Gymnastik- och idrottshögskolan, GIH

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Edman, S., Flockhart, M., Larsen, F. J. & Apro, W. (2024). Need for Speed: Human fast-twitch mitochondria favor power over efficiency.. Molecular Metabolism, 79, Article ID 101854.
Åpne denne publikasjonen i ny fane eller vindu >>Need for Speed: Human fast-twitch mitochondria favor power over efficiency.
2024 (engelsk)Inngår i: Molecular Metabolism, ISSN 2212-8778, Vol. 79, artikkel-id 101854Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

OBJECTIVE: Human skeletal muscle consists of a mixture of slow- and fast-twitch fibers with distinct capacities for contraction mechanics, fermentation, and oxidative phosphorylation (OXPHOS). While the divergence in mitochondrial volume favoring slow-twitch fibers is well established, data on the fiber type-specific intrinsic mitochondrial function and morphology are highly limited with existing data mainly being generated in animal models. This highlights the need for more human data on the topic.

METHODS: Here, we utilized THRIFTY, a rapid fiber type identification protocol to detect, sort, and pool fast- and slow-twitch fibers within six hours of muscle biopsy sampling. Respiration of permeabilized fast- and slow-twitch fiber pools was then analyzed with high-resolution respirometry. Using standardized western blot procedures, muscle fiber pools were subsequently analyzed for control proteins and key proteins related to respiratory capacity.

RESULTS: Maximal complex I CI+II respiration was 25% higher in human slow-twitch fibers compared to fast-twitch fibers. However, per volume, the respiratory rate of mitochondria in fast-twitch fibers was approximately 50% higher for CI+II, which was primarily mediated through elevated CII respiration, but not CI or. Furthermore, the abundance of CII protein and proteins regulating cristae structure were disproportionally elevated in mitochondria of the fast-twitch fibers. The difference in intrinsic respiratory rate was not reflected in fatty acid- or complex I respiration.

CONCLUSION: Mitochondria of human fast-twitch muscle fibers compensate for their lack of volume by substantially elevating intrinsic respiratory rate through increased reliance on complex II.

sted, utgiver, år, opplag, sider
Elsevier, 2024
HSV kategori
Forskningsprogram
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-8000 (URN)10.1016/j.molmet.2023.101854 (DOI)001147759100001 ()38104652 (PubMedID)
Tilgjengelig fra: 2023-12-20 Laget: 2023-12-20 Sist oppdatert: 2024-02-22
Horwath, O., Nordström, F., von Walden, F., Apro, W. & Moberg, M. (2023). Acute hypoxia attenuates resistance exercise-induced ribosome signaling but does not impact satellite cell pool expansion in human skeletal muscle.. The FASEB Journal, 37(3), Article ID e22811.
Åpne denne publikasjonen i ny fane eller vindu >>Acute hypoxia attenuates resistance exercise-induced ribosome signaling but does not impact satellite cell pool expansion in human skeletal muscle.
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2023 (engelsk)Inngår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 37, nr 3, artikkel-id e22811Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Cumulative evidence supports the hypothesis that hypoxia acts as a regulator of muscle mass. However, the underlying molecular mechanisms remain incompletely understood, particularly in human muscle. Here we examined the effect of hypoxia on signaling pathways related to ribosome biogenesis and myogenic activity following an acute bout of resistance exercise. We also investigated whether hypoxia influenced the satellite cell response to resistance exercise. Employing a randomized, crossover design, eight men performed resistance exercise in normoxia (FiO2 21%) or normobaric hypoxia (FiO2 12%). Muscle biopsies were collected in a time-course manner (before, 0, 90, 180 min and 24 h after exercise) and were analyzed with respect to cell signaling, gene expression and satellite cell content using immunoblotting, RT-qPCR and immunofluorescence, respectively. In normoxia, resistance exercise increased the phosphorylation of RPS6, TIF-1A and UBF above resting levels. Hypoxia reduced the phosphorylation of these targets by ~37%, ~43% and ~ 67% throughout the recovery period, respectively (p < .05 vs. normoxia). Resistance exercise also increased 45 S pre-rRNA expression and mRNA expression of c-Myc, Pol I and TAF-1A above resting levels, but no differences were observed between conditions. Similarly, resistance exercise increased mRNA expression of myogenic regulatory factors throughout the recovery period and Pax7+ cells were elevated 24 h following exercise in mixed and type II muscle fibers, with no differences observed between normoxia and hypoxia. In conclusion, acute hypoxia attenuates ribosome signaling, but does not impact satellite cell pool expansion and myogenic gene expression following a bout of resistance exercise in human skeletal muscle.

