RT Journal Article
SR Electronic
T1 Zinc, Not Insulin, Regulates the Rat α-Cell Response to Hypoglycemia In Vivo
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 1107
OP 1112
DO 10.2337/db06-1454
VO 56
IS 4
A1 Zhou, Huarong
A1 Zhang, Tao
A1 Harmon, Jamie S.
A1 Bryan, Joseph
A1 Robertson, R. Paul
YR 2007
UL http://diabetes.diabetesjournals.org/content/56/4/1107.abstract
AB The intraislet insulin hypothesis proposes that the decrement in β-cell insulin secretion during hypoglycemia provides an activation signal for α-cells to release glucagon. A more recent hypothesis proposes that zinc atoms suppress glucagon secretion via their ability to open α-cell ATP-sensitive K+ channels. Since insulin binds zinc, and zinc is cosecreted with insulin, we tested whether decreased zinc delivery to the α-cell activates glucagon secretion. In streptozotocin-induced diabetic Wistar rats, we observed that switching off intrapancreatic artery insulin infusions in vivo during hypoglycemia greatly improved glucagon secretion (area under the curve [AUC]: control group 240 ± 261 and experimental group 4,346 ± 1,259 pg · ml−1 · 90 min−1; n = 5, P < 0.02). Switching off pancreatic artery infusions of zinc chloride during hypoglycemia also improved the glucagon response (AUC: control group 817 ± 107 and experimental group 3,445 ± 573 pg · ml−1 · 90 min−1; n = 6, P < 0.01). However, switching off zinc-free insulin infusions had no effect. Studies of glucose uptake in muscle and liver cell lines verified that the zinc-free insulin was biologically active. We conclude that zinc atoms, not the insulin molecule itself, provide the switch-off signal from the β-cell to the α-cell to initiate glucagon secretion during hypoglycemia.