Insulin Treatment Reduces Susceptibility to Atrial Fibrillation in Type 1 Diabetic Mice
Diabetes has been identified as an independent risk factor for atrial fibrillation (AF), the most common chronic cardiac arrhythmia. Whether or not glucose and insulin disturbances observed during diabetes enhance arrhythmogenicity of the atria, potentially leading to AF, is not well-known. We hypot...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-08-01
|
| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcvm.2020.00134/full |
| _version_ | 1828868839895465984 |
|---|---|
| author | Zahra Maria Zahra Maria Allison R. Campolo Allison R. Campolo Benjamin J. Scherlag Jerry W. Ritchey Véronique A. Lacombe Véronique A. Lacombe |
| author_facet | Zahra Maria Zahra Maria Allison R. Campolo Allison R. Campolo Benjamin J. Scherlag Jerry W. Ritchey Véronique A. Lacombe Véronique A. Lacombe |
| author_sort | Zahra Maria |
| collection | DOAJ |
| description | Diabetes has been identified as an independent risk factor for atrial fibrillation (AF), the most common chronic cardiac arrhythmia. Whether or not glucose and insulin disturbances observed during diabetes enhance arrhythmogenicity of the atria, potentially leading to AF, is not well-known. We hypothesized that insulin deficiency and impaired glucose transport provide a metabolic substrate for the development and maintenance of AF during diabetes. Transesophageal atrial pacing was used to induce AF in healthy, streptozotocin-induced insulin-deficient type 1 diabetic, and insulin-treated diabetic mice. Translocation of insulin-sensitive glucose transporters (GLUTs) to the atrial cell surface was measured using a biotinylated photolabeling assay in the perfused heart. Fibrosis and glycogen accumulation in the atrium were measured using histological analysis. Diabetic mice displayed mild hyperglycemia, increased duration and frequency of AF episodes vs. age-matched controls (e.g., AF duration: 19.7 ± 6.8 s vs. 1.8 ± 1.1 s, respectively, p = 0.032), whereas insulin-treated diabetic animals did not. The translocation of insulin-sensitive GLUT-4 and -8 to the atrial cell surface was significantly downregulated in the diabetic mice (by 67 and 79%, respectively; p ≤ 0.001), and rescued by insulin treatment. We did not observe fibrosis or glycogen accumulation in the atria of diabetic mice. Therefore, these data suggest that insulin and glucose disturbances were sufficient to induce AF susceptibility during mild diabetes. |
| first_indexed | 2024-12-13T05:38:36Z |
| format | Article |
| id | doaj.art-388057cf20284b928d8638699379b662 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-13T05:38:36Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-388057cf20284b928d8638699379b6622022-12-21T23:57:50ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2020-08-01710.3389/fcvm.2020.00134488866Insulin Treatment Reduces Susceptibility to Atrial Fibrillation in Type 1 Diabetic MiceZahra Maria0Zahra Maria1Allison R. Campolo2Allison R. Campolo3Benjamin J. Scherlag4Jerry W. Ritchey5Véronique A. Lacombe6Véronique A. Lacombe7Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, United StatesHarold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United StatesDepartment of Physiological Sciences, Oklahoma State University, Stillwater, OK, United StatesHarold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United StatesDepartment of Internal Medicine, University of Oklahoma College of Medicine, Oklahoma City, OK, United StatesDepartment of Veterinary Pathobiology, Oklahoma State University, Stillwater, OK, United StatesDepartment of Physiological Sciences, Oklahoma State University, Stillwater, OK, United StatesHarold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United StatesDiabetes has been identified as an independent risk factor for atrial fibrillation (AF), the most common chronic cardiac arrhythmia. Whether or not glucose and insulin disturbances observed during diabetes enhance arrhythmogenicity of the atria, potentially leading to AF, is not well-known. We hypothesized that insulin deficiency and impaired glucose transport provide a metabolic substrate for the development and maintenance of AF during diabetes. Transesophageal atrial pacing was used to induce AF in healthy, streptozotocin-induced insulin-deficient type 1 diabetic, and insulin-treated diabetic mice. Translocation of insulin-sensitive glucose transporters (GLUTs) to the atrial cell surface was measured using a biotinylated photolabeling assay in the perfused heart. Fibrosis and glycogen accumulation in the atrium were measured using histological analysis. Diabetic mice displayed mild hyperglycemia, increased duration and frequency of AF episodes vs. age-matched controls (e.g., AF duration: 19.7 ± 6.8 s vs. 1.8 ± 1.1 s, respectively, p = 0.032), whereas insulin-treated diabetic animals did not. The translocation of insulin-sensitive GLUT-4 and -8 to the atrial cell surface was significantly downregulated in the diabetic mice (by 67 and 79%, respectively; p ≤ 0.001), and rescued by insulin treatment. We did not observe fibrosis or glycogen accumulation in the atria of diabetic mice. Therefore, these data suggest that insulin and glucose disturbances were sufficient to induce AF susceptibility during mild diabetes.https://www.frontiersin.org/article/10.3389/fcvm.2020.00134/fullglucose transportersarrhythmiasglycogenmetabolismdiabetesatria |
| spellingShingle | Zahra Maria Zahra Maria Allison R. Campolo Allison R. Campolo Benjamin J. Scherlag Jerry W. Ritchey Véronique A. Lacombe Véronique A. Lacombe Insulin Treatment Reduces Susceptibility to Atrial Fibrillation in Type 1 Diabetic Mice Frontiers in Cardiovascular Medicine glucose transporters arrhythmias glycogen metabolism diabetes atria |
| title | Insulin Treatment Reduces Susceptibility to Atrial Fibrillation in Type 1 Diabetic Mice |
| title_full | Insulin Treatment Reduces Susceptibility to Atrial Fibrillation in Type 1 Diabetic Mice |
| title_fullStr | Insulin Treatment Reduces Susceptibility to Atrial Fibrillation in Type 1 Diabetic Mice |
| title_full_unstemmed | Insulin Treatment Reduces Susceptibility to Atrial Fibrillation in Type 1 Diabetic Mice |
| title_short | Insulin Treatment Reduces Susceptibility to Atrial Fibrillation in Type 1 Diabetic Mice |
| title_sort | insulin treatment reduces susceptibility to atrial fibrillation in type 1 diabetic mice |
| topic | glucose transporters arrhythmias glycogen metabolism diabetes atria |
| url | https://www.frontiersin.org/article/10.3389/fcvm.2020.00134/full |
| work_keys_str_mv | AT zahramaria insulintreatmentreducessusceptibilitytoatrialfibrillationintype1diabeticmice AT zahramaria insulintreatmentreducessusceptibilitytoatrialfibrillationintype1diabeticmice AT allisonrcampolo insulintreatmentreducessusceptibilitytoatrialfibrillationintype1diabeticmice AT allisonrcampolo insulintreatmentreducessusceptibilitytoatrialfibrillationintype1diabeticmice AT benjaminjscherlag insulintreatmentreducessusceptibilitytoatrialfibrillationintype1diabeticmice AT jerrywritchey insulintreatmentreducessusceptibilitytoatrialfibrillationintype1diabeticmice AT veroniquealacombe insulintreatmentreducessusceptibilitytoatrialfibrillationintype1diabeticmice AT veroniquealacombe insulintreatmentreducessusceptibilitytoatrialfibrillationintype1diabeticmice |