Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production.
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Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production. / Könner, A Christine; Janoschek, Ruth; Plum, Leona; Jordan, Sabine; Rother, Eva; Ma, Xiaosong; Xu, Chun; Enriori, Pablo; Hampel, Brigitte; Barsh, Gregory S; Kahn, C Ronald; Cowley, Michael A; Ashcroft, Frances M; Brüning, Jens C.
In: CELL METAB, Vol. 5, No. 6, 6, 2007, p. 438-449.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production.
AU - Könner, A Christine
AU - Janoschek, Ruth
AU - Plum, Leona
AU - Jordan, Sabine
AU - Rother, Eva
AU - Ma, Xiaosong
AU - Xu, Chun
AU - Enriori, Pablo
AU - Hampel, Brigitte
AU - Barsh, Gregory S
AU - Kahn, C Ronald
AU - Cowley, Michael A
AU - Ashcroft, Frances M
AU - Brüning, Jens C
PY - 2007
Y1 - 2007
N2 - Insulin action in the central nervous system regulates energy homeostasis and glucose metabolism. To define the insulin-responsive neurons that mediate these effects, we generated mice with selective inactivation of the insulin receptor (IR) in either pro-opiomelanocortin (POMC)- or agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus. While neither POMC- nor AgRP-restricted IR knockout mice exhibited altered energy homeostasis, insulin failed to normally suppress hepatic glucose production during euglycemic-hyperinsulinemic clamps in AgRP-IR knockout (IR(DeltaAgRP)) mice. These mice also exhibited reduced insulin-stimulated hepatic interleukin-6 expression and increased hepatic expression of glucose-6-phosphatase. These results directly demonstrate that insulin action in POMC and AgRP cells is not required for steady-state regulation of food intake and body weight. However, insulin action specifically in AgRP-expressing neurons does play a critical role in controlling hepatic glucose production and may provide a target for the treatment of insulin resistance in type 2 diabetes.
AB - Insulin action in the central nervous system regulates energy homeostasis and glucose metabolism. To define the insulin-responsive neurons that mediate these effects, we generated mice with selective inactivation of the insulin receptor (IR) in either pro-opiomelanocortin (POMC)- or agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus. While neither POMC- nor AgRP-restricted IR knockout mice exhibited altered energy homeostasis, insulin failed to normally suppress hepatic glucose production during euglycemic-hyperinsulinemic clamps in AgRP-IR knockout (IR(DeltaAgRP)) mice. These mice also exhibited reduced insulin-stimulated hepatic interleukin-6 expression and increased hepatic expression of glucose-6-phosphatase. These results directly demonstrate that insulin action in POMC and AgRP cells is not required for steady-state regulation of food intake and body weight. However, insulin action specifically in AgRP-expressing neurons does play a critical role in controlling hepatic glucose production and may provide a target for the treatment of insulin resistance in type 2 diabetes.
M3 - SCORING: Zeitschriftenaufsatz
VL - 5
SP - 438
EP - 449
JO - CELL METAB
JF - CELL METAB
SN - 1550-4131
IS - 6
M1 - 6
ER -
