Glucose-sensing mechanisms in pancreatic β-cells

Author:

MacDonald Patrick E12,Joseph Jamie W3,Rorsman Patrik12

Affiliation:

1. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of OxfordChurchill Hospital, Old Road, Headington, Oxford OX3 7LJ, UK

2. Division of Diabetes, Metabolism and Endocrinology, Lund University221 84 Lund, Sweden

3. Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical CenterDurham, NC 27704, USA

Abstract

The appropriate secretion of insulin from pancreatic β-cells is critically important to the maintenance of energy homeostasis. The β-cells must sense and respond suitably to postprandial increases of blood glucose, and perturbation of glucose-sensing in these cells can lead to hypoglycaemia or hyperglycaemias and ultimately diabetes. Here, we review β-cell glucose-sensing with a particular focus on the regulation of cellular excitability and exocytosis. We examine in turn: (i) the generation of metabolic signalling molecules; (ii) the regulation of β-cell membrane potential; and (iii) insulin granule dynamics and exocytosis. We further discuss the role of well known and putative candidate metabolic signals as regulators of insulin secretion.

Publisher

The Royal Society

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology

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