Skip to main content
Erschienen in: Acta Diabetologica 1/2011

01.03.2011 | Original Article

Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study

verfasst von: Lei Kong, Junjie Zhu, Wenxia Han, Xiuyun Jiang, Min Xu, Yue Zhao, Qiongzhu Dong, Zengfen Pang, Qingbo Guan, Ling Gao, Jiajun Zhao, Lei Zhao

Erschienen in: Acta Diabetologica | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

To explore the clinical significance of seven diabetes-related serum microRNAs (miR-9, miR-29a, miR-30d, miR34a, miR-124a, miR146a and miR375) during the pathogenesis of type 2 diabetes (T2D), 56 subjects were recruited to this study: 18 cases of newly diagnosed T2D (n-T2D) patients, 19 cases of pre-diabetes individuals (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]) and 19 cases of T2D-susceptible individuals with normal glucose tolerance (s-NGT). Serum miRNAs were determined by real-time RT-PCR. Expression levels of single miRNAs and the expression signatures of miRNAs as a panel were analysed among the three groups. In n-T2D, all 7 miRNAs were significantly up-regulated compared with s-NGT and five were significantly up-regulated compared with pre-diabetes, while miRNA expression was not significantly different between s-NGT and pre-diabetes. By Canonical discriminant analysis, 70.6% of n-T2D subjects (12/17) were recognized by canonical discriminant function, while s-NGT and pre-diabetes subjects could not be discriminated from each other. Similar results were found in Hierarchical Clustering analysis based on the expression levels of all seven miRNAs. In different statistical analysis, miR-34a always showed the most significant differences. We conclude that the expression levels of seven diabetes-related miRNAs in serum were significantly elevated in n-T2D compared with pre-diabetes and/or s-NGT, and the latter two groups featured similar expression patterns of these miRNAs, suggesting that during the pathogenesis of T2D, the peripheral diabetes-related miRNAs have not changed significantly from s-NGT at pre-diabetic stage.
Literatur
1.
Zurück zum Zitat Wild S, Roglic G, Green A et al (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053PubMedCrossRef Wild S, Roglic G, Green A et al (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053PubMedCrossRef
2.
Zurück zum Zitat Prentki M, Nolan CJ (2006) Islet beta cell failure in type 2 diabetes. J Clin Invest 116:1802–1812PubMedCrossRef Prentki M, Nolan CJ (2006) Islet beta cell failure in type 2 diabetes. J Clin Invest 116:1802–1812PubMedCrossRef
3.
Zurück zum Zitat McCarthy MI, Zeggini E (2009) Genome-wide association studies in type 2 diabetes. Curr Diab Rep 9:164–171PubMedCrossRef McCarthy MI, Zeggini E (2009) Genome-wide association studies in type 2 diabetes. Curr Diab Rep 9:164–171PubMedCrossRef
4.
Zurück zum Zitat Palmer CN (2009) Novel insights into the etiology of diabetes from genome-wide association studies. Diabetes 58:2444–2447PubMedCrossRef Palmer CN (2009) Novel insights into the etiology of diabetes from genome-wide association studies. Diabetes 58:2444–2447PubMedCrossRef
5.
Zurück zum Zitat Sladek R, Rocheleau G, Rung J et al (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445:881–885PubMedCrossRef Sladek R, Rocheleau G, Rung J et al (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445:881–885PubMedCrossRef
6.
Zurück zum Zitat Frayling TM (2007) Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev 8:657–662 Frayling TM (2007) Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev 8:657–662
8.
Zurück zum Zitat Lango H, Palmer CN, Morris AD et al (2008) Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk. Diabetes 57:3129–3135PubMedCrossRef Lango H, Palmer CN, Morris AD et al (2008) Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk. Diabetes 57:3129–3135PubMedCrossRef
9.
Zurück zum Zitat Ji J, Wang XW (2009) New kids on the block: diagnostic and prognostic microRNAs in hepatocellular carcinoma. Cancer Biol Ther 8:1686–1693PubMed Ji J, Wang XW (2009) New kids on the block: diagnostic and prognostic microRNAs in hepatocellular carcinoma. Cancer Biol Ther 8:1686–1693PubMed
10.
Zurück zum Zitat Chen X, Ba Y, Ma L et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006PubMedCrossRef Chen X, Ba Y, Ma L et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006PubMedCrossRef
11.
Zurück zum Zitat Gilad S, Meiri E, Yogev Y et al (2008) Serum microRNAs are promising novel biomarkers. PloS One 3:e3148PubMedCrossRef Gilad S, Meiri E, Yogev Y et al (2008) Serum microRNAs are promising novel biomarkers. PloS One 3:e3148PubMedCrossRef
12.
Zurück zum Zitat Mitchell PS, Parkin RK, Kroh EM et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 105:10513–10518PubMedCrossRef Mitchell PS, Parkin RK, Kroh EM et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 105:10513–10518PubMedCrossRef
13.
Zurück zum Zitat Huang Z, Huang D, Ni S et al (2009) Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer Huang Z, Huang D, Ni S et al (2009) Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer
14.
Zurück zum Zitat Jackson DB (2009) Serum-based microRNAs: are we blinded by potential? Proc Natl Acad Sci USA 106:E5PubMedCrossRef Jackson DB (2009) Serum-based microRNAs: are we blinded by potential? Proc Natl Acad Sci USA 106:E5PubMedCrossRef
