Increased amino acid supply potentiates glucose-stimulated insulin secretion but does not increase β-cell mass in fetal sheep

Monika M. Gadhia, Anne M. Maliszewski, Meghan C. O'Meara, Stephanie R. Thorn, Jinny R. Lavezzi, Sean W Limesand, William W. Hay, Laura D. Brown, Paul J. Rozance

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Amino acids and glucose acutely stimulate fetal insulin secretion. In isolated adult pancreatic islets, amino acids potentiate glucose-stimulated insulin secretion (GSIS), but whether amino acids have this same effect in the fetus is unknown. Therefore, we tested the effects of increased fetal amino acid supply on GSIS and morphology of the pancreas. We hypothesized that increasing fetal amino acid supply would potentiate GSIS. Singleton fetal sheep received a direct intravenous infusion of an amino acid mixture (AA) or saline (CON) for 10-14 days during late gestation to target a 25-50% increase in fetal branched-chain amino acids (BCAA). Early-phase GSIS increased 150% in the AA group (P < 0.01), and this difference was sustained for the duration of the hyperglycemic clamp (105 min) (P < 0.05). Glucose-potentiated arginine-stimulated insulin secretion (ASIS), pancreatic insulin content, and pancreatic glucagon content were similar between groups. β-Cell mass and area were unchanged between groups. Baseline and arginine-stimulated glucagon concentrations were increased in the AA group (P < 0.05). Pancreatic α-cell mass and area were unchanged. Fetal and pancreatic weights were similar. We conclude that a sustained increase of amino acid supply to the normally growing lategestation fetus potentiated fetal GSIS but did not affect the morphology or insulin content of the pancreas. We speculate that increased β-cell responsiveness (insulin secretion) following increased amino acid supply may be due to increased generation of secondary messengers in the β-cell. This may be enhanced by the paracrine action of glucagon on the β-cell.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume304
Issue number4
DOIs
StatePublished - Feb 15 2013

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Sheep
Insulin
Amino Acids
Glucose
Glucagon
Arginine
Pancreas
Fetus
Branched Chain Amino Acids
Fetal Weight
Islets of Langerhans
Intravenous Infusions
Pregnancy

Keywords

  • α-cell
  • Glucagon
  • Metabolism
  • Pancreas
  • Pregnancy

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Increased amino acid supply potentiates glucose-stimulated insulin secretion but does not increase β-cell mass in fetal sheep. / Gadhia, Monika M.; Maliszewski, Anne M.; O'Meara, Meghan C.; Thorn, Stephanie R.; Lavezzi, Jinny R.; Limesand, Sean W; Hay, William W.; Brown, Laura D.; Rozance, Paul J.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 304, No. 4, 15.02.2013.

Research output: Contribution to journalArticle

Gadhia, Monika M. ; Maliszewski, Anne M. ; O'Meara, Meghan C. ; Thorn, Stephanie R. ; Lavezzi, Jinny R. ; Limesand, Sean W ; Hay, William W. ; Brown, Laura D. ; Rozance, Paul J. / Increased amino acid supply potentiates glucose-stimulated insulin secretion but does not increase β-cell mass in fetal sheep. In: American Journal of Physiology - Endocrinology and Metabolism. 2013 ; Vol. 304, No. 4.
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AB - Amino acids and glucose acutely stimulate fetal insulin secretion. In isolated adult pancreatic islets, amino acids potentiate glucose-stimulated insulin secretion (GSIS), but whether amino acids have this same effect in the fetus is unknown. Therefore, we tested the effects of increased fetal amino acid supply on GSIS and morphology of the pancreas. We hypothesized that increasing fetal amino acid supply would potentiate GSIS. Singleton fetal sheep received a direct intravenous infusion of an amino acid mixture (AA) or saline (CON) for 10-14 days during late gestation to target a 25-50% increase in fetal branched-chain amino acids (BCAA). Early-phase GSIS increased 150% in the AA group (P < 0.01), and this difference was sustained for the duration of the hyperglycemic clamp (105 min) (P < 0.05). Glucose-potentiated arginine-stimulated insulin secretion (ASIS), pancreatic insulin content, and pancreatic glucagon content were similar between groups. β-Cell mass and area were unchanged between groups. Baseline and arginine-stimulated glucagon concentrations were increased in the AA group (P < 0.05). Pancreatic α-cell mass and area were unchanged. Fetal and pancreatic weights were similar. We conclude that a sustained increase of amino acid supply to the normally growing lategestation fetus potentiated fetal GSIS but did not affect the morphology or insulin content of the pancreas. We speculate that increased β-cell responsiveness (insulin secretion) following increased amino acid supply may be due to increased generation of secondary messengers in the β-cell. This may be enhanced by the paracrine action of glucagon on the β-cell.

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