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Mol Metab. 2017 May 4;6(9):958-973. doi: 10.1016/j.molmet.2017.04.010. eCollection 2017 Sep.

The dynamic plasticity of insulin production in β-cells.

Author information

1
MedImmune, Cardiovascular and Metabolic Disease Research, 1 MedImmune Way, Gaithersburg, MD 20878, USA.

Abstract

BACKGROUND:

Although the insulin-producing pancreatic β-cells are quite capable of adapting to both acute and chronic changes in metabolic demand, persistently high demand for insulin will ultimately lead to their progressive dysfunction and eventual loss. Recent and historical studies highlight the importance of 'resting' the β-cell as a means of preserving functional β-cell mass.

SCOPE OF REVIEW:

We provide experimental evidence to highlight the remarkable plasticity for insulin production and secretion by the pancreatic β-cell alongside some clinical evidence that supports leveraging this unique ability to preserve β-cell function.

MAJOR CONCLUSIONS:

Treatment strategies for type 2 diabetes mellitus (T2DM) targeted towards reducing the systemic metabolic burden, rather than demanding greater insulin production from an already beleaguered β-cell, should be emphasized to maintain endogenous insulin secretory function and delay the progression of T2DM.

KEYWORDS:

ATF6, Activating Transcription Factor 6; CHOP, CCAAT/Enhancer-Binding Homologous Protein; EPAC, Exchange Factor Directly Activated by cAMP; EROβ1, ER-resident oxidoreductase β1; GIP, Gastric Inhibitory Polypeptide; GLP-1, Glucagon-like Peptide 1; GLUT2, Glucose Transporter 2; GSIS, Glucose Stimulated Insulin Secretion; IREα, Inositol Requiring Enzyme α; Insulin production; NEFA, Non-esterified Fatty Acid; PERK, Protein Kinase RNA-like Endoplasmic Reticulum Kinase; PKA, Protein Kinase A; PKC, Protein Kinase C; PLC, Phospholipase C; ROS, Reactive Oxygen Species; SNAP-25, Soluble NSF Attachment Protein 25; SNARE, Soluble NSF Attachment Protein Receptor; STZ, Streptozotocin; T2DM; T2DM, Type 2 Diabetes Mellitus; TRP, Transient Receptor Potential; VAMP-2, Vehicle Associated Membrane Protein 2; VDCC, Voltage Dependent Calcium Channel; mTORC1, Mammalian Target of Rapamycin 1; nH, Hill coefficient; β-cell rest

PMID:
28951821
PMCID:
PMC5605729
DOI:
10.1016/j.molmet.2017.04.010
[Indexed for MEDLINE]
Free PMC Article

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