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Differential control of muscle mass in type 1 and type 2 diabetes mellitus

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Abstract

Diabetes mellitus—whether driven by insulin deficiency or insulin resistance—causes major alterations in muscle metabolism. These alterations have an impact on nutrient handling, including the metabolism of glucose, lipids, and amino acids, and also on muscle mass and strength. However, the ways in which the distinct forms of diabetes affect muscle mass differ greatly. The most common forms of diabetes mellitus are type 1 and type 2. Thus, whereas type 1 diabetic subjects without insulin treatment display a dramatic loss of muscle, most type 2 diabetic subjects show no changes or even an increase in muscle mass. However, the most commonly used rodent models of type 2 diabetes are characterized by muscle atrophy and do not mimic the features of the disease in humans in terms of muscle mass. In this review, we analyze the processes that are differentially regulated under these forms of diabetes and propose regulatory mechanisms to explain them.

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Abbreviations

4EBP:

Eukaryotic translation initiation factor 4E-binding protein

AKT:

v-Akt murine thymoma viral oncogene homolog

Atg4b:

Autophagy-related protein 4b

Atg8:

Autophagy-related protein 8

Atg12:

Autophagy-related protein 12

ATP:

Adenosine triphosphate

BMI:

Body mass index

Bnip3:

BCL2/adenovirus E1B 19-kDa protein-interacting protein 3

Bnip3l:

BCL2/adenovirus E1B 19-kDa protein-interacting protein 3-like

DOR:

Diabetes and obesity regulated

EDL:

Extensor digitorum longus

eIF2B:

Eukaryotic translation initiation factor 2B

eIF4E:

Eukaryotic translation initiation factor 4E

FoxO:

Forkhead box O

GABARAP:

Gamma-aminobutyric acid receptor-associated protein

GABARAPL1:

Gamma-aminobutyric acid receptor-associated protein-like 1

GATE16:

Golgi-associated ATPase enhancer of 16 kDa

GR:

Glucocorticoid receptor

GSK3β:

Glycogen synthase kinase 3 beta

GTP:

Guanosine triphosphate

IGF-1:

Insulin-like growth factor-1

IL-6:

Interleukin-6

IRS:

Insulin receptor substrate

LC3:

Microtubule-associated protein 1 light chain 3

Lep:

Leptin

Lepr:

Leptin receptor

MuRF1:

Muscle RING finger 1

mTOR:

Mammalian target of rapamycin

mTORC1:

Mammalian target of rapamycin complex 1

mTORC2:

Mammalian target of rapamycin complex 2

PDK1:

3-Phosphoinositide-dependent protein kinase-1

PI3K:

Phosphatidylinositol 3-kinase

PML:

Promyelocytic leukemia

PPARγ:

Peroxisome proliferator-activated receptor gamma

Rheb:

Ras homolog enriched in brain

STAT3:

Signal transducer and activator of transcription 3

S6:

Ribosomal protein S6

S6K1:

Ribosomal protein S6 kinase 1

S6K2:

Ribosomal protein S6 kinase 2

TNFα:

Tumor necrosis factor α

TP53INP1:

Tumor protein p53-inducible nuclear protein 1

TP53INP2:

Tumor protein p53-inducible nuclear protein 2

TRα1:

Thyroid hormone receptor alpha large isoform

TSC1:

Tuberous sclerosis complex 1

TSC2:

Tuberous sclerosis complex 2

ULK1:

Unc-51-like autophagy-activating kinase 1

UPS:

Ubiquitin proteasome system

Vps34:

Phosphatidylinositol 3-kinase Vps34

VDR:

Vitamin D3 receptor

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Acknowledgments

We would like to thank Ms. Tanya Yates for editorial support. D. S. was a recipient of a FPU fellowship from the “Ministerio de Educación y Cultura”, Spain, and currently holds a California Institute for Regenerative Medicine (CIRM) Training grant (TG2-01162). This work was supported by research grants from the MINECO (SAF2008-03803 and SAF2013-40987R), grants 2009SGR915 and 2014SGR48 from the “Generalitat de Catalunya”, CIBERDEM (“Instituto de Salud Carlos III”), INTERREG IV-B-SUDOE-FEDER (DIOMED, SOE1/P1/E178), and DEXLIFE (Grant agreement no: 279228). A. Z. is recipient of an ICREA Acadèmia (“Generalitat de Catalunya”).

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Authors and Affiliations

  1. Development, Aging and Regeneration Program (DARe), Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Rd, La Jolla, CA, 92037, USA

    David Sala

  2. Institute for Research in Biomedicine (IRB Barcelona), C/Baldiri Reixac 10, 08028, Barcelona, Spain

    Antonio Zorzano

  3. Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal 645, 08028, Barcelona, Spain

    Antonio Zorzano

  4. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain

    Antonio Zorzano

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  1. David Sala
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Sala, D., Zorzano, A. Differential control of muscle mass in type 1 and type 2 diabetes mellitus. Cell. Mol. Life Sci. 72, 3803–3817 (2015). https://doi.org/10.1007/s00018-015-1954-7

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  • DOI: https://doi.org/10.1007/s00018-015-1954-7

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