Delayed insulin absorption correlates with alterations in subcutaneous depot kinetics in rats with diet‐induced obesity
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Delayed insulin absorption correlates with alterations in subcutaneous depot kinetics in rats with diet‐induced obesity. / Gradel, Anna Katrina Jógvansdóttir; Porsgaard, Trine ; Brockhoff, Per Mikael Bruun; Seested, Torben; Lykkesfeldt, Jens; Refsgaard, Hanne H. F.
I: Obesity Science & Practice, Bind 5, Nr. 3, 2019, s. 281-288.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Delayed insulin absorption correlates with alterations in subcutaneous depot kinetics in rats with diet‐induced obesity
AU - Gradel, Anna Katrina Jógvansdóttir
AU - Porsgaard, Trine
AU - Brockhoff, Per Mikael Bruun
AU - Seested, Torben
AU - Lykkesfeldt, Jens
AU - Refsgaard, Hanne H. F.
PY - 2019
Y1 - 2019
N2 - ObjectiveObesity is associated with delayed insulin absorption upon subcutaneous (s.c.) dosing in humans. The aim of this study was to investigate whether alterations in depot structure and kinetics of the s.c. injection depot contribute to this delay.MethodsRats fed a high‐fat diet (HFD) and low‐fat diet (LFD) were included in a series of insulin pharmacokinetic and imaging studies. Injection depots were visualized with micro X‐ray computed tomography imaging upon s.c. administration of insulin aspart mixed with the contrast agent iomeprol, and insulin aspart exposure was measured by means of luminescent oxygen channelling immunoassay.ResultsBody weight and fat mass were increased in rats fed an HFD vs. LFD (p < 0.05), whereas the lean mass was not. The HFD group exhibited delayed insulin absorption from the s.c. tissue (p < 0.001). This delay was associated with smaller injection depots upon s.c. dosing (p < 0.05) and correlated with a slower depot disappearance from the s.c. tissue (p < 0.05) compared with the LFD group. Depot disappearance from the s.c. tissue was inversely correlated with body fat mass (p < 0.05).ConclusionsAlterations in s.c. injection depot structure and kinetics may play a role in the obesity‐associated delay in insulin absorption.
AB - ObjectiveObesity is associated with delayed insulin absorption upon subcutaneous (s.c.) dosing in humans. The aim of this study was to investigate whether alterations in depot structure and kinetics of the s.c. injection depot contribute to this delay.MethodsRats fed a high‐fat diet (HFD) and low‐fat diet (LFD) were included in a series of insulin pharmacokinetic and imaging studies. Injection depots were visualized with micro X‐ray computed tomography imaging upon s.c. administration of insulin aspart mixed with the contrast agent iomeprol, and insulin aspart exposure was measured by means of luminescent oxygen channelling immunoassay.ResultsBody weight and fat mass were increased in rats fed an HFD vs. LFD (p < 0.05), whereas the lean mass was not. The HFD group exhibited delayed insulin absorption from the s.c. tissue (p < 0.001). This delay was associated with smaller injection depots upon s.c. dosing (p < 0.05) and correlated with a slower depot disappearance from the s.c. tissue (p < 0.05) compared with the LFD group. Depot disappearance from the s.c. tissue was inversely correlated with body fat mass (p < 0.05).ConclusionsAlterations in s.c. injection depot structure and kinetics may play a role in the obesity‐associated delay in insulin absorption.
U2 - 10.1002/osp4.326
DO - 10.1002/osp4.326
M3 - Journal article
C2 - 31275602
VL - 5
SP - 281
EP - 288
JO - Obesity Science & Practice
JF - Obesity Science & Practice
SN - 2055-2238
IS - 3
ER -
ID: 210734521