Nuclear lamins and diabetes mellitus

  • Wei Xie Laboratory of Nuclear Dynamics and Architecture, Skin Research Institute of Singapore (SRIS), Agency for Science, Technology and Research (A*STAR), Singapore
  • Brian Burke Laboratory of Nuclear Dynamics and Architecture, Skin Research Institute of Singapore (SRIS), Agency for Science, Technology and Research (A*STAR), Singapore
Keywords: Lamins, Diabetes mellitus, Nuclear lamina, Laminopathy, Dunnigan type familial partial lipodystrophy

Abstract

In metazoans, a thin filamentous network referred to as the nuclear lamina plays an essential role in providing mechanical support to the nucleus. The major constituent of the nuclear lamina is type V intermediate filament proteins that are collectively referred to as lamins. A variety of diseases collectively termed laminopathies have been linked to mutations in genes encoding nuclear envelope proteins, in particular lamins, such as X-linked Emery Dreifus muscular dystrophy, dilated cardiomyopathy, Dunnigan type familial partial lipodystrophy and Hutchinson-Gilford progeria syndrome. Apart from laminopathies, genome-wide association studies have also been implicated nuclear lamins in the pathophysiology of type 2 diabetes mellitus, although little information in terms of the function of lamins in its pathogenesis. Our current review attempts to summarize risk factors of diabetes mellitus that could be attributable to lamin mutations and indirectly linked to lamin-associated factors identified in the last two decades.

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References

Romero-Bueno R, de la Cruz Ruiz P, Artal-Sanz M, Askjaer P, Dobrzynska A. Nuclear organization in stress and aging. Cells. 2019;8(7).

Xie W, Burke B. Nuclear networking. Nucleus. 2017;8(4):323-30.

Polychronidou M, Grobhans J. Determining nuclear shape: the role of farnesylated nuclear membrane proteins. Nucleus. 2011;2(1):17-23.

Harr JC, Luperchio TR, Wong X, Cohen E, Wheelan SJ, Reddy KL. Directed targeting of chromatin to the nuclear lamina is mediated by chromatin state and A-type lamins. J Cell Biol. 2015;208(1):33-52.

Butin-Israeli V, Adam SA, Jain N, Otte GL, Neems D, Wiesmuller L, et al. Role of lamin b1 in chromatin instability. Mol Cell Biol. 2015;35(5):884-98.

Butin-Israeli V, Adam SA, Goldman RD. Regulation of nucleotide excision repair by nuclear lamin b1. PLoS One. 2013;8(7):e69169.

Earle AJ, Kirby TJ, Fedorchak GR, Isermann P, Patel J, Iruvanti S, et al. Mutant lamins cause nuclear envelope rupture and DNA damage in skeletal muscle cells. Nat Mater. 2020;19(4):464-73.

Xie W, Burke B. Lamins. Curr Biol. 2016;26(9):R348-50.

Burke B, Stewart CL. The nuclear lamins: flexibility in function. Nat Rev Mol Cell Biol. 2013;14(1):13-24.

Dechat T, Adam SA, Taimen P, Shimi T, Goldman RD. Nuclear lamins. Cold Spring Harb Perspect Biol. 2010;2(11):a000547.

Worman HJ. Nuclear lamins and laminopathies. J Pathol. 2012;226(2):316-25.

Wu Y, Ding Y, Tanaka Y, Zhang W. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int J Med Sci. 2014;11(11):1185-200.

Tripathi BK, Srivastava AK. Diabetes mellitus: complications and therapeutics. Med Sci Monit. 2006;12(7):RA130-47.

Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus--present and future perspectives. Nat Rev Endocrinol. 2011;8(4):228-36.

Thomas PPM, Alshehri SM, van Kranen HJ, Ambrosino E. The impact of personalized medicine of Type 2 diabetes mellitus in the global health context. Per Med. 2016;13(4):381-93.

Hegele RA. Familial partial lipodystrophy: a monogenic form of the insulin resistance syndrome. Mol Genet Metab. 2000;71(4):539-44.

