Alpha cell receptor for advanced glycation end products associate with glucagon expression in type 1 diabetes.
Alpha cell receptor for advanced glycation end products associate with glucagon expression in type 1 diabetes.
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DOI：
10.1038/s41598-023-39243-x
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发表时间：
2023-08-09
影响因子：
4.6
通讯作者：
Forbes, Josephine M.
中科院分区：
文献类型：
--
作者：
Leung, Sherman S.;Lenchik, Nataliya;Mathews, Clayton;Pugliese, Alberto;McCarthy, Domenica A.;Le Bagge, Selena;Ewing, Adam;Harris, Mark;Radford, Kristen J.;Borg, Danielle J.;Gerling, Ivan;Forbes, Josephine M.
Hypoglycemia in type 1 diabetes associates with changes in the pancreatic islet α cells, where the receptor for advanced glycation end products (RAGE) is highly expressed. This study compared islet RAGE expression in donors without diabetes, those at risk of, and those with type 1 diabetes. Laser-dissected islets were subject to RNA bioinformatics and adjacent pancreatic tissue were assessed by confocal microscopy. We found that islets from type 1 diabetes donors had differential expression of the RAGE gene (AGER) and its correlated genes, based on glucagon expression. Random forest machine learning revealed that AGER was the most important predictor for islet glucagon levels. Conversely, a generalized linear model identified that glucagon expression could be predicted by expression of RAGE signaling molecules, its ligands and enzymes that create or clear RAGE ligands. Confocal imaging co-localized RAGE, its ligands and signaling molecules to the α cells. Half of the type 1 diabetes cohort comprised of adolescents and a patient with history of hypoglycemia—all showed an inverse relationship between glucagon and RAGE. These data confirm an association between glucagon and islet RAGE, its ligands and signaling pathways in type 1 diabetes, which warrants functional investigation into a role for RAGE in hypoglycemia.
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影响因子：
7.7
作者：
Coughlan MT;Yap FY;Tong DC;Andrikopoulos S;Gasser A;Thallas-Bonke V;Webster DE;Miyazaki J;Kay TW;Slattery RM;Kaye DM;Drew BG;Kingwell BA;Fourlanos S;Groop PH;Harrison LC;Knip M;Forbes JM
通讯作者：
Forbes JM
影响因子：
14.8
作者：
Durruthy-Durruthy R;Gottlieb A;Heller S
通讯作者：
Heller S
影响因子：
7.7
作者：
Lam, Carol J.;Cox, Aaron R.;Kushner, Jake A.
通讯作者：
Kushner, Jake A.
影响因子：
8.2
作者：
Forbes, J. M.;Soderlund, J.;Groop, P. -H.
通讯作者：
Groop, P. -H.
影响因子：
7.7
作者：
Hope, KM;Tran, POT;Robertson, RP
通讯作者：
Robertson, RP