TY - JOUR
T1 - Preferential Gq signaling in diabetes
T2 - An electrical switch in incretin action and in diabetes progression?
AU - Nichols, Colin G.
AU - York, Nathaniel W.
AU - Remedi, Maria S.
N1 - Publisher Copyright:
© 2020, American Society for Clinical Investigation.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Patients with type 2 diabetes (T2D) fail to secrete insulin in response to increased glucose levels that occur with eating. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are two incretins secreted from gastrointestinal cells that amplify insulin secretion when glucose is high. In this issue of the JCI, Oduori et al. explore the role of ATP-sensitive K+ (KATP) channels in maintaining glucose homeostasis. In persistently depolarized β cells from KATP channel knockout (KO) mice, the researchers revealed a shift in G protein signaling from the Gs family to the Gq family. This shift explains why GLP-1, which signals via Gq, but not GIP, which signals preferentially via Gs, can effectively potentiate secretion in islets from the KATP channel–deficient mice and in other models of KATP deficiency, including diabetic KK-Ay mice. Their results provide one explanation for differential insulinotropic potential of incretins in human T2D and point to a potentially unifying model for T2D progression itself.
AB - Patients with type 2 diabetes (T2D) fail to secrete insulin in response to increased glucose levels that occur with eating. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are two incretins secreted from gastrointestinal cells that amplify insulin secretion when glucose is high. In this issue of the JCI, Oduori et al. explore the role of ATP-sensitive K+ (KATP) channels in maintaining glucose homeostasis. In persistently depolarized β cells from KATP channel knockout (KO) mice, the researchers revealed a shift in G protein signaling from the Gs family to the Gq family. This shift explains why GLP-1, which signals via Gq, but not GIP, which signals preferentially via Gs, can effectively potentiate secretion in islets from the KATP channel–deficient mice and in other models of KATP deficiency, including diabetic KK-Ay mice. Their results provide one explanation for differential insulinotropic potential of incretins in human T2D and point to a potentially unifying model for T2D progression itself.
UR - http://www.scopus.com/inward/record.url?scp=85097112513&partnerID=8YFLogxK
U2 - 10.1172/JCI143199
DO - 10.1172/JCI143199
M3 - Review article
C2 - 33196460
AN - SCOPUS:85097112513
SN - 0021-9738
VL - 130
SP - 6235
EP - 6237
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 12
ER -