sted, utgiver, år, opplag, sider
John Wiley & Sons, 2023
Emneord
Pax7, muscle fiber, myogenesis, resistance exercise, ribosome biogenesis
HSV kategori
Forskningsprogram
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-7523 (URN)10.1096/fj.202202065RR (DOI)000936598200001 ()36786723 (PubMedID)
Forskningsfinansiär
Swedish National Centre for Research in Sports, D2017- 0012, D2019- 0050, D2019- 0035
Tilgjengelig fra: 2023-03-06 Laget: 2023-03-06 Sist oppdatert: 2023-03-23
Flockhart, M., Nilsson, L., Tillqvist, E. N., Vinge, F., Millbert, F., Lännerström, J., . . . Larsen, F. J. (2023). Glucosinolate-rich broccoli sprouts protect against oxidative stress and improve adaptations to intense exercise training.. Redox Biology, 67, Article ID 102873.
Åpne denne publikasjonen i ny fane eller vindu >>Glucosinolate-rich broccoli sprouts protect against oxidative stress and improve adaptations to intense exercise training.
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2023 (engelsk)Inngår i: Redox Biology, E-ISSN 2213-2317, Vol. 67, artikkel-id 102873Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Oxidative stress plays a vital role for the adaptive responses to physical training. However, excessive oxidative stress can precipitate cellular damage, necessitating protective mechanisms to mitigate this effect. Glucosinolates, found predominantly in cruciferous vegetables, can be converted into isothiocyanates, known for their antioxidative properties. These compounds activate crucial antioxidant defence pathways and support mitochondrial function and protein integrity under oxidative stress, in both Nrf2-dependent and independent manners. We here administered glucosinolate-rich broccoli sprouts (GRS), in a randomized double-blinded cross-over fashion to 9 healthy subjects in combination with daily intense exercise training for 7 days. We found that exercise in combination with GRS significantly decreased the levels of carbonylated proteins in skeletal muscle and the release of myeloperoxidase into blood. Moreover, it lowered lactate accumulation during submaximal exercise, and attenuated the severe nocturnal hypoglycaemic episodes seen during the placebo condition. Furthermore, GRS in combination with exercise improved physical performance, which was unchanged in the placebo condition.

sted, utgiver, år, opplag, sider
Elsevier, 2023
HSV kategori
Forskningsprogram
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-7791 (URN)10.1016/j.redox.2023.102873 (DOI)001074895800001 ()37688976 (PubMedID)
Forskningsfinansiär
Ekhaga FoundationSwedish National Centre for Research in Sports
Merknad

This study was funded by grants from Ekhagastiftelsen, Swedish Research Council for Sport Science and Sydgrönt Ekonomisk Förening.

