TY - JOUR
T1 - Involvement of brain ketone bodies and the noradrenergic pathway in diabetic hyperphagia in rats
AU - Iwata, Kinuyo
AU - Kinoshita, Mika
AU - Yamada, Shunji
AU - Imamura, Takuya
AU - Uenoyama, Yoshihisa
AU - Tsukamura, Hiroko
AU - Maeda, Kei Ichiro
N1 - Funding Information:
Acknowledgments This work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology (no. 18208025).
PY - 2011/3
Y1 - 2011/3
N2 - Uncontrolled type 1 diabetes leads to hyperphagia and severe ketosis. This study was conducted to test the hypothesis that ketone bodies act on the hindbrain as a starvation signal to induce diabetic hyperphagia. Injection of an inhibitor of monocarboxylate transporter 1, a ketone body transporter, into the fourth ventricle normalized the increase in food intake in streptozotocin (STZ)-induced diabetic rats. Blockade of catecholamine synthesis in the hypothalamic paraventricular nucleus (PVN) also restored food intake to normal levels in diabetic animals. On the other hand, hindbrain injection of the ketone body induced feeding, hyperglycemia, and fatty acid mobilization via increased sympathetic activity and also norepinephrine release in the PVN. This result provides evidence that hyperphagia in STZ-induced type 1 diabetes is signaled by a ketone body sensed in the hindbrain, and mediated by noradrenergic inputs to the PVN.
AB - Uncontrolled type 1 diabetes leads to hyperphagia and severe ketosis. This study was conducted to test the hypothesis that ketone bodies act on the hindbrain as a starvation signal to induce diabetic hyperphagia. Injection of an inhibitor of monocarboxylate transporter 1, a ketone body transporter, into the fourth ventricle normalized the increase in food intake in streptozotocin (STZ)-induced diabetic rats. Blockade of catecholamine synthesis in the hypothalamic paraventricular nucleus (PVN) also restored food intake to normal levels in diabetic animals. On the other hand, hindbrain injection of the ketone body induced feeding, hyperglycemia, and fatty acid mobilization via increased sympathetic activity and also norepinephrine release in the PVN. This result provides evidence that hyperphagia in STZ-induced type 1 diabetes is signaled by a ketone body sensed in the hindbrain, and mediated by noradrenergic inputs to the PVN.
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U2 - 10.1007/s12576-010-0127-6
DO - 10.1007/s12576-010-0127-6
M3 - Article
C2 - 21234734
AN - SCOPUS:79956071578
SN - 1880-6546
VL - 61
SP - 103
EP - 113
JO - Journal of Physiological Sciences
JF - Journal of Physiological Sciences
IS - 2
ER -
