Pancreatic β-cell identity, glucose sensing and the control of insulin secretion

Guy A Rutter, Timothy J Pullen, David J Hodson, Aida Martinez-Sanchez

Research output: Contribution to journalArticlepeer-review

192 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)203-18
Number of pages16
JournalBiochemical Journal
Issue number2
Publication statusPublished - 1 Mar 2015


  • Animals
  • Blood Glucose
  • Cell Dedifferentiation
  • Diabetes Mellitus, Type 2
  • Humans
  • Insulin
  • Insulin-Secreting Cells
  • Islets of Langerhans
  • Mitochondria
  • Models, Biological
  • Secretory Pathway


Dive into the research topics of 'Pancreatic β-cell identity, glucose sensing and the control of insulin secretion'. Together they form a unique fingerprint.

Cite this