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Islets of Langerhans pp 129–156Cite as

(Dys)Regulation of Insulin Secretion by Macronutrients

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Abstract

Pancreatic β-cells are often referred to as “fuel sensors” as they continually monitor and respond to dietary nutrients, under the modulation of additional neurohormonal signals, in order to secrete insulin to best meet the needs of the organism. β-Cell nutrient sensing requires metabolic activation, resulting in production of stimulus-secretion coupling signals that promote insulin biosynthesis and release. The primary stimulus for insulin secretion is glucose, and islet β-cells are particularly responsive to this important nutrient secretagogue. It is important to consider individual effects of different classes of nutrient or other physiological or pharmacological agents on metabolism and insulin secretion. However, given that β-cells are continually exposed to a complex milieu of nutrients and other circulating factors, it is important to also acknowledge and examine the interplay between glucose metabolism and that of the two other primary nutrient classes, the amino acids and fatty acids. It is the mixed nutrient sensing and outputs of glucose, amino and fatty acid metabolism that generate the metabolic coupling factors (MCFs) involved in signaling for insulin exocytosis. Primary MCFs in the β-cell include ATP, NADPH, glutamate, long chain acyl-CoA and diacylglycerol and are discussed in detail in this article.

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Abbreviations

ACC:

Acetyl-CoA carboxylase

CPT-1:

Carnitine Palmitoyl Transferase 1

DAG:

Diacylglycerol

FFA:

Free fatty acid

GIP:

Glucose-dependent insulinotropic polypeptide

GLP-1:

Glucagon-like peptide-1

Gly3P:

Glycerol-3-phosphate

GSIS:

Glucose-stimulated insulin secretion

LC-acyl:

CoA long-chain acyl-CoA

MCF:

Metabolic coupling factors

PI3K:

Phosphatidylinositide-3-kinases

PKA:

Protein kinase A

PKC:

Protein kinase C

PLC:

Phospholipase C

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Authors and Affiliations

  1. School of Biomedical Sciences, CHIRI Biosciences, Curtin University, Belfield, Perth, WA, Australia

    Philip Newsholme & Kevin Keane

  2. INSERM U1065, Centre Mediterraneen de Medicine Moleculaire, C3M, Batiment Archimed, 151 Av Saint Antoine de Ginestiere, Nice, Cedex 2, France

    Celine Gaudel

  3. School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, Londonderry, Northern Ireland

    Neville McClenaghan

Authors
  1. Philip Newsholme
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  2. Kevin Keane
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  3. Celine Gaudel
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  4. Neville McClenaghan
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Corresponding author

Correspondence to Philip Newsholme .

Editor information

Editors and Affiliations

  1. Department of Clinical Sciences and Education, Sodersjukhuset, Karolinska Institutet, Stockholm, Sweden

    Md. Shahidul Islam

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Newsholme, P., Keane, K., Gaudel, C., McClenaghan, N. (2015). (Dys)Regulation of Insulin Secretion by Macronutrients. In: Islam, M. (eds) Islets of Langerhans. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6686-0_4

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