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Glucagon increases ...
Glucagon increases insulin levels by stimulating insulin secretion without effect on insulin clearance in mice
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- Song, Gina (author)
- University of Southern California
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- Pacini, Giovanni (author)
- CNR Institute of Neuroscience, Pisa
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- Ahrén, Bo (author)
- Lund University,Lunds universitet,Diabetes,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- D'Argenio, David Z. (author)
- University of Southern California
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(creator_code:org_t)
- Elsevier BV, 2017
- 2017
- English 6 s.
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In: Peptides. - : Elsevier BV. - 0196-9781. ; 88, s. 74-79
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Abstract
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- Circulating insulin is dependent on a balance between insulin appearance through secretion and insulin clearance. However, to what extent changes in insulin clearance contribute to the increased insulin levels after glucagon administration is not known. This study therefore assessed and quantified any potential effect of glucagon on insulin kinetics in mice. Prehepatic insulin secretion in mice was first estimated following glucose (0.35 g/kg i.v.) and following glucose plus glucagon (10 μg/kg i.v.) using deconvolution of plasma C-peptide concentrations. Plasma concentrations of glucose, insulin, and glucagon were then measured simultaneously in individual mice following glucose alone or glucose plus glucagon (pre dose and at 1, 5, 10, 20 min post). Using the previously determined insulin secretion profiles and the insulin concentration-time measurements, a population modeling analysis was applied to estimate the one-compartment kinetics of insulin disposition with and without glucagon. Glucagon with glucose significantly enhanced prehepatic insulin secretion (Cmax and AUC0-20) compared to that with glucose alone (p < 0.0001). From the modeling analysis, the population mean and between-animal SD of insulin clearance was 6.4 ± 0.34 mL/min for glucose alone and 5.8 ± 1.5 mL/min for glucagon plus glucose, with no significant effect of glucagon on mean insulin clearance. Therefore, we conclude that the enhancement of circulating insulin after glucagon administration is solely due to stimulated insulin secretion.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Glucagon
- Insulin clearance
- Insulin secretion
- Population analysis
Publication and Content Type
- art (subject category)
- ref (subject category)
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