ATP-sensitive K+ channel mediates the zinc switch-off signal for glucagon response during glucose deprivation

Michela Slucca, Jamie S. Harmon, Elizabeth A. Oseid, Joseph Bryan, R. Paul Robertson

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

OBJECTIVE - The intraislet insulin hypothesis proposes that glucagon secretion during hypoglycemia is triggered by a decrease in intraislet insulin secretion. A more recent hypothesis based on in vivo data from hypoglycemic rats is that it is the decrease in zinc cosecreted with insulin from β-cells, rather than the decrease in insulin itself, that signals glucagon secretion from α-cells during hypoglycemia. These studies were designed to determine whether closure of the α-cell ATP-sensitive K+ channel (K ATP channel) is the mechanism through which the zinc switch-off signal triggers glucagon secretion during glucose deprivation. RESEARCH DESIGN AND METHODS - All studies were performed using perifused isolated islets. RESULTS - In control experiments, the expected glucagon response to an endogenous insulin switch-off signal during glucose deprivation was observed in wild-type mouse islets. In experiments with streptozotocin-treated wild-type islets, a glucagon response to an exogenous zinc switch-off signal was observed during glucose deprivation. However, this glucagon response to the zinc switch-off signal during glucose deprivation was not seen in the presence of nifedipine, diazoxide, or tolbutamide or if KATP channel knockout mouse islets were used. All islets had intact glucagon responses to epinephrine. CONCLUSIONS - These data demonstrate that closure of KATP channels and consequent opening of calcium channels is the mechanism through which the zinc switch-off signal triggers glucagon secretion during glucose deprivation.

Original languageEnglish (US)
Pages (from-to)128-134
Number of pages7
JournalDiabetes
Volume59
Issue number1
DOIs
StatePublished - Jan 2010

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