Tilgjengelig fra: 2023-09-14 Laget: 2023-09-14 Sist oppdatert: 2024-01-04
Blackwood, S. J., Horwath, O., Moberg, M., Pontén, M., Apro, W., Ekblom, M., . . . Katz, A. (2023). Insulin resistance after a 3-day fast is associated with an increased capacity of skeletal muscle to oxidize lipids.. American Journal of Physiology. Endocrinology and Metabolism, 324(5), E390-E401
Åpne denne publikasjonen i ny fane eller vindu >>Insulin resistance after a 3-day fast is associated with an increased capacity of skeletal muscle to oxidize lipids.
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2023 (engelsk)Inngår i: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 324, nr 5, s. E390-E401Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

There is a debate on whether lipid-mediated insulin resistance derives from an increased or decreased capacity of muscle to oxidize fats. Here we examine the involvement of muscle fiber composition in the metabolic responses to a 3-day fast (starvation, which results in increases in plasma lipids and insulin resistance) in two groups of healthy young subjects: 1, area occupied by type I fibers = 61.0 ± 11.8%; 2, type I area = 36.0 ± 4.9% (P<0.001). Muscle biopsies and intravenous glucose tolerance tests were performed after an overnight fast and after starvation. Biopsies were analyzed for muscle fiber composition and mitochondrial respiration. Indices of glucose tolerance and insulin sensitivity were determined. Glucose tolerance was similar in both groups after an overnight fast and deteriorated to a similar degree in both groups after starvation. In contrast, whole-body insulin sensitivity decreased markedly after starvation in group 1 (P<0.01), whereas the decrease in group 2 was substantially smaller (P=0.06). Non-esterified fatty acids and β-hydroxybutyrate levels in plasma after an overnight fast were similar between groups and increased markedly and comparably in both groups after starvation, demonstrating similar degrees of lipid load. The capacity of permeabilized muscle fibers to oxidize lipids was significantly higher in group 1 vs. 2, whereas there was no significant difference in pyruvate oxidation between groups. The data demonstrate that loss of whole-body insulin sensitivity after short-term starvation is a function of muscle fiber composition and is associated with an elevated rather than a diminished capacity of muscle to oxidize lipids.

sted, utgiver, år, opplag, sider
American Physiological Society, 2023
Emneord
glucose tolerance, insulin resistance, mitochondrial respiration, muscle fiber composition, starvation
HSV kategori
Forskningsprogram
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-7521 (URN)10.1152/ajpendo.00317.2022 (DOI)000974241700002 ()36791323 (PubMedID)
Tilgjengelig fra: 2023-03-03 Laget: 2023-03-03 Sist oppdatert: 2024-01-11
Lilja, M., Moberg, M., Apro, W., Martínez-Aranda, L. M., Rundqvist, H., Langlet, B., . . . Lundberg, T. R. (2023). Limited effect of over-the-counter doses of ibuprofen on mechanisms regulating muscle hypertrophy during resistance training in young adults.. Journal of applied physiology, 134(3), 753-765
Åpne denne publikasjonen i ny fane eller vindu >>Limited effect of over-the-counter doses of ibuprofen on mechanisms regulating muscle hypertrophy during resistance training in young adults.
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2023 (engelsk)Inngår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 134, nr 3, s. 753-765Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

We have previously shown that maximal over-the-counter doses of ibuprofen, compared with low doses of acetylsalicylic acid, reduce muscle hypertrophy in young individuals after 8 weeks of resistance training. Because the mechanism behind this effect has not been fully elucidated, we here investigated skeletal muscle molecular responses and myofiber adaptations in response to acute and chronic resistance training with concomitant drug intake. Thirty-one young (aged 18-35 years) healthy men (n=17) and women (n=14) were randomized to receive either ibuprofen (IBU;1200mg daily; n=15) or acetylsalicylic acid (ASA; 75mg daily; n=16) while undergoing 8 weeks of knee extension training. Muscle biopsies from the vastus lateralis were obtained before, at week 4 after an acute exercise session, and after 8 weeks of resistance training and analyzed for mRNA markers and mTOR signaling, as well as quantification of total RNA content (marker of ribosome biogenesis) and immunohistochemical analyzes of muscle fiber size, satellite cell content, myonuclear accretion, and capillarization. There were only two treatment ´ time interaction in selected molecular markers after acute exercise (atrogin-1 and MuRF1 mRNA), but several exercise effects. Muscle fiber size, satellite cell and myonuclear accretion, and capillarization were not affected by chronic training or drug intake. RNA content increased comparably (~14%) in both groups. Collectively, these data suggest that established acute and chronic hypertrophy regulators (including mTOR signaling, ribosome biogenesis, satellite cell content, myonuclear accretion, and angiogenesis) were not differentially affected between groups and therefore do not explain the deleterious effects of ibuprofen on muscle hypertrophy in young adults.

