Skeletal muscle dysfunction in the db/db mouse model of type 2 diabetes

Bayley, Jeppe Seamus; Pedersen, Thomas Klit; Nielsen, Ole Bækgaard

doi:10.1002/mus.25064

Cited by 29 publications

(34 citation statements)

References 38 publications

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“…Furthermore, the db/db mouse, a model of obesity associated with type 2 diabetes, demonstrates contractile dysfunction and the reduced expression of SERCA pump levels in skeletal muscle (Bayley et al. ). However, our data showed no differences in the expression of calcium‐associated proteins between the HFD groups and the CONT group (Fig.…”

Section: Discussionmentioning

confidence: 99%

Long-term, but not short-term high-fat diet induces fiber composition changes and impaired contractile force in mouse fast-twitch skeletal muscle

et al. 2017

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In this study, we investigated the effects of a short‐term and long‐term high‐fat diet (HFD) on morphological and functional features of fast‐twitch skeletal muscle. Male C57BL/6J mice were fed a HFD (60% fat) for 4 weeks (4‐week HFD) or 12 weeks (12‐week HFD). Subsequently, the fast‐twitch extensor digitorum longus muscle was isolated, and the composition of muscle fiber type, expression levels of proteins involved in muscle contraction, and force production on electrical stimulation were analyzed. The 12‐week HFD, but not the 4‐week HFD, resulted in a decreased muscle tetanic force on 100 Hz stimulation compared with control (5.1 ± 1.4 N/g in the 12‐week HFD vs. 7.5 ± 1.7 N/g in the control group; P < 0.05), whereas muscle weight and cross‐sectional area were not altered after both HFD protocols. Morphological analysis indicated that the percentage of type IIx myosin heavy chain fibers, mitochondrial oxidative enzyme activity, and intramyocellular lipid levels increased in the 12‐week HFD group, but not in the 4‐week HFD group, compared with controls (P < 0.05). No changes in the expression levels of calcium handling‐related proteins and myofibrillar proteins (myosin heavy chain and actin) were detected in the HFD models, whereas fast‐troponin T‐protein expression was decreased in the 12‐week HFD group, but not in the 4‐week HFD group (P < 0.05). These findings indicate that a long‐term HFD, but not a short‐term HFD, impairs contractile force in fast‐twitch muscle fibers. Given that skeletal muscle strength largely depends on muscle fiber type, the impaired muscle contractile force by a HFD might result from morphological changes of fiber type composition.

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Section: Discussionmentioning

confidence: 99%

Long-term, but not short-term high-fat diet induces fiber composition changes and impaired contractile force in mouse fast-twitch skeletal muscle

et al. 2017

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“…44 It has been known for 50 years that DM is associated with slower nerve conduction velocity. 45 Slower conduction velocities have been reported in the tibial nerve, 40,46,47 peroneal nerve 46–48 and median nerve.…”

Section: The Effects Of Dpn On Skeletal Muscle Functionmentioning

confidence: 99%

“…Muscle atrophy directly contributes to the declines in muscle force. 32,38,39,60 Muscle relaxation rates are prolonged, 44 partially attributed to decreased calcium handling as the smooth endoplasmic reticulum ATPase (SERCA) protein content is reduced with DPN. 44 The rate of force development is also reduced with DPN, as indicated by a longer time to reach peak force.…”

Section: The Effects Of Dpn On Skeletal Muscle Functionmentioning

confidence: 99%

“…32,38,39,60 Muscle relaxation rates are prolonged, 44 partially attributed to decreased calcium handling as the smooth endoplasmic reticulum ATPase (SERCA) protein content is reduced with DPN. 44 The rate of force development is also reduced with DPN, as indicated by a longer time to reach peak force. 38,44 Specific force relative to muscle area in the dorsiflexors has also been reported in DPN, 39,59 suggesting declines in muscle quality.…”

