Exogenous insulin enhances glucose-stimulated insulin response in healthy humans independent of changes in free fatty acids

Ximena Lopez, Aaron Cypess, Raquel Manning, Sheila O'Shea, Rohit N. Kulkarni, Allison B. Goldfine

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Context: Islet β-cells express both insulin receptors and insulin signaling proteins. Recent studies suggest insulin signaling is physiologically important for glucose sensing. Objective: Preexposure to insulin enhances glucose-stimulated insulin secretion (GSIS) in healthy humans. We evaluated whether the effect of insulin to potentiate GSIS is modulated through regulation of free fatty acids (FFA). Design and Setting: Subjects were studied on three occasions in this single-site study at an academic institution clinical research center. Patients: Subjects included nine healthy volunteers. Interventions: Glucose-induced insulin response was assessed on three occasions after 4 h saline (low insulin/sham) or isoglycemic-hyperinsulinemic (high insulin) clamps with or without intralipid and heparin infusion, using B28 Asp-insulin that could be distinguished from endogenous insulin immunologically. During the last 80 min of all three clamps, additional glucose was administered to stimulate insulin secretion (GSIS) with glucose concentrations maintained at similar concentrations during all studies. Main Outcome Measure: β-Cell response to glucose stimulation was assessed. Results: Preexposure to exogenous insulin increased the endogenous insulin-secretory response to glucose by 32% compared with sham clamp (P = 0.001). This was accompanied by a drop in FFA during hyperinsulinemic clamp compared with the sham clamp (0.06 ± 0.02 vs. 0.60 ± 0.09 mEq/liter, respectively), which was prevented during the hyperinsulinemic clamp with intralipid/heparin infusion (1.27 ± 0.17 mEq/liter). After preexposure to insulin with intralipid/heparin infusion to maintain FFA concentration, GSIS was 21% higher compared with sham clamp (P < 0.04) and similar to preexposure to insulin without intralipid/heparin (P = 0.2). Conclusions: Insulin potentiates glucose-stimulated insulin response independent of FFA concentrations in healthy humans.

Original languageEnglish (US)
Pages (from-to)3811-3821
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number12
DOIs
StatePublished - Dec 2011

Fingerprint

Nonesterified Fatty Acids
Insulin
Glucose
Clamping devices
Heparin
Insulin Aspart
Glucose Clamp Technique
Insulin Receptor
Islets of Langerhans

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Exogenous insulin enhances glucose-stimulated insulin response in healthy humans independent of changes in free fatty acids. / Lopez, Ximena; Cypess, Aaron; Manning, Raquel; O'Shea, Sheila; Kulkarni, Rohit N.; Goldfine, Allison B.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 96, No. 12, 12.2011, p. 3811-3821.

Research output: Contribution to journalArticle

Lopez, Ximena ; Cypess, Aaron ; Manning, Raquel ; O'Shea, Sheila ; Kulkarni, Rohit N. ; Goldfine, Allison B. / Exogenous insulin enhances glucose-stimulated insulin response in healthy humans independent of changes in free fatty acids. In: Journal of Clinical Endocrinology and Metabolism. 2011 ; Vol. 96, No. 12. pp. 3811-3821.
@article{09cc2a3d2fdf42049e31c2a5bd1b6c86,
title = "Exogenous insulin enhances glucose-stimulated insulin response in healthy humans independent of changes in free fatty acids",
abstract = "Context: Islet β-cells express both insulin receptors and insulin signaling proteins. Recent studies suggest insulin signaling is physiologically important for glucose sensing. Objective: Preexposure to insulin enhances glucose-stimulated insulin secretion (GSIS) in healthy humans. We evaluated whether the effect of insulin to potentiate GSIS is modulated through regulation of free fatty acids (FFA). Design and Setting: Subjects were studied on three occasions in this single-site study at an academic institution clinical research center. Patients: Subjects included nine healthy volunteers. Interventions: Glucose-induced insulin response was assessed on three occasions after 4 h saline (low insulin/sham) or isoglycemic-hyperinsulinemic (high insulin) clamps with or without intralipid and heparin infusion, using B28 Asp-insulin that could be distinguished from endogenous insulin immunologically. During the last 80 min of all three clamps, additional glucose was administered to stimulate insulin secretion (GSIS) with glucose concentrations maintained at similar concentrations during all studies. Main Outcome Measure: β-Cell response to glucose stimulation was assessed. Results: Preexposure to exogenous insulin increased the endogenous insulin-secretory response to glucose by 32{\%} compared with sham clamp (P = 0.001). This was accompanied by a drop in FFA during hyperinsulinemic clamp compared with the sham clamp (0.06 ± 0.02 vs. 0.60 ± 0.09 mEq/liter, respectively), which was prevented during the hyperinsulinemic clamp with intralipid/heparin infusion (1.27 ± 0.17 mEq/liter). After preexposure to insulin with intralipid/heparin infusion to maintain FFA concentration, GSIS was 21{\%} higher compared with sham clamp (P < 0.04) and similar to preexposure to insulin without intralipid/heparin (P = 0.2). Conclusions: Insulin potentiates glucose-stimulated insulin response independent of FFA concentrations in healthy humans.",
author = "Ximena Lopez and Aaron Cypess and Raquel Manning and Sheila O'Shea and Kulkarni, {Rohit N.} and Goldfine, {Allison B.}",
year = "2011",
month = "12",
doi = "10.1210/jc.2011-0627",
language = "English (US)",
volume = "96",
pages = "3811--3821",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "12",