sted, utgiver, år, opplag, sider
American Physiological Society, 2023
Emneord
Non-steroidal anti-inflammatory drugs, Resistance exercise, Ribosome biogenesis, Satellite cells, Skeletal muscle
HSV kategori
Forskningsprogram
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-7522 (URN)10.1152/japplphysiol.00698.2022 (DOI)000972694300002 ()36794689 (PubMedID)
Tilgjengelig fra: 2023-03-03 Laget: 2023-03-03 Sist oppdatert: 2023-06-12
Flockhart, M., Tischer, D., Nilsson, L. C., Blackwood, S. J., Ekblom, B., Katz, A., . . . Larsen, F. J. (2023). Reduced glucose tolerance and insulin sensitivity after prolonged exercise in endurance athletes.. Acta Physiologica, 238(4), Article ID e13972.
Åpne denne publikasjonen i ny fane eller vindu >>Reduced glucose tolerance and insulin sensitivity after prolonged exercise in endurance athletes.
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2023 (engelsk)Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 238, nr 4, artikkel-id e13972Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

AIM: The purpose of this study was to 1. investigate if glucose tolerance is affected after one acute bout of different types of exercise; 2. assess if potential differences between two exercise paradigms are related to changes in mitochondrial function; and 3. determine if endurance athletes differ from nonendurance-trained controls in their metabolic responses to the exercise paradigms.

METHODS: Nine endurance athletes (END) and eight healthy nonendurance-trained controls (CON) were studied. Oral glucose tolerance tests (OGTT) and mitochondrial function were assessed on three occasions: in the morning, 14 h after an overnight fast without prior exercise (RE), as well as after 3 h of prolonged continuous exercise at 65% of VO2 max (PE) or 5 × 4 min at ~95% of VO2 max (HIIT) on a cycle ergometer.

RESULTS: Glucose tolerance was markedly reduced in END after PE compared with RE. END also exhibited elevated fasting serum FFA and ketones levels, reduced insulin sensitivity and glucose oxidation, and increased fat oxidation during the OGTT. CON showed insignificant changes in glucose tolerance and the aforementioned measurements compared with RE. HIIT did not alter glucose tolerance in either group. Neither PE nor HIIT affected mitochondrial function in either group. END also exhibited increased activity of 3-hydroxyacyl-CoA dehydrogenase activity in muscle extracts vs. CON.

CONCLUSION: Prolonged exercise reduces glucose tolerance and increases insulin resistance in endurance athletes the following day. These findings are associated with an increased lipid load, a high capacity to oxidize lipids, and increased fat oxidation.

sted, utgiver, år, opplag, sider
John Wiley & Sons, 2023
Emneord
endurance athletes, endurance exercise, glucose tolerance, insulin sensitivity, mitochondria, reactive oxygen species
HSV kategori
Forskningsprogram
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-7627 (URN)10.1111/apha.13972 (DOI)000972308100001 ()37017615 (PubMedID)
Forskningsfinansiär
Swedish National Centre for Research in Sports, P2017-0067, P2018-0083, P2019-0062, P2020-0061
Merknad

At the time of Mikael Flockhart's dissertation, this article was a submitted manuscript.

