Control of pancreatic β cell regeneration by glucose metabolism

Cell Metab. 2011 Apr 6;13(4):440-449. doi: 10.1016/j.cmet.2011.02.012.


Recent studies revealed a surprising regenerative capacity of insulin-producing β cells in mice, suggesting that regenerative therapy for human diabetes could in principle be achieved. Physiologic β cell regeneration under stressed conditions relies on accelerated proliferation of surviving β cells, but the factors that trigger and control this response remain unclear. Using islet transplantation experiments, we show that β cell mass is controlled systemically rather than by local factors such as tissue damage. Chronic changes in β cell glucose metabolism, rather than blood glucose levels per se, are the main positive regulator of basal and compensatory β cell proliferation in vivo. Intracellularly, genetic and pharmacologic manipulations reveal that glucose induces β cell replication via metabolism by glucokinase, the first step of glycolysis, followed by closure of K(ATP) channels and membrane depolarization. Our data provide a molecular mechanism for homeostatic control of β cell mass by metabolic demand.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism*
  • Cell Membrane / physiology
  • Cell Proliferation
  • Glucokinase / antagonists & inhibitors
  • Glucokinase / metabolism
  • Glycolysis
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / physiology*
  • Insulin-Secreting Cells / transplantation
  • KATP Channels / metabolism
  • Mice
  • Regeneration*


  • Blood Glucose
  • KATP Channels
  • Glucokinase