open access

Vol 71, No 5 (2020)
Original paper
Submitted: 2020-03-22
Accepted: 2020-07-24
Published online: 2020-08-13
Get Citation

Serum level of A-kinase anchoring protein 1, negatively correlated with insulin resistance and body mass index, decreases slightly in patients with newly diagnosed T2DM

Haifeng Zhu1, Xingbo Cheng1, Qingtao Fan1
·
Pubmed: 32797476
·
Endokrynol Pol 2020;71(5):411-417.
Affiliations
  1. Department of Endocrinology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, Suzhou, China

open access

Vol 71, No 5 (2020)
Original Paper
Submitted: 2020-03-22
Accepted: 2020-07-24
Published online: 2020-08-13

Abstract

Introduction: At present, the number of people suffering from diabetes and obesity is increasing in China, and also all over the world. Researchers found that decreased expression of A-kinase anchoring protein 1 (AKAP1), which was thought to regulate the function and structure of mitochondria, might be related to these two diseases. However, as far as we know, there is no study about the changes of serum AKAP1 protein in these two diseases. Hence we conducted this experiment to study the relationship between serum levels of AKAP1 with T2DM and obesity.

Material and methods: There were 261 subjects involved in the experiment, including 130 patients with newly diagnosed T2DM and 131 individuals with normal glucose tolerance (NGT). They were further divided into four groups as follows. Subjects with NGT and normal weight (NW) were assigned to the NGT+NW group, those with NGT but with overweight (OW) or obesity (OB) were assigned to the NGT+OW/OB group, and so on; the rest were divided into the T2DM+NW group and the T2DM+OW/OB group. Serum AKAP1 levels were tested by ELISA method and compared by T-test. Linear regression was applied to discuss independent factors of AKAP1. Multiple logistic regression was used to analyse the relationship between AKAP1 and the prevalence of T2DM.

Results: Serum AKAP1 in the NGT+NW group was 1.74 ± 0.42 ng/mL, higher than that in the NGT+OW/OB group, at 1.59 ± 0.41 ng/mL (t = 2.114, p = 0.036), and the T2DM+OW/OB group, at 1.52 ± 0.36 ng/ml (t = 3.219, p = 0.002). A-kinase anchoring protein 1 in 130 subjects with T2DM was lower than that in subjects with NGT, 1.57 ± 0.35 ng/mL vs. 1.67 ± 0.42 ng/mL, t = 2.036, p = 0.043. Liner regression showed that insulin resistance (IR) and body mass index (BMI) were independent factors negatively related to AKAP1: b = –0.019 and –0.032, respectively. Compared to the highest tertile of AKAP1, the prevalence of T2DM was higher in the other two tertiles; OR was 2.207 (1.203, 4.050) and 2.051 (1.121, 3.753), respectively. Conclusions: Serum AKAP1 level decreases slightly in patients with T2DM and obesity. Subjects with lower leve1s of serum AKAP1 are susceptible to T2DM. 

Abstract

Introduction: At present, the number of people suffering from diabetes and obesity is increasing in China, and also all over the world. Researchers found that decreased expression of A-kinase anchoring protein 1 (AKAP1), which was thought to regulate the function and structure of mitochondria, might be related to these two diseases. However, as far as we know, there is no study about the changes of serum AKAP1 protein in these two diseases. Hence we conducted this experiment to study the relationship between serum levels of AKAP1 with T2DM and obesity.

Material and methods: There were 261 subjects involved in the experiment, including 130 patients with newly diagnosed T2DM and 131 individuals with normal glucose tolerance (NGT). They were further divided into four groups as follows. Subjects with NGT and normal weight (NW) were assigned to the NGT+NW group, those with NGT but with overweight (OW) or obesity (OB) were assigned to the NGT+OW/OB group, and so on; the rest were divided into the T2DM+NW group and the T2DM+OW/OB group. Serum AKAP1 levels were tested by ELISA method and compared by T-test. Linear regression was applied to discuss independent factors of AKAP1. Multiple logistic regression was used to analyse the relationship between AKAP1 and the prevalence of T2DM.

Results: Serum AKAP1 in the NGT+NW group was 1.74 ± 0.42 ng/mL, higher than that in the NGT+OW/OB group, at 1.59 ± 0.41 ng/mL (t = 2.114, p = 0.036), and the T2DM+OW/OB group, at 1.52 ± 0.36 ng/ml (t = 3.219, p = 0.002). A-kinase anchoring protein 1 in 130 subjects with T2DM was lower than that in subjects with NGT, 1.57 ± 0.35 ng/mL vs. 1.67 ± 0.42 ng/mL, t = 2.036, p = 0.043. Liner regression showed that insulin resistance (IR) and body mass index (BMI) were independent factors negatively related to AKAP1: b = –0.019 and –0.032, respectively. Compared to the highest tertile of AKAP1, the prevalence of T2DM was higher in the other two tertiles; OR was 2.207 (1.203, 4.050) and 2.051 (1.121, 3.753), respectively. Conclusions: Serum AKAP1 level decreases slightly in patients with T2DM and obesity. Subjects with lower leve1s of serum AKAP1 are susceptible to T2DM. 

Get Citation

Keywords

A-kinase anchoring protein 1; type 2 diabetes mellitus; obesity

About this article
Title

Serum level of A-kinase anchoring protein 1, negatively correlated with insulin resistance and body mass index, decreases slightly in patients with newly diagnosed T2DM

Journal

Endokrynologia Polska

Issue

Vol 71, No 5 (2020)

Article type

Original paper

Pages

411-417

Published online

2020-08-13

Page views

1638

Article views/downloads

562

DOI

10.5603/EP.a2020.0051

Pubmed

32797476

Bibliographic record

Endokrynol Pol 2020;71(5):411-417.

Keywords

A-kinase anchoring protein 1
type 2 diabetes mellitus
obesity

Authors

Haifeng Zhu
Xingbo Cheng
Qingtao Fan

References (27)
  1. Cho NH, Shaw JE, Karuranga S, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018; 138: 271–281.
  2. NCD Risk Factor Collaboration. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet. 2016; 387(10026): 1377–1396.
  3. Pinti MV, Fink GK, Hathaway QA, et al. Mitochondrial dysfunction in type 2 diabetes mellitus: an organ-based analysis. Am J Physiol Endocrinol Metab. 2019; 316(2): E268–E285.
  4. Liu Y, Merrill RA, Strack S. A-Kinase Anchoring Protein 1: Emerging Roles in Regulating Mitochondrial Form and Function in Health and Disease. Cells. 2020; 9(2).
  5. Rodriguez-Cuenca S, Carobbio S, Velagapudi VR, et al. Peroxisome proliferator-activated receptor γ-dependent regulation of lipolytic nodes and metabolic flexibility. Mol Cell Biol. 2012; 32(8): 1555–1565.
  6. Marrades MP, González-Muniesa P, Martínez JA, et al. A dysregulation in CES1, APOE and other lipid metabolism-related genes is associated to cardiovascular risk factors linked to obesity. Obes Facts. 2010; 3(5): 312–318.
  7. Liu FZ, Ji LL, Li F. Preliminary study on the role of AKAP1 in the development of diabetes mellitus. J Am Coll Cardiol. 2017; 70(16): C56–C57.
  8. Zhang W, Sakoda H, Nakazato M. Neuromedin U suppresses insulin secretion by triggering mitochondrial dysfunction and endoplasmic reticulum stress in pancreatic β-cells. FASEB J. 2020; 34(1): 133–147.
  9. Sas K, Szabó E, Vécsei L. Mitochondria, Oxidative Stress and the Kynurenine System, with a Focus on Ageing and Neuroprotection. Molecules. 2018; 23(1).
  10. De Rasmo D, Signorile A, Larizza M, et al. Activation of the cAMP cascade in human fibroblast cultures rescues the activity of oxidatively damaged complex I. Free Radic Biol Med. 2012; 52(4): 757–764.
  11. Livigni A, Scorziello A, Agnese S, et al. Mitochondrial AKAP121 links cAMP and src signaling to oxidative metabolism. Mol Biol Cell. 2006; 17(1): 263–271.
  12. Aggarwal S, Gabrovsek L, Langeberg LK, et al. Depletion of dAKAP1-protein kinase A signaling islands from the outer mitochondrial membrane alters breast cancer cell metabolism and motility. J Biol Chem. 2019; 294(9): 3152–3168.
  13. Perrino C, Feliciello A, Schiattarella GG, et al. AKAP121 downregulation impairs protective cAMP signals, promotes mitochondrial dysfunction, and increases oxidative stress. Cardiovasc Res. 2010; 88(1): 101–110.
  14. Kuo T, Chen TC, Lee RA, et al. Pik3r1 Is Required for Glucocorticoid-Induced Perilipin 1 Phosphorylation in Lipid Droplet for Adipocyte Lipolysis. Diabetes. 2017; 66(6): 1601–1610.
  15. Planas JV, Cummings DE, Idzerda RL, et al. Mutation of the RIIbeta subunit of protein kinase A differentially affects lipolysis but not gene induction in white adipose tissue. J Biol Chem. 1999; 274(51): 36281–36287.
  16. Bridges D, MacDonald JA, Wadzinski B, et al. Identification and characterization of D-AKAP1 as a major adipocyte PKA and PP1 binding protein. Biochem Biophys Res Commun. 2006; 346(1): 351–357.
  17. Schiattarella GG, Cattaneo F, Pironti G, et al. Akap1 Deficiency Promotes Mitochondrial Aberrations and Exacerbates Cardiac Injury Following Permanent Coronary Ligation via Enhanced Mitophagy and Apoptosis. PLoS One. 2016; 11(5): e0154076.
  18. Marin W. A-kinase anchoring protein 1 (AKAP1) and its role in some cardiovascular diseases. J Mol Cell Cardiol. 2020; 138: 99–109.
  19. Schiattarella GG, Cattaneo F, Carrizzo A, et al. Regulates Vascular Function and Endothelial Cells Behavior. Hypertension. 2018; 71(3): 507–517.
  20. Cattaneo F, Schiattarella GG, Paolillo R, et al. AKAP1 modulates endothelial cells function, arterial systolic blood pressure. Eur Heart J. 2017; 38 Suppl 1(52).
  21. Heijnen HFG, Waaijenborg S, Crapo JD, et al. Colocalization of eNOS and the catalytic subunit of PKA in endothelial cell junctions: a clue for regulated NO production. J Histochem Cytochem. 2004; 52(10): 1277–1285.
  22. Rinaldi L, Sepe M, Delle Donne R, et al. Mitochondrial AKAP1 supports mTOR pathway and tumor growth. Cell Death Dis. 2017; 8(6): e2842.
  23. Jefcoate C, Larsen M. StAR, a bridge from ApoE, LDL, and HDL cholesterol trafficking to mitochondrial metabolism. Curr Opin Endocrinol Metab Res. 2019; 8: 195–205.
  24. Dyson MT, Jones JK, Kowalewski MP, et al. Mitochondrial A-kinase anchoring protein 121 binds type II protein kinase A and enhances steroidogenic acute regulatory protein-mediated steroidogenesis in MA-10 mouse leydig tumor cells. Biol Reprod. 2008; 78(2): 267–277.
  25. Park SJ, Lee SuB, Suh Y, et al. DISC1 Modulates Neuronal Stress Responses by Gate-Keeping ER-Mitochondria Ca Transfer through the MAM. Cell Rep. 2017; 21(10): 2748–2759.
  26. Wang Q, Zhang M, Torres G, et al. Metformin Suppresses Diabetes-Accelerated Atherosclerosis via the Inhibition of Drp1-Mediated Mitochondrial Fission. Diabetes. 2017; 66(1): 193–205.
  27. Wang Yu, An H, Liu T, et al. Metformin Improves Mitochondrial Respiratory Activity through Activation of AMPK. Cell Rep. 2019; 29(6): 1511–1523.e5.

Regulations

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 jest  VM Media Group sp. z o.o., Grupa Via Medica, ul. Świętokrzyska 73, 80–180 Gdańsk

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