Dataset Information

Effect of insulin insufficiency on ultrastructure and function in skeletal muscle.

ABSTRACT:

Background

Decreased insulin availability and high blood glucose levels, the hallmark features of poorly controlled diabetes, drive disease progression and are associated with decreased skeletal muscle mass. We have shown that mice with β-cell dysfunction and normal insulin sensitivity have decreased skeletal muscle mass. This project asks how insulin deficiency impacts on the structure and function of the remaining skeletal muscle in these animals.

Methods

Skeletal muscle function was determined by measuring exercise capacity and specific muscle strength prior to and after insulin supplementation for 28 days in 12-week-old mice with conditional β-cell deletion of the ATP binding cassette transporters ABCA1 and ABCG1 (β-DKO mice). Abca1 and Abcg1 floxed (fl/fl) mice were used as controls. RNAseq was used to quantify changes in transcripts in soleus and extensor digitorum longus muscles. Skeletal muscle and mitochondrial morphology were assessed by transmission electron microscopy. Myofibrillar Ca²⁺ sensitivity and maximum isometric single muscle fibre force were assessed using MyoRobot biomechatronics technology.

Results

RNA transcripts were significantly altered in β-DKO mice compared with fl/fl controls (32 in extensor digitorum longus and 412 in soleus). Exercise capacity and muscle strength were significantly decreased in β-DKO mice compared with fl/fl controls (P = 0.012), and a loss of structural integrity was also observed in skeletal muscle from the β-DKO mice. Supplementation of β-DKO mice with insulin restored muscle integrity, strength and expression of 13 and 16 of the dysregulated transcripts in and extensor digitorum longus and soleus muscles, respectively.

Conclusions

Insulin insufficiency due to β-cell dysfunction perturbs the structure and function of skeletal muscle. These adverse effects are rectified by insulin supplementation.

SUBMITTER: Kopecky C

PROVIDER: S-EPMC10834341 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Effect of insulin insufficiency on ultrastructure and function in skeletal muscle.

Kopecky Chantal C Haug Michael M Reischl Barbara B Deshpande Nandan N Manandhar Bikash B King Thomas W TW Lee Victoria V Wilkins Marc R MR Morris Margaret M Polly Patsie P Friedrich Oliver O Rye Kerry-Anne KA Cochran Blake J BJ

Journal of cachexia, sarcopenia and muscle 20231220 1

<h4>Background</h4>Decreased insulin availability and high blood glucose levels, the hallmark features of poorly controlled diabetes, drive disease progression and are associated with decreased skeletal muscle mass. We have shown that mice with β-cell dysfunction and normal insulin sensitivity have decreased skeletal muscle mass. This project asks how insulin deficiency impacts on the structure and function of the remaining skeletal muscle in these animals.<h4>Methods</h4>Skeletal muscle functio ...[more]

PMID: 38124345

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Project description:AimsWeight excess and insulin resistance predispose to heart failure. High sodium consumption may contribute to the development of cardiac impairment in insulin-resistant individuals by promoting inadequate skeletal muscle microvascular perfusion response to insulin. We sought to investigate the association of dietary sodium reduction with muscle perfusion, insulin sensitivity, and cardiac function in overweight/obese insulin-resistant (O-IR) normotensive subjects.Methods and resultsFifty O-IR individuals with higher than recommended sodium intake were randomized to usual or reduced sodium diet for 8 weeks; 25 lean, healthy subjects served as controls for pre-intervention measurements. Echocardiography and muscle perfusion were performed during fasting and under stable euglycaemic-hyperinsulinaemic clamp conditions. O-IR patients demonstrated subclinical cardiac dysfunction as evidenced by lower left ventricular global longitudinal strain (GLS), e' tissue velocity, and left atrial strain and reduced muscle perfusion. The intervention arm showed improvements in insulin resistance [glucose infusion rate (GIR)], GLS, e', atrial strain, and muscle perfusion in fasting conditions, as well as improved responses of GLS and muscle perfusion to insulin during clamp. Significant interactions were found between the allocation to low-salt diet and improvement in muscle perfusion on change in GIR at follow-up (P = 0.030), and between improvement in muscle perfusion and change in GIR on change in GLS response to insulin at follow-up (P = 0.026). Mediation analysis revealed that the relationship between the reduction of sodium intake and improvement in GLS was mediated by improvements in muscle perfusion and GIR (decrease in beta coefficient from -0.29 to -0.16 after the inclusion of mediator variables to the model).ConclusionsThe reduction of dietary sodium in the normotensive O-IR population improves cardiac function, and this effect may be associated with the concomitant improvements in skeletal muscle perfusion and insulin resistance. These findings might contribute to refining heart failure preventive strategies.

Dataset Information

Effect of insulin insufficiency on ultrastructure and function in skeletal muscle.

Background

Methods

Results

Conclusions

Publications

Effect of insulin insufficiency on ultrastructure and function in skeletal muscle.

Similar Datasets

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