Abstract
Central insulin action in the brain is thought to contribute to metabolic regulation, but the specific hypothalamic nuclei affected in type 2 diabetes (T2D) remain poorly characterized. We performed high-resolution functional MRI (fMRI) during intranasal insulin administration to assess nucleus-level hypothalamic responses in 21 Japanese men with T2D and 20 individuals acting as healthy controls. In controls, insulin rapidly suppressed fMRI signals within 5 minutes in the posterior hypothalamic nucleus; this early suppression was not observed in T2D, indicating impaired hypothalamic insulin responsiveness. In an independent older cohort, structural MRI further revealed decreased gray matter volume in the corresponding posterior hypothalamus in participants with diabetes. These converging functional and structural findings implicate the posterior hypothalamus as a candidate locus associated with brain insulin resistance in T2D, warranting longitudinal and interventional validation.
Authors
Hideyoshi Kaga, Akitoshi Ogawa, Takahiro Osada, Mai Kiya, Satoshi Oka, Yusuke Adachi, Mengping Yu, Shota Sakamoto, Saori Kakehi, Toshiki Kogai, Tsubasa Tajima, Hitoshi Naito, Naoaki Ito, Satoshi Kadowaki, Yuya Nishida, Ryuzo Kawamori, Seiki Konishi, Hirotaka Watada, Yoshifumi Tamura
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