Tilgjengelig fra: 2023-05-08 Laget: 2023-05-08 Sist oppdatert: 2023-08-29
Nordström, F., Liegnell, R., Apro, W., Blackwood, S. J., Katz, A. & Moberg, M. (2023). The lactate receptor GPR81 is predominantly expressed in type II human skeletal muscle fibers: potential for lactate autocrine signaling.. Paper presented at 324(2):C477-C487. American Journal of Physiology - Cell Physiology, 324(2), C477-C487
Åpne denne publikasjonen i ny fane eller vindu >>The lactate receptor GPR81 is predominantly expressed in type II human skeletal muscle fibers: potential for lactate autocrine signaling.
Vise andre…
2023 (engelsk)Inngår i: American Journal of Physiology - Cell Physiology, ISSN 0363-6143, E-ISSN 1522-1563, Vol. 324, nr 2, s. C477-C487Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

GPR81 was first identified in adipocytes as a receptor for L-lactate, which upon binding inhibits cAMP-PKA-CREB signaling. Moreover, incubation of myotubes with lactate augments expression of GPR81 and genes and proteins involved in lactate- and energy metabolism. However, characterization of GPR81 expression and investigation of related signaling in human skeletal muscle under conditions of elevated circulating lactate levels are lacking. Muscle biopsies were obtained from healthy men and women at rest, after leg extension exercise, with or without venous infusion of sodium lactate, and 90 and 180 min after exercise (8 men and 8 women). Analyses included protein and mRNA levels of GPR81, as well as GPR81-dependent signaling molecules. GPR81 expression was 2.5-fold higher in type II glycolytic compared with type I oxidative muscle fibers, and the expression was inversely related to the percentage of type I muscle fibers. Muscle from women expressed about 25% more GPR81 protein than from men. Global PKA-activity increased by 5-8% after exercise, with no differences between trials. CREBS133 phosphorylation was reduced by 30% after exercise and remained repressed during the entire trials, with no influence of the lactate infusion. The mRNA expression of VEGF and PGC-1α were increased by 2.5 - 6-fold during recovery, and that of LDH reduced by 15% with no differences between trials for any gene at any time point. The high expression of GPR81-protein in type II fibers suggests that lactate functions as an autocrine signaling molecule in muscle; however, lactate does not appear to regulate CREB signaling during exercise.

sted, utgiver, år, opplag, sider
American Physiological Society, 2023
Emneord
CREB, HCAR1, PGC-1alpha, PKA, Resistance exercise
HSV kategori
Forskningsprogram
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-7464 (URN)10.1152/ajpcell.00443.2022 (DOI)000959663400012 ()36622074 (PubMedID)
Konferanse
324(2):C477-C487
Tilgjengelig fra: 2023-01-11 Laget: 2023-01-11 Sist oppdatert: 2023-05-18
Edman, S., Horwath, O. & Apro, W. (2023). THRIFTY - A High-throughput Single Muscle Fiber Typing Method Based on Immunofluorescence Detection. Bio-protocol, 13(10), Article ID e4678.
Åpne denne publikasjonen i ny fane eller vindu >>THRIFTY - A High-throughput Single Muscle Fiber Typing Method Based on Immunofluorescence Detection
2023 (engelsk)Inngår i: Bio-protocol, E-ISSN 2331-8325, Vol. 13, nr 10, artikkel-id e4678Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Skeletal muscle consists of a mixture of fiber types with different functional and metabolic characteristics. The relative composition of these muscle fiber types has implications for muscle performance, whole-body metabolism, and health. However, analyses of muscle samples in a fiber type-dependent manner are very time consuming. Therefore, these are often neglected in favor of more time-efficient analyses on mixed muscle samples. Methods such as western blot and myosin heavy chain separation by SDS-PAGE have previously been utilized to fiber type-isolated muscle fibers. More recently, the introduction of the dot blot method significantly increased the speed of fiber typing. However, despite recent advancements, none of the current methodologies are feasible for large-scale investigations because of their time requirements. Here, we present the protocol for a new method, which we have named THRIFTY (high-THRoughput Immunofluorescence Fiber TYping), that enables rapid fiber type identification using antibodies towards the different myosin heavy chain (MyHC) isoforms of fast and slow twitch muscle fibers. First, a short segment (<1 mm) is cut off from isolated muscle fibers and mounted on a customized gridded microscope slide holding up to 200 fiber segments. Second, the fiber segments attached to the microscope slide are stained with MyHC-specific antibodies and then visualized using a fluorescence microscope. Lastly, the remaining pieces of the fibers can either be collected individually or pooled together with fibers of the same type for subsequent analyses. The THRIFTY protocol is approximately three times as fast as the dot blot method, which enables not only time-sensitive assays to be performed but also increases the feasibility to conduct large-scale investigations into fiber type specific physiology.

