Mechanisms of β-cell functional adaptation to changes in workload.
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.
Departments of Pediatrics and Cellular and Molecular Medicine, Pediatric Diabetes Research Center, University of California San Diego, La Jolla.
M
M
Wortham
Departments of Pediatrics and Cellular and Molecular Medicine, Pediatric Diabetes Research Center, University of California San Diego, La Jolla. masander@ucsd.edu.
M
M
Sander
D000222:Adaptation, Physiological; D000494:Allosteric Regulation; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
D001786:Blood Glucose; D007328:Insulin
adaptation; fasting; insulin resistance; insulin secretion; metabolism; transcription; β-cell