Bonne G, Mercuri E, Muchir A, Urtizberea A, Becane HM, Recan D, et al. Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene. Ann Neurol. 2000;48(2):170-80.

Cao H, Hegele RA. Nuclear lamin A/C R482Q mutation in canadian kindreds with Dunnigan-type familial partial lipodystrophy. Hum Mol Genet. 2000;9(1):109-12.

Garg A, Vinaitheerthan M, Weatherall PT, Bowcock AM. Phenotypic heterogeneity in patients with familial partial lipodystrophy (dunnigan variety) related to the site of missense mutations in lamin a/c gene. J Clin Endocrinol Metab. 2001;86(1):59-65.

Vigouroux C, Magre J, Vantyghem MC, Bourut C, Lascols O, Shackleton S, et al. Lamin A/C gene: sex-determined expression of mutations in Dunnigan-type familial partial lipodystrophy and absence of coding mutations in congenital and acquired generalized lipoatrophy. Diabetes. 2000;49(11):1958-62.

Hegele RA, Cao H, Anderson CM, Hramiak IM. Heterogeneity of nuclear lamin A mutations in Dunnigan-type familial partial lipodystrophy. J Clin Endocrinol Metab. 2000;85(9):3431-5.

Morris GE, Manilal S. Heart to heart: from nuclear proteins to Emery-Dreifuss muscular dystrophy. Hum Mol Genet. 1999;8(10):1847-51.

Flier JS. Pushing the envelope on lipodystrophy. Nat Genet. 2000;24(2):103-4.

Hegele RA, Cao H, Huff MW, Anderson CM. LMNA R482Q mutation in partial lipodystrophy associated with reduced plasma leptin concentration. J Clin Endocrinol Metab. 2000;85(9):3089-93.

Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018;98(4):2133-223.

Unger RH, Zhou YT, Orci L. Regulation of fatty acid homeostasis in cells: novel role of leptin. Proc Natl Acad Sci U S A. 1999;96(5):2327-32.

Randle PJ. Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab Rev. 1998;14(4):263-83.

Shulman GI. Cellular mechanisms of insulin resistance in humans. Am J Cardiol. 1999;84(1A):3J-10J.

Caux F, Dubosclard E, Lascols O, Buendia B, Chazouilleres O, Cohen A, et al. A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy. J Clin Endocrinol Metab. 2003;88(3):1006-13.

Young J, Morbois-Trabut L, Couzinet B, Lascols O, Dion E, Bereziat V, et al. Type A insulin resistance syndrome revealing a novel lamin A mutation. Diabetes. 2005;54(6):1873-8.

Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536(7616):285-91.

Florwick A, Dharmaraj T, Jurgens J, Valle D, Wilson KL. LMNA sequences of 60,706 unrelated individuals reveal 132 novel missense variants in A-type lamins and suggest a link between variant p.G602S and type 2 diabetes. Front Genet. 2017;8:79.

de Toledo M, Lopez-Mejia IC, Cavelier P, Pratlong M, Barrachina C, Gromada X, et al. Lamin C counteracts glucose intolerance in aging, obesity, and diabetes through beta-cell adaptation. Diabetes. 2020;69(4):647-60.

Miranda M, Chacon MR, Gutierrez C, Vilarrasa N, Gomez JM, Caubet E, et al. LMNA mRNA expression is altered in human obesity and type 2 diabetes. Obesity (Silver Spring). 2008;16(8):1742-8.

Rodriguez-Acebes S, Palacios N, Botella-Carretero JI, Olea N, Crespo L, Peromingo R, et al. Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: distinct expression of cell-cycle- and differentiation-related genes. BMC Med Genomics. 2010;3:61.

Nadeau M, Noel S, Laberge PY, Hurtubise J, Tchernof A. Adipose tissue lamin A/C messenger RNA expression in women. Metabolism. 2010;59(8):1106-14.

