Involvement of brain ketone bodies and the noradrenergic pathway in diabetic hyperphagia in rats

Kinuyo Iwata, Mika Kinoshita, Shunji Yamada, Takuya Imamura, Yoshihisa Uenoyama, Hiroko Tsukamura, Kei Ichiro Maeda

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)103-113
Number of pages11
JournalJournal of Physiological Sciences
Issue number2
Publication statusPublished - Mar 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology


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