Acute elevation of NEFA causes hyperinsulinemia without effect on insulin secretion rate in healthy human subjects

Beate Balent, Gayotri Goswami, George Goodloe, Eduard Rogatsky, Olimpia Rauta, Robert Nezami, Lisa Mints, Ruth Hogue Angeletti, Daniel T. Stein

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Abstract

Increased circulating levels of nonesterified free fatty acids (NEFA) have been observed in such hyperinsulinemic states as obesity, impaired glucose tolerance, diabetes, and dyslipidemia where they have been causally linked to the development of insulin resistance and hyperinsulinemia. The concentration of NEFA in plasma is believed to have direct modifying effects on insulin secretion and clearance. It remains controversial whether acute increases in NEFA potentiate insulin secretion in human subjects. We studied the effect of an acute elevation of NEFA during lipid-heparin infusion compared to a glycerol-only control on glucose-stimulated insulin secretion and clearance during a 120-min hyperglycemic (10 mM) clamp in 7 healthy normoglucose-tolerant volunteers. The metabolic clearance rate of C-peptide (MCRCP) was measured in each subject during the study by simultaneous infusion of C-peptide. Insulin secretion rate (ISR) was calculated from deconvolution of C-peptide data after correction for the rate of C-peptide infusion. Clearance rate of insulin (MCRINS) was calculated based upon endogenous ISR. Plasma glucose (mg/dL): basal (90-115 min) 90.2 ± 2.8 vs. 90.2 ± 2.3; clamp (150-240 min) 180.5 ± 2.8 vs. 180.9 ± 1.3. Plasma insulin (pmol/L): prehasal (fasting) 29.6 ± 10.0 vs. 29.8 ± 10.6; basal (90-115 min) 30.1 ± 9.2 vs. 34.5 ± 12.1; second phase clamp (210-240 min) 127.6 ± 18.2 vs. 182.5 ± 17.3*. Plasma NEFA (mM): prebasal 0.47 ± 0.08 vs. 0.52 ± 0.09; basal 0.35 ± 0.05 vs. 0.98 ± 0.02*; clamp (122-240 min) 0.06 ± 0.02 vs. 0.77 ± 0.06*. ISR (pmol/min): prehasal 72.7 ± 7.5 vs. 72.0 ± 7.9; second phase clamp (210-240 min) 268.5 ± 27.2 vs. 200.2 ± 23.7. MCRINS (mL/min): prehasal 3393 ± 488 vs. 3370 ± 511; clamp 2284 ± 505 vs. 1214 ± 153* (*p < 0.05 glycerol vs. intralipid/heparin). This study demonstrates that acute NEFA elevation causes hyperinsulinemia due to a significant decrease in systemic insulin clearance without increasing rates of insulin secretion.

Original languageEnglish (US)
Pages (from-to)535-543
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume967
StatePublished - 2002

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Hyperinsulinism
Nonesterified Fatty Acids
Healthy Volunteers
Insulin
Clamping devices
C-Peptide
Plasmas
Glucose
Glycerol
Heparin
Elevation
Secretion
Causes
Fatty Acids
Human Subjects
Metabolic Clearance Rate
Glucose Intolerance
Deconvolution
Medical problems
Dyslipidemias

Keywords

  • C-peptide
  • Free fatty acids
  • Insulin secretion
  • NEFA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Acute elevation of NEFA causes hyperinsulinemia without effect on insulin secretion rate in healthy human subjects. / Balent, Beate; Goswami, Gayotri; Goodloe, George; Rogatsky, Eduard; Rauta, Olimpia; Nezami, Robert; Mints, Lisa; Angeletti, Ruth Hogue; Stein, Daniel T.

In: Annals of the New York Academy of Sciences, Vol. 967, 2002, p. 535-543.

Research output: Contribution to journalArticle

Balent, B, Goswami, G, Goodloe, G, Rogatsky, E, Rauta, O, Nezami, R, Mints, L, Angeletti, RH & Stein, DT 2002, 'Acute elevation of NEFA causes hyperinsulinemia without effect on insulin secretion rate in healthy human subjects', Annals of the New York Academy of Sciences, vol. 967, pp. 535-543.
Balent, Beate ; Goswami, Gayotri ; Goodloe, George ; Rogatsky, Eduard ; Rauta, Olimpia ; Nezami, Robert ; Mints, Lisa ; Angeletti, Ruth Hogue ; Stein, Daniel T. / Acute elevation of NEFA causes hyperinsulinemia without effect on insulin secretion rate in healthy human subjects. In: Annals of the New York Academy of Sciences. 2002 ; Vol. 967. pp. 535-543.
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T1 - Acute elevation of NEFA causes hyperinsulinemia without effect on insulin secretion rate in healthy human subjects

AU - Balent, Beate

AU - Goswami, Gayotri

AU - Goodloe, George

AU - Rogatsky, Eduard

AU - Rauta, Olimpia

AU - Nezami, Robert

AU - Mints, Lisa

AU - Angeletti, Ruth Hogue

AU - Stein, Daniel T.

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N2 - Increased circulating levels of nonesterified free fatty acids (NEFA) have been observed in such hyperinsulinemic states as obesity, impaired glucose tolerance, diabetes, and dyslipidemia where they have been causally linked to the development of insulin resistance and hyperinsulinemia. The concentration of NEFA in plasma is believed to have direct modifying effects on insulin secretion and clearance. It remains controversial whether acute increases in NEFA potentiate insulin secretion in human subjects. We studied the effect of an acute elevation of NEFA during lipid-heparin infusion compared to a glycerol-only control on glucose-stimulated insulin secretion and clearance during a 120-min hyperglycemic (10 mM) clamp in 7 healthy normoglucose-tolerant volunteers. The metabolic clearance rate of C-peptide (MCRCP) was measured in each subject during the study by simultaneous infusion of C-peptide. Insulin secretion rate (ISR) was calculated from deconvolution of C-peptide data after correction for the rate of C-peptide infusion. Clearance rate of insulin (MCRINS) was calculated based upon endogenous ISR. Plasma glucose (mg/dL): basal (90-115 min) 90.2 ± 2.8 vs. 90.2 ± 2.3; clamp (150-240 min) 180.5 ± 2.8 vs. 180.9 ± 1.3. Plasma insulin (pmol/L): prehasal (fasting) 29.6 ± 10.0 vs. 29.8 ± 10.6; basal (90-115 min) 30.1 ± 9.2 vs. 34.5 ± 12.1; second phase clamp (210-240 min) 127.6 ± 18.2 vs. 182.5 ± 17.3*. Plasma NEFA (mM): prebasal 0.47 ± 0.08 vs. 0.52 ± 0.09; basal 0.35 ± 0.05 vs. 0.98 ± 0.02*; clamp (122-240 min) 0.06 ± 0.02 vs. 0.77 ± 0.06*. ISR (pmol/min): prehasal 72.7 ± 7.5 vs. 72.0 ± 7.9; second phase clamp (210-240 min) 268.5 ± 27.2 vs. 200.2 ± 23.7. MCRINS (mL/min): prehasal 3393 ± 488 vs. 3370 ± 511; clamp 2284 ± 505 vs. 1214 ± 153* (*p < 0.05 glycerol vs. intralipid/heparin). This study demonstrates that acute NEFA elevation causes hyperinsulinemia due to a significant decrease in systemic insulin clearance without increasing rates of insulin secretion.

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