Kim Y, Bayona PW, Kim M, Chang J, Hong S, Park Y, et al. Macrophage lamin A/C regulates inflammation and the development of obesity-induced insulin resistance. Front Immunol. 2018;9:696.

Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116(1):39-48.

Ledoux S, Queguiner I, Msika S, Calderari S, Rufat P, Gasc JM, et al. Angiogenesis associated with visceral and subcutaneous adipose tissue in severe human obesity. Diabetes. 2008;57(12):3247-57.

Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev. 2010;11(1):11-8.

Lee BC, Kim MS, Pae M, Yamamoto Y, Eberle D, Shimada T, et al. Adipose natural killer cells regulate adipose tissue macrophages to promote insulin resistance in obesity. Cell Metab. 2016;23(4):685-98.

Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes. 2008;57(12):3239-46.

Li P, Lu M, Nguyen MT, Bae EJ, Chapman J, Feng D, et al. Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice. J Biol Chem. 2010;285(20):15333-45.

Kratz M, Coats BR, Hisert KB, Hagman D, Mutskov V, Peris E, et al. Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Cell Metab. 2014;20(4):614-25.

Jeong K, Kwon H, Lee J, Jang D, Pak Y. Insulin-response epigenetic activation of Egr-1 and JunB genes at the nuclear periphery by A-type lamin-associated pY19-Caveolin-2 in the inner nuclear membrane. Nucleic Acids Res. 2015;43(6):3114-27.

Kwon H, Lee J, Jeong K, Jang D, Choi M, Pak Y. A-type lamin-dependent homo-oligomerization for pY19-Caveolin-2 to function as an insulin-response epigenetic regulator. Biochim Biophys Acta. 2016;1863(11):2681-9.

Parton RG, del Pozo MA. Caveolae as plasma membrane sensors, protectors and organizers. Nat Rev Mol Cell Biol. 2013;14(2):98-112.

Kwon H, Jeong K, Hwang EM, Park JY, Pak Y. A novel domain of caveolin-2 that controls nuclear targeting: regulation of insulin-specific ERK activation and nuclear translocation by caveolin-2. J Cell Mol Med. 2011;15(4):888-908.

Kwon H, Jeong K, Hwang EM, Park JY, Hong SG, Choi WS, et al. Caveolin-2 regulation of STAT3 transcriptional activation in response to insulin. Biochim Biophys Acta. 2009;1793(7):1325-33.

Jeong K, Kwon H, Lee J, Jang D, Hwang EM, Park JY, et al. Rab6-mediated retrograde transport regulates inner nuclear membrane targeting of caveolin-2 in response to insulin. Traffic. 2012;13(9):1218-33.

Elenbaas JS, Bragazzi Cunha J, Azuero-Dajud R, Nelson B, Oral EA, Williams JA, et al. Lamin A/C maintains exocrine pancreas homeostasis by regulating stability of RB and activity of E2F. Gastroenterology. 2018;154(6):1625-9 e8.

Johnson BR, Nitta RT, Frock RL, Mounkes L, Barbie DA, Stewart CL, et al. A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation. Proc Natl Acad Sci U S A. 2004;101(26):9677-82.

Iglesias A, Murga M, Laresgoiti U, Skoudy A, Bernales I, Fullaondo A, et al. Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice. J Clin Invest. 2004;113(10):1398-407.

Hansen JB, Jorgensen C, Petersen RK, Hallenborg P, De Matteis R, Boye HA, et al. Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation. Proc Natl Acad Sci U S A. 2004;101(12):4112-7.

Denechaud PD, Lopez-Mejia IC, Giralt A, Lai Q, Blanchet E, Delacuisine B, et al. E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis. J Clin Invest. 2016;126(1):137-50.

Published
2020-12-22
How to Cite
XieW., & BurkeB. (2020). Nuclear lamins and diabetes mellitus. STEMedicine, 2(5), e73. https://doi.org/10.37175/stemedicine.v2i5.73
Section
Review articles