Augmentation of alimentary insulin secretion despite similar gastric inhibitory peptide (GIP) responses in juvenile obesity

Rubina A. Heptulla, William V. Tamborlane, Melissa Cavaghan, Mary Bronson, Charles Limb, Yong Zhan Ma, Robert S. Sherwin, Sonia Caprio

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Insulin secretion rates are greater after oral glucose than after parenteral administration of an equivalent glucose load. This augmented β- 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 β-cell stimulation may be independent of the increased release of GIP.

Original languageEnglish (US)
Pages (from-to)628-633
Number of pages6
JournalPediatric Research
Volume47
Issue number5
StatePublished - May 2000
Externally publishedYes

Fingerprint

Stomach
Obesity
Insulin
Glucose
Peptides
C-Peptide
Pediatric Obesity
Gastric Inhibitory Polypeptide
Incretins
Glucagon-Like Peptide 1
Hyperinsulinism
Hyperglycemia
Eating
Hormones

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Heptulla, R. A., Tamborlane, W. V., Cavaghan, M., Bronson, M., Limb, C., Ma, Y. Z., ... Caprio, S. (2000). Augmentation of alimentary insulin secretion despite similar gastric inhibitory peptide (GIP) responses in juvenile obesity. Pediatric Research, 47(5), 628-633.

Augmentation of alimentary insulin secretion despite similar gastric inhibitory peptide (GIP) responses in juvenile obesity. / Heptulla, Rubina A.; Tamborlane, William V.; Cavaghan, Melissa; Bronson, Mary; Limb, Charles; Ma, Yong Zhan; Sherwin, Robert S.; Caprio, Sonia.

In: Pediatric Research, Vol. 47, No. 5, 05.2000, p. 628-633.

Research output: Contribution to journalArticle

Heptulla, RA, Tamborlane, WV, Cavaghan, M, Bronson, M, Limb, C, Ma, YZ, Sherwin, RS & Caprio, S 2000, 'Augmentation of alimentary insulin secretion despite similar gastric inhibitory peptide (GIP) responses in juvenile obesity', Pediatric Research, vol. 47, no. 5, pp. 628-633.
Heptulla RA, Tamborlane WV, Cavaghan M, Bronson M, Limb C, Ma YZ et al. Augmentation of alimentary insulin secretion despite similar gastric inhibitory peptide (GIP) responses in juvenile obesity. Pediatric Research. 2000 May;47(5):628-633.
Heptulla, Rubina A. ; Tamborlane, William V. ; Cavaghan, Melissa ; Bronson, Mary ; Limb, Charles ; Ma, Yong Zhan ; Sherwin, Robert S. ; Caprio, Sonia. / Augmentation of alimentary insulin secretion despite similar gastric inhibitory peptide (GIP) responses in juvenile obesity. In: Pediatric Research. 2000 ; Vol. 47, No. 5. pp. 628-633.
@article{6c27001469d44926a9f91b733370f346,
title = "Augmentation of alimentary insulin secretion despite similar gastric inhibitory peptide (GIP) responses in juvenile obesity",
abstract = "Insulin secretion rates are greater after oral glucose than after parenteral administration of an equivalent glucose load. This augmented β- 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 β-cell stimulation may be independent of the increased release of GIP.",
author = "Heptulla, {Rubina A.} and Tamborlane, {William V.} and Melissa Cavaghan and Mary Bronson and Charles Limb and Ma, {Yong Zhan} and Sherwin, {Robert S.} and Sonia Caprio",
year = "2000",
month = "5",
language = "English (US)",
volume = "47",
pages = "628--633",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Augmentation of alimentary insulin secretion despite similar gastric inhibitory peptide (GIP) responses in juvenile obesity

AU - Heptulla, Rubina A.

AU - Tamborlane, William V.

AU - Cavaghan, Melissa

AU - Bronson, Mary

AU - Limb, Charles

AU - Ma, Yong Zhan

AU - Sherwin, Robert S.

AU - Caprio, Sonia

PY - 2000/5

Y1 - 2000/5

N2 - Insulin secretion rates are greater after oral glucose than after parenteral administration of an equivalent glucose load. This augmented β- 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 β-cell stimulation may be independent of the increased release of GIP.

AB - Insulin secretion rates are greater after oral glucose than after parenteral administration of an equivalent glucose load. This augmented β- 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 β-cell stimulation may be independent of the increased release of GIP.

UR - http://www.scopus.com/inward/record.url?scp=0034059298&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034059298&partnerID=8YFLogxK

M3 - Article

C2 - 10813588

AN - SCOPUS:0034059298

VL - 47

SP - 628

EP - 633

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 5

ER -