Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Insulin release from pancreatic beta-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 beta-cells is responsible for Type 1 diabetes (T1D), both lowered beta-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 beta-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-beta to beta-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 beta-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 beta-cell-enriched transcription factors, including FOXO1, PDX1, NKX6.1, MAFA and RFX6, as well as non-coding RNAs, which may contribute to beta-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.

Original publication

DOI

10.1042/BJ20141384

Type

Journal article

Journal

Biochem J

Publication Date

2015

Volume

466

Pages

203 - 218

Keywords

Animals Blood Glucose/metabolism Cell Dedifferentiation Diabetes Mellitus, Type 2/blood/pathology/physiopathology Humans Insulin/*metabolism Insulin Secretion Insulin-Secreting Cells/cytology/*metabolism/pathology Islets of Langerhans/cytology/pathology/physiology/physiopathology Mitochondria/enzymology/metabolism *Models, Biological *Secretory Pathway