sted, utgiver, år, opplag, sider
Bio-protocol, 2023
Emneord
Muscle fiber type, Myosin heavy chain, Fiber type identification, Muscle
HSV kategori
Forskningsprogram
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-7950 (URN)10.21769/BioProtoc.4678 (DOI)001089324100006 ()37251094 (PubMedID)
Tilgjengelig fra: 2023-11-20 Laget: 2023-11-20 Sist oppdatert: 2023-11-20
Moberg, M., Apro, W., Horwath, O., van Hall, G., Blackwood, S. J. & Katz, A. (2022). Acute normobaric hypoxia blunts contraction-mediated mTORC1- and JNK-signaling in human skeletal muscle.. Acta Physiologica, 234(2), Article ID e13771.
Åpne denne publikasjonen i ny fane eller vindu >>Acute normobaric hypoxia blunts contraction-mediated mTORC1- and JNK-signaling in human skeletal muscle.
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2022 (engelsk)Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 234, nr 2, artikkel-id e13771Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

AIM: Hypoxia has been shown to reduce resistance exercise-induced stimulation of protein synthesis and long-term gains in muscle mass. However, the mechanism whereby hypoxia exerts its effect is not clear. Here we examine the effect of acute hypoxia on the activity of several signaling pathways involved in regulation of muscle growth following a bout of resistance exercise.

METHODS: Eight men performed two sessions of leg resistance exercise in Normoxia or Hypoxia (12% O2 ) in a randomized crossover fashion. Muscle biopsies were obtained at rest and at 0, 90,180 min after exercise. Muscle analyses included levels of signaling proteins and metabolites associated with energy turnover.

RESULTS: Exercise during Normoxia induced a 5-10-fold increase of S6K1Thr389 phosphorylation throughout the recovery period, but Hypoxia blunted the increases by ~50%. Phosphorylation of JNKThr183/Tyr185 and the JNK target SMAD2Ser245/250/255 was increased by 30-40-fold immediately after exercise in Normoxia, but Hypoxia blocked almost 70% of the activation. Throughout recovery, phosphorylation of JNK and SMAD2 remained elevated following exercise in Normoxia, but the effect of Hypoxia was lost at 90-180 min post-exercise. Hypoxia had no effect on exercise induced Hippo- or autophagy-signaling and ubiquitin-proteasome related protein levels. Nor did Hypoxia alter the changes induced by exercise in high energy phosphates, glucose 6-P, lactate, or phosphorylation of AMPK or ACC.

CONCLUSION: We conclude that acute severe hypoxia inhibits resistance exercise induced mTORC1- and JNK signaling in human skeletal muscle, effects that do not appear to be mediated by changes in the degree of metabolic stress in the muscle.

