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 journalArticle

47 Citations (Scopus)

Abstract

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)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume285
Issue number2 48-2
StatePublished - Aug 1 2003
Externally publishedYes

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Leucine
Chemical activation
KATP Channels
Glucose
Esterification
Palmitates
Glutamine
Citric Acid
Oxidation
Biphasic Insulins
Diazoxide
Glutamate Dehydrogenase
Islets of Langerhans
Rats
Glutamic Acid
Fatty Acids
Adenosine Triphosphate
Insulin
Fluxes

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Activation of the KATPchannel-independent signaling pathway by the nonhydrolyzable analog of leucine, BCH. / Liu, Yi Jia; Cheng, Haiying; Drought, Heather; MacDonald, Michael J.; Sharp, Geoffrey W G; Straub, Susanne G.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 285, No. 2 48-2, 01.08.2003.

Research output: Contribution to journalArticle

Liu, Yi Jia ; Cheng, Haiying ; Drought, Heather ; MacDonald, Michael J. ; Sharp, Geoffrey W G ; Straub, Susanne G. / Activation of the KATPchannel-independent signaling pathway by the nonhydrolyzable analog of leucine, BCH. In: American Journal of Physiology - Endocrinology and Metabolism. 2003 ; Vol. 285, No. 2 48-2.
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