TRPM7 kinase is required for insulin production and compensatory islet responses during obesity

Khajavi, Noushafarin; Beck, Andreas; Ricku, Klea; Beyerle, Philipp; Jacob, Katharina; Syamsul, Sabrina F.; Belkacemi, Anouar; Reinach, Peter S.; Schreier, Pascale C.F.; Salah, Houssein; Popp, Tanja; Novikoff, Aaron; Breit, Andreas; Chubanov, Vladimir; Müller, Timo D.; Zierler, Susanna und Gudermann, Thomas (2023): TRPM7 kinase is required for insulin production and compensatory islet responses during obesity. In: JCI Insight, Vol. 8, No. 3

Abstract

Most overweight individuals do not develop diabetes due to compensatory islet responses to restore glucose homeostasis. Therefore, regulatory pathways that promote β-cell compensation are potential targets for treatment of diabetes. The melastatin transient receptor potential 7 protein (TRPM7), harboring a cation channel and a serine/threonine kinase, has been implicated in controlling cell growth and proliferation. Here, we report that selective deletion of Trpm7 in β-cells disrupts insulin secretion and leads to progressive glucose intolerance. We indicate that the diminished insulinotropic response in β-cell-specific Trpm7 knockout mice is caused by decreased insulin production due to an impaired enzymatic activity of this protein. Accordingly, high-fat fed mice with a genetic loss of TRPM7 kinase activity (Trpm7R/R) display a marked glucose intolerance accompanied by hyperglycemia. These detrimental glucoregulatory effects are engendered by reduced compensatory β-cell responses due to mitigated AKT/ERK signaling. Collectively, our data identify TRPM7 kinase as a novel regulator of insulin synthesis, β-cell dynamics, and glucose homeostasis under obesogenic diet.

• Item Type: Journal article
• Faculties: Medicine > Walther Straub Institute of Pharmacology and toxicology
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 2379-3708
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 239283807
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892