obese children and in 14 lean adolescents and 10 obese adolescents. Plasma
glucose was acutely raised to 11 mM by infusing i.v.
glucose and kept at this concentration for 180 min. Each subject ingested oral
glucose (30 g) at 120 min, and the
glucose infusion was adjusted to maintain the plasma
glucose plateau. Basal
insulin and
C-peptide concentrations and insulin secretion rates (calculated by the deconvolution method) were significantly greater in obese children compared with lean children (p < 0.001). Similarly, during the first 120 min of the clamp, insulin secretion rates were higher in obese than lean children. After oral
glucose, plasma
insulin,
C-peptide, and insulin secretion rates further increased in all four groups. This
incretin effect was 2-fold greater in obese versus lean adolescents (p < 0.001). Circulating plasma GIP concentrations were similar at baseline in all four groups and remained unchanged during the first 120 min of the clamp. After oral
glucose, plasma GIP concentrations rose sharply in all groups (p < 0.002). Of note, the rise in GIP was similar in both lean and obese children. In conclusion, under conditions of stable
hyperglycemia, the ingestion of a small amount of
glucose elicited equivalent GIP responses in both lean and obese children. However, despite similar GIP responses, insulin secretion was markedly augmented in obese adolescents. Thus, in juvenile
obesity, excessive alimentary beta-cell stimulation may be independent of the increased release of GIP.