sted, utgiver, år, opplag, sider
John Wiley & Sons, 2022
Emneord
FSR, Hippo-pathway, Muscle metabolites, deuterium oxide, oxygen
HSV kategori
Forskningsprogram
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-6900 (URN)10.1111/apha.13771 (DOI)000744361300001 ()34984845 (PubMedID)
Forskningsfinansiär
Swedish National Centre for Research in Sports, D2017--0012
Tilgjengelig fra: 2022-01-10 Laget: 2022-01-10 Sist oppdatert: 2022-02-08
Blackwood, S. J., Horwath, O., Moberg, M., Pontén, M., Apro, W., Ekblom, M., . . . Katz, A. (2022). Extreme Variations in Muscle Fiber Composition Enable Detection of Insulin Resistance and Excessive Insulin Secretion.. Journal of Clinical Endocrinology and Metabolism, 107(7), e2729-e2737, Article ID dgac221.
Åpne denne publikasjonen i ny fane eller vindu >>Extreme Variations in Muscle Fiber Composition Enable Detection of Insulin Resistance and Excessive Insulin Secretion.
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2022 (engelsk)Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 107, nr 7, s. e2729-e2737, artikkel-id dgac221Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

CONTEXT: Muscle fiber composition is associated with peripheral insulin action.

OBJECTIVE: We investigated whether extreme differences in muscle fiber composition are associated with alterations in peripheral insulin action and secretion in young, healthy subjects who exhibit normal fasting glycemia and insulinemia.

METHODS: Relaxation time following a tetanic contraction was used to identify subjects with a high or low expression of type I muscle fibers: group I (n=11), area occupied by type I muscle fibers = 61.0 ± 11.8%; group II (n=8), type I area = 36.0 ± 4.9% (P<0.001). Biopsies were obtained from the vastus lateralis muscle and analyzed for mitochondrial respiration on permeabilized fibers, muscle fiber composition and capillary density. An intravenous glucose tolerance test was performed and indices of glucose tolerance, insulin sensitivity and secretion were determined.

RESULTS: Glucose tolerance was similar between groups, whereas whole-body insulin sensitivity was decreased by ~50% in group II vs group I (P=0.019). First phase insulin release (area under the insulin curve during 10 min after glucose infusion) was increased by almost 4-fold in group II vs I (P=0.01). Whole-body insulin sensitivity was correlated with % area occupied by type I fibers (r=0.54; P=0.018) and capillary density in muscle (r=0.61; P=0.005), but not with mitochondrial respiration. Insulin release was strongly related to % area occupied by type II fibers (r=0.93; P<0.001).

CONCLUSIONS: Assessment of muscle contractile function in young healthy subjects may prove useful in identifying individuals with insulin resistance and enhanced glucose stimulated insulin secretion prior to onset of clinical manifestations.

sted, utgiver, år, opplag, sider
Oxford University Press, 2022
Emneord
insulin, insulin resistance, insulin secretion, intravenous glucose tolerance test, mitochondrial respiration, muscle fiber type
HSV kategori
Forskningsprogram
Medicin/Teknik; Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-7053 (URN)10.1210/clinem/dgac221 (DOI)000789019300001 ()35405014 (PubMedID)
Tilgjengelig fra: 2022-05-18 Laget: 2022-05-18 Sist oppdatert: 2022-12-06
Prosjekter
From single fiber to whole muscle - glycogen availability and exercise-induced autophagy [D2019-0050]; Gymnastik- och idrottshögskolan, GIHLow glycogen availability induces superior autophagy activation in type II fibers after exercise [CIF P2021-0173]; Gymnastik- och idrottshögskolan, GIHAminosyror och låga glykogennivåer förstärker anabol signalering i typ I fibrer efter träning [CIF P2022-0022]; Gymnastik- och idrottshögskolan, GIHEffekt av glykogentillgänglighet på muskelnedbrytning med fokus på ubiquitin proteasome systemet [CIF P2023-0116]; Gymnastik- och idrottshögskolan, GIHLåg glykogentillgänglighet och proteasome-medierad muskelnedbrytning i typ I och typ II muskelfibrer [P2024-0096]; Gymnastik- och idrottshögskolan, GIH
Organisasjoner
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0003-1942-2919