TALK-1-mediated alterations of β-cell mitochondrial function and insulin secretion impair glucose homeostasis on a diabetogenic diet
Summary: Mitochondrial Ca2+ ([Ca2+]m) homeostasis is critical for β-cell function and becomes disrupted during the pathogenesis of diabetes. [Ca2+]m uptake is dependent on elevations in cytoplasmic Ca2+ ([Ca2+]c) and endoplasmic reticulum Ca2+ ([Ca2+]ER) release, both of which are regulated by the t...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724000019 |
| _version_ | 1797357798803111936 |
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| author | Sarah M. Graff Arya Y. Nakhe Prasanna K. Dadi Matthew T. Dickerson Jordyn R. Dobson Karolina E. Zaborska Chloe E. Ibsen Regan B. Butterworth Nicholas C. Vierra David A. Jacobson |
| author_facet | Sarah M. Graff Arya Y. Nakhe Prasanna K. Dadi Matthew T. Dickerson Jordyn R. Dobson Karolina E. Zaborska Chloe E. Ibsen Regan B. Butterworth Nicholas C. Vierra David A. Jacobson |
| author_sort | Sarah M. Graff |
| collection | DOAJ |
| description | Summary: Mitochondrial Ca2+ ([Ca2+]m) homeostasis is critical for β-cell function and becomes disrupted during the pathogenesis of diabetes. [Ca2+]m uptake is dependent on elevations in cytoplasmic Ca2+ ([Ca2+]c) and endoplasmic reticulum Ca2+ ([Ca2+]ER) release, both of which are regulated by the two-pore domain K+ channel TALK-1. Here, utilizing a novel β-cell TALK-1-knockout (β-TALK-1-KO) mouse model, we found that TALK-1 limited β-cell [Ca2+]m accumulation and ATP production. However, following exposure to a high-fat diet (HFD), ATP-linked respiration, glucose-stimulated oxygen consumption rate, and glucose-stimulated insulin secretion (GSIS) were increased in control but not TALK1-KO mice. Although β-TALK-1-KO animals showed similar GSIS before and after HFD treatment, these mice were protected from HFD-induced glucose intolerance. Collectively, these data identify that TALK-1 channel control of β-cell function reduces [Ca2+]m and suggest that metabolic remodeling in diabetes drives dysglycemia. |
| first_indexed | 2024-03-08T14:50:25Z |
| format | Article |
| id | doaj.art-bafc4693a1fb4df690f3a63ad1e180e7 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-08T14:50:25Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-bafc4693a1fb4df690f3a63ad1e180e72024-01-11T04:31:17ZengElsevierCell Reports2211-12472024-01-01431113673TALK-1-mediated alterations of β-cell mitochondrial function and insulin secretion impair glucose homeostasis on a diabetogenic dietSarah M. Graff0Arya Y. Nakhe1Prasanna K. Dadi2Matthew T. Dickerson3Jordyn R. Dobson4Karolina E. Zaborska5Chloe E. Ibsen6Regan B. Butterworth7Nicholas C. Vierra8David A. Jacobson9Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA; Department of Pharmacy and Pharmaceutical Sciences, Lipscomb University, Nashville, TN 37204, USADepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USADepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USADepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USADepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USADepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USADepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USADepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USADepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USADepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA; Corresponding authorSummary: Mitochondrial Ca2+ ([Ca2+]m) homeostasis is critical for β-cell function and becomes disrupted during the pathogenesis of diabetes. [Ca2+]m uptake is dependent on elevations in cytoplasmic Ca2+ ([Ca2+]c) and endoplasmic reticulum Ca2+ ([Ca2+]ER) release, both of which are regulated by the two-pore domain K+ channel TALK-1. Here, utilizing a novel β-cell TALK-1-knockout (β-TALK-1-KO) mouse model, we found that TALK-1 limited β-cell [Ca2+]m accumulation and ATP production. However, following exposure to a high-fat diet (HFD), ATP-linked respiration, glucose-stimulated oxygen consumption rate, and glucose-stimulated insulin secretion (GSIS) were increased in control but not TALK1-KO mice. Although β-TALK-1-KO animals showed similar GSIS before and after HFD treatment, these mice were protected from HFD-induced glucose intolerance. Collectively, these data identify that TALK-1 channel control of β-cell function reduces [Ca2+]m and suggest that metabolic remodeling in diabetes drives dysglycemia.http://www.sciencedirect.com/science/article/pii/S2211124724000019CP: MetabolismCP: Cell biology |
| spellingShingle | Sarah M. Graff Arya Y. Nakhe Prasanna K. Dadi Matthew T. Dickerson Jordyn R. Dobson Karolina E. Zaborska Chloe E. Ibsen Regan B. Butterworth Nicholas C. Vierra David A. Jacobson TALK-1-mediated alterations of β-cell mitochondrial function and insulin secretion impair glucose homeostasis on a diabetogenic diet Cell Reports CP: Metabolism CP: Cell biology |
| title | TALK-1-mediated alterations of β-cell mitochondrial function and insulin secretion impair glucose homeostasis on a diabetogenic diet |
| title_full | TALK-1-mediated alterations of β-cell mitochondrial function and insulin secretion impair glucose homeostasis on a diabetogenic diet |
| title_fullStr | TALK-1-mediated alterations of β-cell mitochondrial function and insulin secretion impair glucose homeostasis on a diabetogenic diet |
| title_full_unstemmed | TALK-1-mediated alterations of β-cell mitochondrial function and insulin secretion impair glucose homeostasis on a diabetogenic diet |
| title_short | TALK-1-mediated alterations of β-cell mitochondrial function and insulin secretion impair glucose homeostasis on a diabetogenic diet |
| title_sort | talk 1 mediated alterations of β cell mitochondrial function and insulin secretion impair glucose homeostasis on a diabetogenic diet |
| topic | CP: Metabolism CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724000019 |
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