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Nutrient Regulation of Insulin Secretion and β-Cell Functional Integrity

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The Islets of Langerhans

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 654))

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:

CarnitinePalmitoyl Transferase 1

DAG:

diacylglycerol

FFA:

free fatty acid

GLP-1:

glucagon-like peptide-1

GIP:

glucose-dependent insulinotropic polypeptide

GSIS:

glucose-stimulated insulin secretion

Gly3P:

glycerol-3-phosphate

LC-acylCoA:

long-chain acyl-CoA

MCF:

metabolic coupling factors

PKA:

protein kinase A

PKC:

protein kinase C

PLC:

phospholipase C

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Authors and Affiliations

  1. School of Biomolecular and Biomedical Sciences, Conway Institute, UCD Dublin, Belfield, Dublin 4, Ireland

    Philip Newsholme & Celine Gaudel

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

    Neville H. McClenaghan

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  1. Philip Newsholme
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Correspondence to Philip Newsholme .

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  1. Dept. Clinical Research & Education, Karolinska Institutet, Stockholm, 118 83, Sweden

    Md. Shahidul Islam

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Newsholme, P., Gaudel, C., McClenaghan, N.H. (2010). Nutrient Regulation of Insulin Secretion and β-Cell Functional Integrity. In: Islam, M. (eds) The Islets of Langerhans. Advances in Experimental Medicine and Biology, vol 654. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3271-3_6

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