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Updated: May 12, 2026
04:41
Glucose-Stimulated Insulin Secretion via Perfusion through the Mice Vasculature with an Intact Pancreas
Published on: July 25, 2025
Cephalic phase insulin secretion is KATP channel independent
Yusuke Seino1, Takashi Miki, Wakako Fujimoto
1Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
The Journal of Endocrinology
|April 24, 2013
Summary
Vagal nerve activity, independent of ATP-sensitive potassium (KATP) channels, plays a key role in nutrient-stimulated insulin secretion. This discovery offers new insights into glucose homeostasis and metabolic regulation.
Area of Science:
- Physiology
- Endocrinology
- Neuroscience
Background:
- Insulin secretion is vital for glucose homeostasis.
- ATP-sensitive potassium (KATP) channels in pancreatic β-cells are crucial for glucose-induced insulin release.
- Mice lacking Kir6.2, the KATP channel pore subunit, exhibit impaired insulin secretion in vitro.
Purpose of the Study:
- To investigate the role of KATP channel-independent mechanisms in nutrient-stimulated insulin secretion in vivo.
- To compare insulin secretion via voluntary versus forced feeding in wild-type and Kir6.2 knockout mice.
- To elucidate the involvement of the vagal nerve in nutrient-induced insulin release.
Main Methods:
- Comparison of insulin secretion in Kir6.2(+/+) and Kir6.2(-/-) mice under voluntary and forced feeding conditions.
- Administration of atropine methyl nitrate to block muscarinic receptors.
- Pancreas perfusion studies with and without carbamylcholine.
Main Results:
- Similar blood glucose and plasma insulin levels in both genotypes under ad libitum feeding.
- Voluntary carbohydrate feeding induced insulin secretion in Kir6.2(-/-) mice, albeit attenuated compared to wild-type.
- Forced feeding markedly impaired or abolished insulin secretion in Kir6.2(-/-) mice.
- Atropine methyl nitrate pretreatment blocked voluntary feeding-induced insulin secretion in Kir6.2(-/-) mice.
- Carbamylcholine restored glucose-induced insulin secretion in perfused pancreases from Kir6.2(-/-) mice.
Conclusions:
- A KATP channel-independent pathway, mediated by vagal nerve signaling, is critical for nutrient-stimulated insulin secretion in vivo.
- Vagal nerve activation can trigger insulin release independently of direct nutrient sensing by β-cell KATP channels.
- These findings highlight the complex interplay between neural and metabolic regulation of insulin secretion.
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