Mechanisms by which glucose can control insulin release independently from its action on adenosine triphosphate-sensitive K+ channels in mouse B cells

J Clin Invest. 1993 Mar;91(3):871-80. doi: 10.1172/JCI116308.


Glucose stimulation of insulin release involves closure of ATP-sensitive K+ channels (K(+)-ATP channels), depolarization, and Ca2+ influx in B cells. However, by using diazoxide to open K(+)-ATP channels, and 30 mM K to depolarize the membrane, we could demonstrate that another mechanism exists, by which glucose can control insulin release independently from changes in K(+)-ATP channel activity and in membrane potential (Gembal et al. 1992. J. Clin. Invest. 89:1288-1295). A similar approach was followed here to investigate, with mouse islets, the nature of this newly identified mechanism. The membrane potential-independent increase in insulin release produced by glucose required metabolism of the sugar and was mimicked by other metabolized secretagogues. It also required elevated levels of cytoplasmic Cai2+, but was not due to further changes in Cai2+. It could not be ascribed to acceleration of phosphoinositide metabolism, or to activation of protein kinases A or C. Thus, glucose did not increase inositol phosphate levels and hardly affected cAMP levels. Moreover, increasing inositol phosphates by vasopressin or cAMP by forskolin, and activating protein kinase C by phorbol esters did not mimic the action of glucose on release, and down-regulation of protein kinase C did not prevent these effects. On the other hand, it correlated with an increase in the ATP/ADP ratio in islet cells. We suggest that the membrane potential-independent control of insulin release exerted by glucose involves changes in the energy state of B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphate / metabolism*
  • Animals
  • Cells, Cultured
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Diazoxide / pharmacology
  • Diterpenes*
  • Glucose / pharmacology*
  • Inositol Phosphates / metabolism
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Keto Acids / pharmacology
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred Strains
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Potassium / pharmacology
  • Potassium Channels / drug effects
  • Potassium Channels / physiology*
  • Protein Kinase C / metabolism
  • Terpenes / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology


  • Diterpenes
  • Inositol Phosphates
  • Insulin
  • Keto Acids
  • Potassium Channels
  • Terpenes
  • Colforsin
  • mezerein
  • Phorbol 12,13-Dibutyrate
  • Adenosine Diphosphate
  • alpha-ketoisocaproic acid
  • Adenosine Triphosphate
  • Cyclic AMP
  • Protein Kinase C
  • Glucose
  • Tetradecanoylphorbol Acetate
  • Diazoxide
  • Potassium