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Glucose and fatty acids synergistically and reversibly promote beta cell proliferation in rats

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Abstract Aims/hypothesis The mechanisms underlying pancreatic islet mass expansion have attracted considerable interest as potential therapeutic targets to prevent or delay the onset of type 2 diabetes. While several factors promoting beta cell proliferation have been identified, in the context of nutrient excess the roles of glucose or NEFA in relation to insulin resistance remain unclear. Herewe tested the hypothesisthat glucose and NEFA synergistically and reversibly promote beta cell proliferation in the context of nutrient-induced insulin resistance. Methods Using 72 h infusions of glucose (GLU) or the oleate-enriched lipid emulsion ClinOleic (CLI), singly or in combination, we assessed beta cell proliferation, islet mass and insulin sensitivity in male Lewis rats. The effects of nutrients and endogenous circulating factors were examined in isolated and transplanted islets. Reversibility was studied 3 and 6 days after the end of the infusion. Results GLUinfusions modestlystimulated betacellproliferation, CLI alone had no effect and GLU+CLI infusions markedly stimulated beta cell proliferation. Insulin sensitivity was equally decreased in GLU and GLU+CLI infusions. GLU+CLI infusions also stimulated beta cell proliferation in islets transplanted under the kidney capsule, albeit to a lesser extent compared with endogenous islets. Ex vivo, the combination of glucose and NEFA enhanced beta cell proliferation in rat and human islets independently from secreted insulin, and serum from GLU+CLI-infused rats potentiated the effect of glucose. Glucose tolerance, beta cell proliferation and islet mass were all restored to normal levels 6 days after termination of the infusion. Conclusions/interpretation Glucose and NEFA synergistically and reversibly promote beta cell proliferation in part via direct action on the beta cell and independently from secreted insulin.
Keywords Animal .Insulinsensitivityandresistance .Islets . Metabolicphysiologyinvivo .Rat

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Judul Seri

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No. Panggil

artikel

Penerbit

USA : Springer., 2017

Deskripsi Fisik

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Bahasa

English

ISBN/ISSN

DOI 10.1007/s00125-0

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NONE

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Tipe Media

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Tipe Pembawa

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Edisi

Diabetologia (2017) 60:879–888

Subjek

Medicine
Glucose and fatty acids

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