Relationships between mitochondrial function and metabolic flexibility in type 2 diabetes mellitus.
INTRODUCTION: Mitochondrial dysfunction, lipid accumulation, insulin resistance and metabolic inflexibility have been implicated in the etiology of type 2 diabetes (T2D), yet their interrelationship remains speculative. We investigated these interrelationships in a group of T2D and obese normoglycem...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3572106?pdf=render |
| _version_ | 1828388657698963456 |
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| author | Tineke van de Weijer Lauren Marie Sparks Esther Phielix Ruth Carla Meex Noud Antonius van Herpen Matthijs Karel C Hesselink Patrick Schrauwen Vera Bettina Schrauwen-Hinderling |
| author_facet | Tineke van de Weijer Lauren Marie Sparks Esther Phielix Ruth Carla Meex Noud Antonius van Herpen Matthijs Karel C Hesselink Patrick Schrauwen Vera Bettina Schrauwen-Hinderling |
| author_sort | Tineke van de Weijer |
| collection | DOAJ |
| description | INTRODUCTION: Mitochondrial dysfunction, lipid accumulation, insulin resistance and metabolic inflexibility have been implicated in the etiology of type 2 diabetes (T2D), yet their interrelationship remains speculative. We investigated these interrelationships in a group of T2D and obese normoglycemic control subjects. METHODS: 49 non-insulin dependent male T2D patients and 54 male control subjects were enrolled, and a hyperinsulinemic-euglycemic clamp and indirect calorimetry were performed. A muscle biopsy was taken and intramyocellular lipid (IMCL) was measured. In vivo mitochondrial function was measured by PCr recovery in 30 T2D patients and 31 control subjects. RESULTS: Fasting NEFA levels were significantly elevated in T2D patients compared with controls, but IMCL was not different. Mitochondrial function in T2D patients was compromised by 12.5% (p<0.01). Whole body glucose disposal (WGD) was higher at baseline and lower after insulin stimulation. Metabolic flexibility (ΔRER) was lower in the type 2 diabetic patients (0.050±0.033 vs. 0.093±0.050, p<0.01). Mitochondrial function was the sole predictor of basal respiratory exchange ratio (RER) (R(2) = 0.18, p<0.05); whereas WGD predicted both insulin-stimulated RER (R(2) = 0.29, p<0.001) and metabolic flexibility (R(2) = 0.40, p<0.001). CONCLUSIONS: These results indicate that defects in skeletal muscle in vivo mitochondrial function in type 2 diabetic patients are only reflected in basal substrate oxidation and highlight the importance of glucose disposal rate as a determinant of substrate utilization in response to insulin. |
| first_indexed | 2024-12-10T06:16:31Z |
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| id | doaj.art-d2b17bf1b0a94fcea68f7acd9ca0f086 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T06:16:31Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d2b17bf1b0a94fcea68f7acd9ca0f0862022-12-22T01:59:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5164810.1371/journal.pone.0051648Relationships between mitochondrial function and metabolic flexibility in type 2 diabetes mellitus.Tineke van de WeijerLauren Marie SparksEsther PhielixRuth Carla MeexNoud Antonius van HerpenMatthijs Karel C HesselinkPatrick SchrauwenVera Bettina Schrauwen-HinderlingINTRODUCTION: Mitochondrial dysfunction, lipid accumulation, insulin resistance and metabolic inflexibility have been implicated in the etiology of type 2 diabetes (T2D), yet their interrelationship remains speculative. We investigated these interrelationships in a group of T2D and obese normoglycemic control subjects. METHODS: 49 non-insulin dependent male T2D patients and 54 male control subjects were enrolled, and a hyperinsulinemic-euglycemic clamp and indirect calorimetry were performed. A muscle biopsy was taken and intramyocellular lipid (IMCL) was measured. In vivo mitochondrial function was measured by PCr recovery in 30 T2D patients and 31 control subjects. RESULTS: Fasting NEFA levels were significantly elevated in T2D patients compared with controls, but IMCL was not different. Mitochondrial function in T2D patients was compromised by 12.5% (p<0.01). Whole body glucose disposal (WGD) was higher at baseline and lower after insulin stimulation. Metabolic flexibility (ΔRER) was lower in the type 2 diabetic patients (0.050±0.033 vs. 0.093±0.050, p<0.01). Mitochondrial function was the sole predictor of basal respiratory exchange ratio (RER) (R(2) = 0.18, p<0.05); whereas WGD predicted both insulin-stimulated RER (R(2) = 0.29, p<0.001) and metabolic flexibility (R(2) = 0.40, p<0.001). CONCLUSIONS: These results indicate that defects in skeletal muscle in vivo mitochondrial function in type 2 diabetic patients are only reflected in basal substrate oxidation and highlight the importance of glucose disposal rate as a determinant of substrate utilization in response to insulin.http://europepmc.org/articles/PMC3572106?pdf=render |
| spellingShingle | Tineke van de Weijer Lauren Marie Sparks Esther Phielix Ruth Carla Meex Noud Antonius van Herpen Matthijs Karel C Hesselink Patrick Schrauwen Vera Bettina Schrauwen-Hinderling Relationships between mitochondrial function and metabolic flexibility in type 2 diabetes mellitus. PLoS ONE |
| title | Relationships between mitochondrial function and metabolic flexibility in type 2 diabetes mellitus. |
| title_full | Relationships between mitochondrial function and metabolic flexibility in type 2 diabetes mellitus. |
| title_fullStr | Relationships between mitochondrial function and metabolic flexibility in type 2 diabetes mellitus. |
| title_full_unstemmed | Relationships between mitochondrial function and metabolic flexibility in type 2 diabetes mellitus. |
| title_short | Relationships between mitochondrial function and metabolic flexibility in type 2 diabetes mellitus. |
| title_sort | relationships between mitochondrial function and metabolic flexibility in type 2 diabetes mellitus |
| url | http://europepmc.org/articles/PMC3572106?pdf=render |
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