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- Title
Pancreatic β-cell identity, glucose sensing and the control of insulin secretion.
- Authors
Rutter, Guy A.; Pullen, Timothy J.; Hodson, David J.; Martinez-Sanchez, Aida
- Abstract
Insulin release from pancreatic β-cells is required to maintain normal glucose homoeostasis in man and many other animals. Defective insulin secretion underlies all forms of diabetes mellitus, a disease currently reaching epidemic proportions worldwide. Although the destruction of β-cells is responsible for Type 1 diabetes (T1D), both lowered β-cell mass and loss of secretory function are implicated in Type 2 diabetes (T2D). Emerging results suggest that a functional deficiency, involving de-differentiation of the mature β-cell towards a more progenitor-like state, may be an important driver for impaired secretion in T2D. Conversely, at least in rodents, reprogramming of islet non-β to β-cells appears to occur spontaneously in models of T1D, and may occur in man. In the present paper, we summarize the biochemical properties which define the 'identity' of the mature β-cell as a glucose sensor par excellence. In particular, we discuss the importance of suppressing a group of 11 'disallowed' housekeeping genes, including Ldha and the monocarboxylate transporter Mct1 (Slc16a1), for normal nutrient sensing. We then survey the changes in the expression and/or activity of β-cell-enriched transcription factors, including FOXO1, PDX1, NKX6.1, MAFA and RFX6, as well as non-coding RNAs, which may contribute to β-cell de-differentiation and functional impairment in T2D. The relevance of these observations for the development of new approaches to treat T1D and T2D is considered.
- Subjects
TREATMENT of diabetes; PANCREATIC beta cells; TYPE 1 diabetes; GLUCOSE analysis; GENE expression; GENETIC transcription; INSULIN resistance; ELECTROPHYSIOLOGY; GENETICS
- Publication
Biochemical Journal, 2015, Vol 466, Issue 2, p203
- ISSN
0264-6021
- Publication type
Academic Journal
- DOI
10.1042/BJ20141384