Activation of the KATPchannel-independent signaling pathway by the nonhydrolyzable analog of leucine, BCH

Yi Jia Liu, Haiying Cheng, Heather Drought, Michael J. MacDonald, Geoffrey W.G. Sharp, Susanne G. Straub

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Leucine and giutamine were used to elicit biphasic insulin release in rat pancreatic islets. Leucine did not mimic the full biphasic response of glucose. Glutamine was without effect. However, the combination of the two did mimic the biphasic response. When the ATP-sensitive K+ (KATP) channel-independent pathway was studied in the presence of diazoxide and KCl, leucine and its nonmetabolizable analog 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH) both stimulated insulin secretion to a greater extent than glucose. Glutamine and dimethyl glutamate had no effect. Because the only known action of BCH is stimulation of glutamate dehydrogenase, this is sufficient to develop the full effect of the KATP channel-independent pathway. Glucose, leucine, and BCH had no effect on intracellular citrate levels. Leucine and BCH both decreased glutamate levels, whereas glucose was without effect. Glucose and leucine decreased palmitate oxidation and increased esterification. Strikingly, BCH had no effect on palmitate oxidation or esterification. Thus BCH activates the KATP channel-independent pathway of glucose signaling without raising citrate levels, without decreasing fatty acid oxidation, and without mimicking the effects of glucose and leucine on esterification. The results indicate that increased flux through the TCA cycle is sufficient to activate the KATP channel-independent pathway.

Original languageEnglish (US)
Pages (from-to)E380-E389
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number2 48-2
StatePublished - Aug 1 2003
Externally publishedYes


  • 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid
  • ATP-sensitive K channel

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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