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Diabetes Obes Metab. 2016 Sep;18 Suppl 1:78-86. doi: 10.1111/dom.12729.

Mechanisms of β-cell functional adaptation to changes in workload.

Author information

1
Departments of Pediatrics and Cellular and Molecular Medicine, Pediatric Diabetes Research Center, University of California San Diego, La Jolla.
2
Departments of Pediatrics and Cellular and Molecular Medicine, Pediatric Diabetes Research Center, University of California San Diego, La Jolla. masander@ucsd.edu.

Abstract

Insulin secretion must be tightly coupled to nutritional state to maintain blood glucose homeostasis. To this end, pancreatic β-cells sense and respond to changes in metabolic conditions, thereby anticipating insulin demands for a given physiological context. This is achieved in part through adjustments of nutrient metabolism, which is controlled at several levels including allosteric regulation, post-translational modifications, and altered expression of metabolic enzymes. In this review, we discuss mechanisms of β-cell metabolic and functional adaptation in the context of two physiological states that alter glucose-stimulated insulin secretion: fasting and insulin resistance. We review current knowledge of metabolic changes that occur in the β-cell during adaptation and specifically discuss transcriptional mechanisms that underlie β-cell adaptation. A more comprehensive understanding of how β-cells adapt to changes in nutrient state could identify mechanisms to be co-opted for therapeutically modulating insulin secretion in metabolic disease.

KEYWORDS:

adaptation; fasting; insulin resistance; insulin secretion; metabolism; transcription; β-cell

PMID:
27615135
PMCID:
PMC5021190
[Available on 2017-09-01]
DOI:
10.1111/dom.12729
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