Section: The Effects Of Dpn On Skeletal Muscle Functionmentioning

confidence: 99%

“…44 The rate of force development is also reduced with DPN, as indicated by a longer time to reach peak force. 38,44 Specific force relative to muscle area in the dorsiflexors has also been reported in DPN, 39,59 suggesting declines in muscle quality. However, the voluntary activation of skeletal muscle or ability to fully recruit the muscle appears to be preserved in DPN.…”

Section: The Effects Of Dpn On Skeletal Muscle Functionmentioning

confidence: 99%

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Declining Skeletal Muscle Function in Diabetic Peripheral Neuropathy

Parasoglou

Rao

Slade

2017

Clinical Therapeutics

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Purpose In this review, we highlight the current concepts in the effects of diabetic peripheral neuropathy (DPN) in skeletal muscle. We discuss the lack of effective pharmacological treatments and the role of physical exercise intervention in limb protection and symptom reversal. We also highlight the importance of Magnetic Resonance Imaging (MRI) techniques in providing a mechanistic understanding of the disease and helping develop targeted treatments. Methods This review provides a comprehensive reporting on the effects of DPN in the skeletal muscle of diabetic patients. It also provides an update on the most recent trials of exercise intervention targeting DPN pathology. Lastly, we report on emerging MRI techniques that have shown promise in providing a mechanistic understanding of DPN and can help improve the design and implementation of clinical trials in the future. Findings Impairments in lower limb muscles reduce functional capacity and contribute to altered gait, increased fall risk, and impaired balance in patients with DPN. This is an important concern for DPN patients as their falls are very likely to be injurious, and lead to bone fractures, poorly healing wounds, and chronic infections that may require amputation. Preliminary studies have shown that moderate intensity exercise programs are well tolerated by patients with DPN. They can improve their cardiorespiratory function and can partially reverse some of the DPN symptoms. MRI has the potential to bring new mechanistic insights into the effects of DPN as well as to objectively measure small changes in DPN pathology as a result of intervention. Implications Non-invasive exercise intervention is particularly valuable in DPN due to its safety, low cost, and potential to augment pharmacological interventions. As we gain a better mechanistic understanding of the disease, more targeted and effective interventions can be designed.

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Diabetes induces differences in the F‐actin spatial organization of striated muscles

2020

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Studies have shown the cytoskeleton disorganization produced by diabetes and quantified F‐actin fluorescence in the striated muscles of diabetic animals. However, at present, there are no studies that have quantified F‐actin spatial organization (F‐actin‐SO). Through our research, we analyzed the effect of diabetes on F‐actin‐SO in the cardiac and skeletal muscles of a mouse model. The muscle samples were labeled with phalloidin–rhodamine and analyzed with confocal microscopy. The analysis was done in two dimensions using four approaches: quantitation of (a) phalloidin‐occupied areas; (b) number of F‐actin‐unoccupied areas per muscular fiber; (c) F‐actin filament discontinuity; and (d) costamere periodicity. Our results showed that both the cardiac and skeletal muscles of the control mice had more phalloidin‐occupied areas than the diabetic mice. The skeletal muscles had a significantly higher number of F‐actin‐unoccupied areas per muscular fiber and more F‐actin discontinuities. Additionally, using western blot analyses, we showed that those differences were not due to α‐actin protein expression. Finally, we considered the importance of these findings in dysfunctional contraction, disassembly in cell–cell communication, conduction of muscle impulse, and changes in cell nanomechanics. Our results quantitatively demonstrated that diabetes severely affects F‐actin‐SO in striated muscles.

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Skeletal muscle dysfunction in the db/db mouse model of type 2 diabetes

Cited by 29 publications

References 38 publications

Long-term, but not short-term high-fat diet induces fiber composition changes and impaired contractile force in mouse fast-twitch skeletal muscle

Long-term, but not short-term high-fat diet induces fiber composition changes and impaired contractile force in mouse fast-twitch skeletal muscle

Declining Skeletal Muscle Function in Diabetic Peripheral Neuropathy

Diabetes induces differences in the F‐actin spatial organization of striated muscles

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