}

TY - JOUR

T1 - Exogenous insulin enhances glucose-stimulated insulin response in healthy humans independent of changes in free fatty acids

AU - Lopez, Ximena

AU - Cypess, Aaron

AU - Manning, Raquel

AU - O'Shea, Sheila

AU - Kulkarni, Rohit N.

AU - Goldfine, Allison B.

PY - 2011/12

Y1 - 2011/12

N2 - Context: Islet β-cells express both insulin receptors and insulin signaling proteins. Recent studies suggest insulin signaling is physiologically important for glucose sensing. Objective: Preexposure to insulin enhances glucose-stimulated insulin secretion (GSIS) in healthy humans. We evaluated whether the effect of insulin to potentiate GSIS is modulated through regulation of free fatty acids (FFA). Design and Setting: Subjects were studied on three occasions in this single-site study at an academic institution clinical research center. Patients: Subjects included nine healthy volunteers. Interventions: Glucose-induced insulin response was assessed on three occasions after 4 h saline (low insulin/sham) or isoglycemic-hyperinsulinemic (high insulin) clamps with or without intralipid and heparin infusion, using B28 Asp-insulin that could be distinguished from endogenous insulin immunologically. During the last 80 min of all three clamps, additional glucose was administered to stimulate insulin secretion (GSIS) with glucose concentrations maintained at similar concentrations during all studies. Main Outcome Measure: β-Cell response to glucose stimulation was assessed. Results: Preexposure to exogenous insulin increased the endogenous insulin-secretory response to glucose by 32% compared with sham clamp (P = 0.001). This was accompanied by a drop in FFA during hyperinsulinemic clamp compared with the sham clamp (0.06 ± 0.02 vs. 0.60 ± 0.09 mEq/liter, respectively), which was prevented during the hyperinsulinemic clamp with intralipid/heparin infusion (1.27 ± 0.17 mEq/liter). After preexposure to insulin with intralipid/heparin infusion to maintain FFA concentration, GSIS was 21% higher compared with sham clamp (P < 0.04) and similar to preexposure to insulin without intralipid/heparin (P = 0.2). Conclusions: Insulin potentiates glucose-stimulated insulin response independent of FFA concentrations in healthy humans.

AB - Context: Islet β-cells express both insulin receptors and insulin signaling proteins. Recent studies suggest insulin signaling is physiologically important for glucose sensing. Objective: Preexposure to insulin enhances glucose-stimulated insulin secretion (GSIS) in healthy humans. We evaluated whether the effect of insulin to potentiate GSIS is modulated through regulation of free fatty acids (FFA). Design and Setting: Subjects were studied on three occasions in this single-site study at an academic institution clinical research center. Patients: Subjects included nine healthy volunteers. Interventions: Glucose-induced insulin response was assessed on three occasions after 4 h saline (low insulin/sham) or isoglycemic-hyperinsulinemic (high insulin) clamps with or without intralipid and heparin infusion, using B28 Asp-insulin that could be distinguished from endogenous insulin immunologically. During the last 80 min of all three clamps, additional glucose was administered to stimulate insulin secretion (GSIS) with glucose concentrations maintained at similar concentrations during all studies. Main Outcome Measure: β-Cell response to glucose stimulation was assessed. Results: Preexposure to exogenous insulin increased the endogenous insulin-secretory response to glucose by 32% compared with sham clamp (P = 0.001). This was accompanied by a drop in FFA during hyperinsulinemic clamp compared with the sham clamp (0.06 ± 0.02 vs. 0.60 ± 0.09 mEq/liter, respectively), which was prevented during the hyperinsulinemic clamp with intralipid/heparin infusion (1.27 ± 0.17 mEq/liter). After preexposure to insulin with intralipid/heparin infusion to maintain FFA concentration, GSIS was 21% higher compared with sham clamp (P < 0.04) and similar to preexposure to insulin without intralipid/heparin (P = 0.2). Conclusions: Insulin potentiates glucose-stimulated insulin response independent of FFA concentrations in healthy humans.

UR - http://www.scopus.com/inward/record.url?scp=83155165409&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=83155165409&partnerID=8YFLogxK

U2 - 10.1210/jc.2011-0627

DO - 10.1210/jc.2011-0627

M3 - Article

VL - 96

SP - 3811

EP - 3821

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 12

ER -