Article ; Online: TRPM7 kinase is required for insulin production and compensatory islet responses during obesity.
JCI insight
2023 Volume 8, Issue 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 transient ... ...
| 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 transient receptor potential cation channel subfamily M member 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 disrupted insulin secretion and led to progressive glucose intolerance. We indicate that the diminished insulinotropic response in β cell-specific Trpm7-knockout mice was caused by decreased insulin production because of impaired enzymatic activity of this protein. Accordingly, high-fat-fed mice with a genetic loss of TRPM7 kinase activity displayed a marked glucose intolerance accompanied by hyperglycemia. These detrimental glucoregulatory effects were engendered by reduced compensatory β cell responses because of mitigated protein kinase B (AKT)/ERK signaling. Collectively, our data identify TRPM7 kinase as a potentially novel regulator of insulin synthesis, β cell dynamics, and glucose homeostasis under obesogenic diet. |
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| MeSH term(s) | Animals ; Mice ; Glucose ; Glucose Intolerance ; Insulin/metabolism ; Mice, Knockout ; Obesity ; Protein Serine-Threonine Kinases/metabolism ; TRPM Cation Channels/genetics ; TRPM Cation Channels/metabolism |
| Chemical Substances | Glucose (IY9XDZ35W2) ; Insulin ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; TRPM Cation Channels ; Trpm7 protein, mouse (EC 2.7.1.-) |
| Language | English |
| Publishing date | 2023-02-08 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ISSN | 2379-3708 |
| ISSN (online) | 2379-3708 |
| DOI | 10.1172/jci.insight.163397 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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