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The incretin effect in female mice with double deletion of GLP-1 and GIP receptors

Ahrén, Bo (författare)
Lund University,Lunds universitet,Medicin/akutsjukvård, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Diabetes,Forskargrupper vid Lunds universitet,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
Yamada, Yuichiro (författare)
Aichi Cancer Center Research Institute
Seino, Yutaka (författare)
Kansai Electric Power Hospital
 (creator_code:org_t)
2019-12-23
2020
Engelska.
Ingår i: Journal of the Endocrine Society. - : The Endocrine Society. - 2472-1972. ; 4:2
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • To establish the contribution of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) for the incretin effect after oral glucose, studies were undertaken in female mice with genetic deletion of receptors for GIP and GLP-1 (double incretin receptor knockout [DIRKO] mice) and their wild-type (WT) counterparts. Insulin secretion was explored after oral glucose (doses ranging from 0 to 100 mg), after intravenous glucose (doses ranging from 0 to 0.75 g/kg), and after oral and intravenous glucose at matching circulating glucose. DIRKO mice had glucose intolerance after oral glucose challenges in association with impaired beta-cell function. Suprabasal area under the curve for C-peptide (AUCC-peptide) correlated linearly with suprabasal AUCglucose both in WT (r = 0.942, P = .017) and DIRKO mice (r = 0.972, P = .006). The slope of this regression was lower in DIRKO than in WT mice (0.012 ± 0.006 vs 0.031 ± 0.006 nmol C-peptide/mmol glucose, P = .042). In contrast, there was no difference in the insulin response to intravenous glucose between WT and DIRKO mice. Furthermore, oral and intravenous glucose administration at matching glucose levels showed that the augmentation of insulin secretion after oral glucose (the incretin effect) in WT mice (11.8 ± 2.3 nmol/L min) was entirely absent in DIRKO mice (3.3 ± 1.2 nmol/L min). We conclude that GIP and GLP-1 are required for normal glucose tolerance and beta-cell function after oral glucose in mice, that they are the sole incretin hormones after oral glucose at higher dose levels, and that they contribute by 65% to insulin secretion after oral glucose.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Animal models
Glucose tolerance
Incretin effect
Incretin hormones
Insulin secretion

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Ahrén, Bo
Yamada, Yuichiro
Seino, Yutaka
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MEDICIN OCH HÄLSOVETENSKAP
MEDICIN OCH HÄLS ...
och Klinisk medicin
och Endokrinologi oc ...
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Lunds universitet

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