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Preventing muscle w...
Preventing muscle wasting: pro-insulin C-peptide prevents loss in muscle mass in streptozotocin-diabetic rats
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Maurotti, S. (author)
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Pujia, R. (author)
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Galluccio, A. (author)
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Nucera, S. (author)
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Musolino, V. (author)
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Mare, R. (author)
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Frosina, M. (author)
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Noto, F. R. (author)
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Mollace, V. (author)
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- Romeo, Stefano, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Pujia, A. (author)
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Montalcini, T. (author)
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(creator_code:org_t)
- 2023-03-06
- 2023
- English.
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In: Journal of Cachexia Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 14:2, s. 1117-1129
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- BackgroundC-peptide therapy exerts several positive actions on nerves, vasculature, smooth muscle relaxation, kidney function and bone. To date, the role of C-peptide in preventing type 1 diabetes-related muscle atrophy has not been investigated. Our aim was to evaluate if C-peptide infusion prevents muscle wasting in diabetic rats. MethodsTwenty-three male Wistar rats were randomly divided into three groups: normal control group, diabetic group and diabetic group plus C-peptide. Diabetes was induced by streptozotocin injection, and C-peptide was administered subcutaneously for 6 weeks. The blood samples were obtained at baseline, before streptozotocin injection and at the end of the study to assess C-peptide, ubiquitin and other laboratory parameters. We also tested the ability of C-peptide to regulate the skeletal muscle mass, the ubiquitin-proteasome system, the autophagy pathway as well as to improve muscle quality. ResultsC-peptide administration reversed hyperglycaemia (P = 0.02) and hypertriglyceridaemia (P = 0.01) in diabetic plus C-peptide rats compared with diabetic control rats. The diabetic-control animals displayed a lower weight of the muscles in the lower limb considered individually than the control rats and the diabetic plus C-peptide rats (P = 0.03; P = 0.03; P = 0.04; P = 0.004, respectively). The diabetic-control rats presented a significantly higher serum concentration of ubiquitin compared with the diabetic plus C-peptide and the control animals (P = 0.02 and P = 0.01). In muscles of the lower limb, the pAmpk expression was higher in the diabetic plus C-peptide than the diabetic-control rats (in the gastrocnemius, P = 0.002; in the tibialis anterior P = 0.005). The protein expression of Atrogin-1 in gastrocnemius and tibialis was lower in the diabetic plus C-peptide than in diabetic-control rats (P = 0.02, P = 0.03). After 42 days, the cross-sectional area in the gastrocnemius of the diabetic plus C-peptide group had been reduced by 6.6% while the diabetic-control rats had a 39.5% reduction compared with the control animals (P = 0.02). The cross-sectional area of the tibialis and the extensor digitorum longus muscles was reduced, in the diabetic plus C-peptide rats, by 10% and 11%, respectively, while the diabetic-control group had a reduction of 65% and 45% compared with the control animals (both P < 0.0001). Similar results were obtained for the minimum Feret's diameter and perimeter. ConclusionsC-peptide administration in rats could protect skeletal muscle mass from atrophy induced by type 1 diabetes mellitus. Our findings could suggest that targeting the ubiquitin-proteasome system, Ampk and muscle-specific E3 ubiquitin ligases such as Atrogin-1 and Traf6 may be an effective strategy for molecular and clinical intervention in the muscle wasting pathological process in T1DM.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Geriatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Geriatrics (hsv//eng)
Keyword
- C-peptide
- muscle mass
- type 1 diabetes
- atrophy
- muscle-specific E3
- ubiquitin ligase
- foxo transcription factors
- skeletal-muscle
- ubiquitin ligases
- body-composition
- atrophy
- metabolism
- activation
- expression
- glucose
- impact
- Geriatrics & Gerontology
- General & Internal Medicine
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Maurotti, S.
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Pujia, R.
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Galluccio, A.
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Nucera, S.
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Musolino, V.
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Mare, R.
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show more...
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Frosina, M.
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Noto, F. R.
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Mollace, V.
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Romeo, Stefano, ...
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Pujia, A.
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Montalcini, T.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Geriatrics
- Articles in the publication
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Journal of Cache ...
- By the university
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University of Gothenburg