open access

Vol 71, No 1 (2020)
Original Paper
Published online: 2019-11-15
Submitted: 2019-06-20
Accepted: 2019-10-29
Get Citation

Assessment of the association of serum progranulin with autophagy in diabetic patients

Nahla S. Hassan, Nievien A. Mahran, Marwa G.A. Hegazy
DOI: 10.5603/EP.a2019.0056
·
Endokrynologia Polska 2020;71(1):51-57.

open access

Vol 71, No 1 (2020)
Original Paper
Published online: 2019-11-15
Submitted: 2019-06-20
Accepted: 2019-10-29

Abstract

Introduction: Progranulin (PGRN) has newly arisen as an important regulatory protein of glucose metabolism and insulin sensitivity. Progranulin expression is interrelated with lysosomal function strongly linked to autophagy pathway. We aimed to evaluate the correlation between PGRN protein and microtubule-associated protein light chain 3B (LC3B) expression level in diabetic patients. Material and methods: Blood samples of 70 type 2 diabetic Egyptian patients were provided for analysis of concentrations of serum progranulin and interleukin 6 (IL-6) using ELISA, and quantifying expression of LC3B RNA level using qPCR. A group of 20 healthy volunteers were also enrolled. Results: Serum levels of PGRN and IL-6 as well as LC3B gene expression levels were markedly higher in type 2 diabetic patients. Additionally, our study revealed a cut-off value of 18.14 ng/mL for progranulin serum level and 3.23 for LC3B expression level, with sensitivities of 83.6% and 75.4% and specificities of 83.8% and 58.3%, respectively. Circulating PGRN levels are positively correlated with body mass index (BMI), glucose concentration, and IL-6. Conclusion: Our results support the hypothesis that progranulin is introduced as a novel marker of chronic inflammatory response in type 2 diabetes that aggravates insulin resistance via activated autophagy, indicating the importance of this novel adipokine in the regulation of glucose metabolism and as a promising therapeutic target in the treatment of diabetes. Key words: diabetes; progranulin; autophagy; microtubule-associated proteins light chain 3B; interleukin 6

Abstract

Introduction: Progranulin (PGRN) has newly arisen as an important regulatory protein of glucose metabolism and insulin sensitivity. Progranulin expression is interrelated with lysosomal function strongly linked to autophagy pathway. We aimed to evaluate the correlation between PGRN protein and microtubule-associated protein light chain 3B (LC3B) expression level in diabetic patients. Material and methods: Blood samples of 70 type 2 diabetic Egyptian patients were provided for analysis of concentrations of serum progranulin and interleukin 6 (IL-6) using ELISA, and quantifying expression of LC3B RNA level using qPCR. A group of 20 healthy volunteers were also enrolled. Results: Serum levels of PGRN and IL-6 as well as LC3B gene expression levels were markedly higher in type 2 diabetic patients. Additionally, our study revealed a cut-off value of 18.14 ng/mL for progranulin serum level and 3.23 for LC3B expression level, with sensitivities of 83.6% and 75.4% and specificities of 83.8% and 58.3%, respectively. Circulating PGRN levels are positively correlated with body mass index (BMI), glucose concentration, and IL-6. Conclusion: Our results support the hypothesis that progranulin is introduced as a novel marker of chronic inflammatory response in type 2 diabetes that aggravates insulin resistance via activated autophagy, indicating the importance of this novel adipokine in the regulation of glucose metabolism and as a promising therapeutic target in the treatment of diabetes. Key words: diabetes; progranulin; autophagy; microtubule-associated proteins light chain 3B; interleukin 6

Get Citation

Keywords

diabetes; progranulin; autophagy; microtubule-associated proteins light chain 3B; interleukin 6

About this article
Title

Assessment of the association of serum progranulin with autophagy in diabetic patients

Journal

Endokrynologia Polska

Issue

Vol 71, No 1 (2020)

Pages

51-57

Published online

2019-11-15

DOI

10.5603/EP.a2019.0056

Bibliographic record

Endokrynologia Polska 2020;71(1):51-57.

Keywords

diabetes
progranulin
autophagy
microtubule-associated proteins light chain 3B
interleukin 6

