WFRF:(Omar Bilal)
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- Ahlkvist, LindaLund University,Lunds universitet,Medicin/akutsjukvård, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine (author)
Evidence for neural contribution to islet effects of DPP-4 inhibition in mice
- Article/chapterEnglish2016
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- Elsevier BV,2016
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- LIBRIS-ID:oai:lup.lub.lu.se:e453dbe3-e1ab-49e7-9482-c0db8756ae29
- https://lup.lub.lu.se/record/e453dbe3-e1ab-49e7-9482-c0db8756ae29URI
- https://doi.org/10.1016/j.ejphar.2016.03.030DOI
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- Language:English
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- It has been suggested that neural mechanisms may contribute to effects of the incretin hormones, and, therefore, also to the effects of dipeptidyl peptidase (DPP-4) inhibition. We therefore examined whether muscarinic mechanisms are involved in the stimulation of insulin secretion by DPP-4 inhibition. Fasted, anesthetized mice were given intraperitoneal saline or the muscarinic antagonist atropine (5mg/kg) before duodenal glucose (75mg/mouse), with or without the DPP-4 inhibitor NVPDPP728 (0.095mg/mouse), or before intravenous glucose (0.35g/kg) with or without co-administration with GLP-1 or glucose-dependent insulinotropic polypeptide (GIP) (both 3nmol/kg). Furthermore, isolated islets were incubated (1h) in 2.8 and 11.1mM glucose, with or without GIP or GLP-1 (both 100nM), in the presence or absence of atropine (100µM). Duodenal glucose increased circulating insulin and this effect was potentiated by DPP-4 inhibition. The increase in insulin achieved by DPP-4 inhibition was reduced by atropine by approximately 35%. Duodenal glucose also elicited an increase in circulating intact GLP-1 and GIP and this was augmented by DPP-4 inhibition, but these effects were not affected by atropine. Atropine did also not affect the augmentation by GLP-1 and GIP on glucose-stimulated insulin secretion from isolated islets. Based on these findings, we suggest that muscarinic mechanisms contribute to the stimulation of insulin secretion by DPP-4 inhibition through neural effects induced by GLP-1 and GIP whereas neural effects do not affect the levels of GLP-1 or GIP or the islet effects of the two incretin hormones.
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- Omar, BilalLund University,Lunds universitet,Medicin/akutsjukvård, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-bor (author)
- Pacini, GiovanniCNR: National Research Council of Italy (author)
- Ahrén, BoLund University,Lunds universitet,Medicin/akutsjukvård, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-bah (author)
- Medicin/akutsjukvård, LundSektion II (creator_code:org_t)
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- In:European Journal of Pharmacology: Elsevier BV780, s. 46-521879-07120014-2999
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