Decreased KATPChannel Activity Contributes to the Low Glucose Threshold for Insulin Secretion of Rat Neonatal Islets
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Decreased KATPChannel Activity Contributes to the Low Glucose Threshold for Insulin Secretion of Rat Neonatal Islets. / Yang, Juxiang; Hammoud, Batoul; Li, Changhong; Ridler, Abigail; Yau, Daphne; Kim, Junil; Won, Kyoung Jae; Stanley, Charles A.; Hoshi, Toshinori; Stanescu, Diana E.
I: Endocrinology, Bind 162, Nr. 9, bqab121, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Decreased KATPChannel Activity Contributes to the Low Glucose Threshold for Insulin Secretion of Rat Neonatal Islets
AU - Yang, Juxiang
AU - Hammoud, Batoul
AU - Li, Changhong
AU - Ridler, Abigail
AU - Yau, Daphne
AU - Kim, Junil
AU - Won, Kyoung Jae
AU - Stanley, Charles A.
AU - Hoshi, Toshinori
AU - Stanescu, Diana E.
N1 - Publisher Copyright: © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2021
Y1 - 2021
N2 - Transitional hypoglycemia in normal newborns occurs in the first 3 days of life and has clinical features consistent with hyperinsulinism. We found a lower threshold for glucose-stimulated insulin secretion from freshly isolated embryonic day (E) 22 rat islets, which persisted into the first postnatal days. The threshold reached the adult level by postnatal day (P) 14. Culturing P14 islets also decreased the glucose threshold. Freshly isolated P1 rat islets had a lower threshold for insulin secretion in response to 2-aminobicyclo-(2, 2, 1)-heptane-2-carboxylic acid, a nonmetabolizable leucine analog, and diminished insulin release in response to tolbutamide, an inhibitor of β-cell KATP channels. These findings suggested that decreased KATP channel function could be responsible for the lower glucose threshold for insulin secretion. Single-cell transcriptomic analysis did not reveal a lower expression of KATP subunit genes in E22 compared with P14 β cells. The investigation of electrophysiological characteristics of dispersed β cells showed that early neonatal and cultured cells had fewer functional KATP channels per unit membrane area. Our findings suggest that decreased surface density of KATP channels may contribute to the observed differences in glucose threshold for insulin release.
AB - Transitional hypoglycemia in normal newborns occurs in the first 3 days of life and has clinical features consistent with hyperinsulinism. We found a lower threshold for glucose-stimulated insulin secretion from freshly isolated embryonic day (E) 22 rat islets, which persisted into the first postnatal days. The threshold reached the adult level by postnatal day (P) 14. Culturing P14 islets also decreased the glucose threshold. Freshly isolated P1 rat islets had a lower threshold for insulin secretion in response to 2-aminobicyclo-(2, 2, 1)-heptane-2-carboxylic acid, a nonmetabolizable leucine analog, and diminished insulin release in response to tolbutamide, an inhibitor of β-cell KATP channels. These findings suggested that decreased KATP channel function could be responsible for the lower glucose threshold for insulin secretion. Single-cell transcriptomic analysis did not reveal a lower expression of KATP subunit genes in E22 compared with P14 β cells. The investigation of electrophysiological characteristics of dispersed β cells showed that early neonatal and cultured cells had fewer functional KATP channels per unit membrane area. Our findings suggest that decreased surface density of KATP channels may contribute to the observed differences in glucose threshold for insulin release.
KW - glucose threshold
KW - hypoglycemia
KW - neonatal
KW - β-cells
U2 - 10.1210/endocr/bqab121
DO - 10.1210/endocr/bqab121
M3 - Journal article
C2 - 34134142
AN - SCOPUS:85111877713
VL - 162
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0013-7227
IS - 9
M1 - bqab121
ER -
ID: 281807566