Authors

Nahla S. Hassan
Nievien A. Mahran
Marwa G.A. Hegazy

References (32)
  1. He Z, Bateman A. Progranulin (granulin-epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis. J Mol Med (Berl). 2003; 81(10): 600–612.
  2. Zhou J, Gao G, Crabb JW, et al. Purification of an autocrine growth factor homologous with mouse epithelin precursor from a highly tumorigenic cell line. J Biol Chem. 1993; 268(15): 10863–10869.
  3. Nguyen AD, Nguyen TA, Martens LH, et al. Progranulin: at the interface of neurodegenerative and metabolic diseases. Trends Endocrinol Metab. 2013; 24(12): 597–606.
  4. Kessenbrock K, Fröhlich L, Sixt M, et al. Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin. J Clin Invest. 2008; 118(7): 2438–2447.
  5. Zhou Bo, Li H, Liu J, et al. Progranulin induces adipose insulin resistance and autophagic imbalance via TNFR1 in mice. J Mol Endocrinol. 2015; 55(3): 231–243.
  6. Youn BS, Bang SI, Klöting N, et al. Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue. Diabetes. 2009; 58(3): 627–636.
  7. Qu H, Deng H, Hu Z. Plasma progranulin concentrations are increased in patients with type 2 diabetes and obesity and correlated with insulin resistance. Mediators Inflamm. 2013; 2013: 360190.
  8. Tang W, Lu Yi, Tian QY, et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science. 2011; 332(6028): 478–484.
  9. Langenberg C, Sharp SJ, Schulze MB, et al. InterAct Consortium. Long-term risk of incident type 2 diabetes and measures of overall and regional obesity: the EPIC-InterAct case-cohort study. PLoS Med. 2012; 9(6): e1001230.
  10. Matsubara T, Mita A, Minami K, et al. PGRN is a key adipokine mediating high fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue. Cell Metab. 2012; 15(1): 38–50.
  11. Liu J, Li H, Zhou Bo, et al. PGRN induces impaired insulin sensitivity and defective autophagy in hepatic insulin resistance. Mol Endocrinol. 2015; 29(4): 528–541.
  12. Jansen HJ, van Essen P, Koenen T, et al. Autophagy activity is up-regulated in adipose tissue of obese individuals and modulates proinflammatory cytokine expression. Endocrinology. 2012; 153(12): 5866–5874.
  13. Bugliani M, Mossuto S, Grano F, et al. Modulation of Autophagy Influences the Function and Survival of Human Pancreatic Beta Cells Under Endoplasmic Reticulum Stress Conditions and in Type 2 Diabetes. Front Endocrinol (Lausanne). 2019; 10: 52.
  14. Lum JJ, Bauer DE, Kong M, et al. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell. 2005; 120(2): 237–248.
  15. Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000; 19(21): 5720–5728.
  16. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008; 3(6): 1101–1108.
  17. Li H, Zhou Bo, Xu L, et al. Circulating PGRN is significantly associated with systemic insulin sensitivity and autophagic activity in metabolic syndrome. Endocrinology. 2014; 155(9): 3493–3507.
  18. Dunmore SJ, Brown JEP. The role of adipokines in β-cell failure of type 2 diabetes. J Endocrinol. 2013; 216(1): T37–T45.
  19. Bergmann K, Sypniewska G. Diabetes as a complication of adipose tissue dysfunction. Is there a role for potential new biomarkers? Clin Chem Lab Med. 2013; 51(1): 177–185.
  20. Tönjes A, Fasshauer M, Kratzsch J, et al. Adipokine pattern in subjects with impaired fasting glucose and impaired glucose tolerance in comparison to normal glucose tolerance and diabetes. PLoS One. 2010; 5(11): e13911.
  21. Waki H, Tontonoz P. Endocrine functions of adipose tissue. Annu Rev Pathol. 2007; 2: 31–56.
  22. Xu L, Zhou Bo, Li H, et al. Serum Levels of Progranulin Are Closely Associated with Microvascular Complication in Type 2 Diabetes. Dis Markers. 2015; 2015: 357279.
  23. Eriksen JL, Mackenzie IRA. Progranulin: normal function and role in neurodegeneration. J Neurochem. 2008; 104(2): 287–297.
  24. Liu CJ, Bosch X. Progranulin: a growth factor, a novel TNFR ligand and a drug target. Pharmacol Ther. 2012; 133(1): 124–132.
  25. Klöting N, Fasshauer M, Dietrich A, et al. Insulin-sensitive obesity. Am J Physiol Endocrinol Metab. 2010; 299(3): E506–E515.
  26. Guo Q, Xu L, Li H, et al. Progranulin causes adipose insulin resistance via increased autophagy resulting from activated oxidative stress and endoplasmic reticulum stress. Lipids Health Dis. 2017; 16(1): 25.
  27. Crişan TO, Plantinga TS, van de Veerdonk FL, et al. Inflammasome-independent modulation of cytokine response by autophagy in human cells. PLoS One. 2011; 6(4): e18666.
  28. Kawasaki N, Asada R, Saito A, et al. Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue. Sci Rep. 2012; 2: 799.
  29. Linnemann AK, Blumer J, Marasco MR, et al. Interleukin 6 protects pancreatic β cells from apoptosis by stimulation of autophagy. FASEB J. 2017; 31(9): 4140–4152.
  30. Grumati P, Coletto L, Schiavinato A, et al. Physical exercise stimulates autophagy in normal skeletal muscles but is detrimental for collagen VI-deficient muscles. Autophagy. 2011; 7(12): 1415–1423.
  31. Paula-Gomes S, Gonçalves DAP, Baviera AM, et al. Insulin suppresses atrophy- and autophagy-related genes in heart tissue and cardiomyocytes through AKT/FOXO signaling. Horm Metab Res. 2013; 45(12): 849–855.
  32. Su Y, Wu J, He J, et al. High insulin impaired ovarian function in early pregnant mice and the role of autophagy in this process. Endocr J. 2017; 64(6): 613–621.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Via MedicaWydawcą serwisu jest  "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl