Glucagon-like peptide 1 and fatty acids amplify pulsatile insulin secretion from perifused rat islets

Barbara A CUNNINGHAM; Ann-Marie T RICHARD; Joseph S DILLON; Jennifer T DALEY; Vildan N CIVELEK; Jude T DEENEY; Gordon C YANEY; Barbara E CORKEY; Keith TORNHEIM

doi:10.1042/bj20021196

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Glucagon-like peptide 1 and fatty acids amplify pulsatile insulin secretion from perifused rat islets

Journal article

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Glucagon-like peptide 1 and fatty acids amplify pulsatile insulin secretion from perifused rat islets

Barbara A CUNNINGHAM, Ann-Marie T RICHARD, Joseph S DILLON, Jennifer T DALEY, Vildan N CIVELEK, Jude T DEENEY, Gordon C YANEY, Barbara E CORKEY and Keith TORNHEIM

Biochemical journal, Vol.369(1), pp.173-178

01/01/2003

DOI: 10.1042/bj20021196

PMCID: PMC1223070

PMID: 12356335

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Abstract

Glucose-induced insulin secretion from isolated, perifused rat islets is pulsatile with a period of about 5—10min, similar to the insulin oscillations that are seen in healthy humans but which are impaired in Type II diabetes. We evaluated the pattern of enhancement by the potent incretin, glucagon-like peptide 1 (GLP-1). GLP-1 increased the amplitude of pulses and the magnitude of insulin secretion from the perifused islets, without affecting the average time interval between pulses. Forskolin and the phosphodiesterase inhibitor isobutylmethylxanthine had the same effect, suggesting that the effect was due to elevated cAMP levels. The possibility that cAMP might enhance the amplitude of pulses by reducing phosphofructo-2-kinase (PFK-2) activity was eliminated when the liver isoform of PFK-2 was shown to be absent from β-cells. The possibility that cAMP enhanced pulsatile secretion, at least in part, by stimulating lipolysis was supported by the observations that added oleate had a similar effect on secretion, and that the incretin effect of GLP-1 was inhibited by the lipase inhibitor orlistat. These data show that the physiological incretin GLP-1 preserves and enhances normal pulsatile insulin secretion, which may be essential in proposed therapeutic uses of GLP-1 or its analogues.

Details

Title: Subtitle: Glucagon-like peptide 1 and fatty acids amplify pulsatile insulin secretion from perifused rat islets
Creators: Barbara A CUNNINGHAM - Department of Biochemistry, Boston University Medical Center, Room 815, 650 Albany Street, Boston, MA 02118, U.S.A., The Obesity Research Center, Evans Department of Medicine, Boston University Medical Center, 650 Albany Street, Boston, MA 02118, U.S.A
Ann-Marie T RICHARD - Department of Biochemistry, Boston University Medical Center, Room 815, 650 Albany Street, Boston, MA 02118, U.S.A., Department of Pathology, Boston University Medical Center, 715 Albany Street, Boston, MA 02118, U.S.A., The Obesity Research Center, Evans Department of Medicine, Boston University Medical Center, 650 Albany Street, Boston, MA 02118, U.S.A
Joseph S DILLON - Department of Medicine, University of Iowa, Iowa City, IA 52246, U.S.A
Jennifer T DALEY - Department of Biochemistry, Boston University Medical Center, Room 815, 650 Albany Street, Boston, MA 02118, U.S.A
Vildan N CIVELEK - The Obesity Research Center, Evans Department of Medicine, Boston University Medical Center, 650 Albany Street, Boston, MA 02118, U.S.A
Jude T DEENEY - The Obesity Research Center, Evans Department of Medicine, Boston University Medical Center, 650 Albany Street, Boston, MA 02118, U.S.A
Gordon C YANEY - The Obesity Research Center, Evans Department of Medicine, Boston University Medical Center, 650 Albany Street, Boston, MA 02118, U.S.A
Barbara E CORKEY - Department of Biochemistry, Boston University Medical Center, Room 815, 650 Albany Street, Boston, MA 02118, U.S.A., The Obesity Research Center, Evans Department of Medicine, Boston University Medical Center, 650 Albany Street, Boston, MA 02118, U.S.A
Keith TORNHEIM - Department of Biochemistry, Boston University Medical Center, Room 815, 650 Albany Street, Boston, MA 02118, U.S.A., The Obesity Research Center, Evans Department of Medicine, Boston University Medical Center, 650 Albany Street, Boston, MA 02118, U.S.A
Resource Type: Journal article
Publication Details: Biochemical journal, Vol.369(1), pp.173-178
DOI: 10.1042/bj20021196
PMID: 12356335
PMCID: PMC1223070
ISSN: 0264-6021
eISSN: 1470-8728
Language: English
Date published: 01/01/2003
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094743302771

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