ATP-Sensitive K+ Channel Mediates the Zinc Switch-0ff Signal for Glucagon Response During Glucose Deprivation

Slucca, Michela; Harmon, Jamie S.; Oseid, Elizabeth A.; Bryan, Joseph; Robertson, R. Paul
January 2010
Diabetes;Jan2010, Vol. 59 Issue 1, p128
Academic Journal
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[sup +] channel (KATP 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 K[sub ATP] channel knockout mouse islets were used. All islets had intact glucagon responses to epinephrine. CONCLUSIONS--These data demonstrate that closure of K[sub ATP] channels and consequent opening of calcium channels is the mechanism through which the zinc switch-off signal triggers glucagon secretion during glucose deprivation. Diabetes 59: 128-134, 2010


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