15.
Zurück zum Zitat Tang X, Tang G, Ozcan S (2008) Role of microRNAs in diabetes. Biochim Biophys Acta 1779:697–701PubMed Tang X, Tang G, Ozcan S (2008) Role of microRNAs in diabetes. Biochim Biophys Acta 1779:697–701PubMed
16.
Zurück zum Zitat Hennessy E, O’Driscoll L (2008) Molecular medicine of microRNAs: structure, function and implications for diabetes. Exp Rev Mol Med 10:e24CrossRef Hennessy E, O’Driscoll L (2008) Molecular medicine of microRNAs: structure, function and implications for diabetes. Exp Rev Mol Med 10:e24CrossRef
17.
Zurück zum Zitat Pandey AK, Agarwal P, Kaur K et al (2009) MicroRNAs in diabetes: tiny players in big disease. Cell Physiol Biochem 23:221–232PubMedCrossRef Pandey AK, Agarwal P, Kaur K et al (2009) MicroRNAs in diabetes: tiny players in big disease. Cell Physiol Biochem 23:221–232PubMedCrossRef
18.
Zurück zum Zitat Tang X, Muniappan L, Tang G et al (2009) Identification of glucose-regulated miRNAs from pancreatic beta cells reveals a role for miR-30d in insulin transcription. RNA 15:287–293PubMedCrossRef Tang X, Muniappan L, Tang G et al (2009) Identification of glucose-regulated miRNAs from pancreatic beta cells reveals a role for miR-30d in insulin transcription. RNA 15:287–293PubMedCrossRef
19.
Zurück zum Zitat Baroukh N, Ravier MA, Loder MK et al (2007) MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic beta-cell lines. J Biol Chem 282:19575–19588PubMedCrossRef Baroukh N, Ravier MA, Loder MK et al (2007) MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic beta-cell lines. J Biol Chem 282:19575–19588PubMedCrossRef
20.
Zurück zum Zitat Plaisance V, Abderrahmani A, Perret-Menoud V et al (2006) MicroRNA-9 controls the expression of Granuphilin/Slp4 and the secretory response of insulin-producing cells. J Biol Chem 281:26932–26942PubMedCrossRef Plaisance V, Abderrahmani A, Perret-Menoud V et al (2006) MicroRNA-9 controls the expression of Granuphilin/Slp4 and the secretory response of insulin-producing cells. J Biol Chem 281:26932–26942PubMedCrossRef
21.
Zurück zum Zitat Poy MN, Eliasson L, Krutzfeldt J et al (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432:226–230PubMedCrossRef Poy MN, Eliasson L, Krutzfeldt J et al (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432:226–230PubMedCrossRef
22.
Zurück zum Zitat He A, Zhu L, Gupta N et al (2007) Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3–L1 adipocytes. Mol Endocrinol 21:2785–2794PubMedCrossRef He A, Zhu L, Gupta N et al (2007) Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3–L1 adipocytes. Mol Endocrinol 21:2785–2794PubMedCrossRef
23.
Zurück zum Zitat Lovis P, Roggli E, Laybutt DR et al (2008) Alterations in microRNA expression contribute to fatty acid-induced pancreatic beta-cell dysfunction. Diabetes 57:2728–2736PubMedCrossRef Lovis P, Roggli E, Laybutt DR et al (2008) Alterations in microRNA expression contribute to fatty acid-induced pancreatic beta-cell dysfunction. Diabetes 57:2728–2736PubMedCrossRef
24.
Zurück zum Zitat (2009) Diagnosis and classification of diabetes mellitus. Diabetes Care 32(Suppl 1):S62–S67 (2009) Diagnosis and classification of diabetes mellitus. Diabetes Care 32(Suppl 1):S62–S67
25.
Zurück zum Zitat Ji J, Zhao L, Budhu A et al (2010) Let-7 g targets collagen type I alpha2 and inhibits cell migration in hepatocellular carcinoma. J Hepatol 52:690–697 Ji J, Zhao L, Budhu A et al (2010) Let-7 g targets collagen type I alpha2 and inhibits cell migration in hepatocellular carcinoma. J Hepatol 52:690–697
26.
Zurück zum Zitat Wong L, Lee K, Russell I et al (2007) Endogenous controls for real-time quantitation of miRNA using TaqMan MicroRNA assays. Macmillan Publishers Limited (all rights reserved), New York Wong L, Lee K, Russell I et al (2007) Endogenous controls for real-time quantitation of miRNA using TaqMan MicroRNA assays. Macmillan Publishers Limited (all rights reserved), New York
27.
Zurück zum Zitat Roggli E, Britan A, Gattesco S et al (2010) Involvement of microRNAs in the cytotoxic effects exerted by proinflammatory cytokines on pancreatic beta-cells. Diabetes 59:978–986 Roggli E, Britan A, Gattesco S et al (2010) Involvement of microRNAs in the cytotoxic effects exerted by proinflammatory cytokines on pancreatic beta-cells. Diabetes 59:978–986
28.
Zurück zum Zitat Feng B, Chen S, George B et al (2010) miR133a regulates cardiomyocyte hypertrophy in diabetes. Diabetes Metab Res Rev 26:40–49 Feng B, Chen S, George B et al (2010) miR133a regulates cardiomyocyte hypertrophy in diabetes. Diabetes Metab Res Rev 26:40–49
29.
Zurück zum Zitat Poy MN, Hausser J, Trajkovski M et al (2009) miR-375 maintains normal pancreatic alpha- and beta-cell mass. Proc Natl Acad Sci USA 106:5813–5818PubMedCrossRef Poy MN, Hausser J, Trajkovski M et al (2009) miR-375 maintains normal pancreatic alpha- and beta-cell mass. Proc Natl Acad Sci USA 106:5813–5818PubMedCrossRef
30.
Zurück zum Zitat Quinn GP, Keough MJ (2002) Experimental design and data analysis for biologists. Cambridge University Press, Cambridge Quinn GP, Keough MJ (2002) Experimental design and data analysis for biologists. Cambridge University Press, Cambridge
31.
Zurück zum Zitat Berezikov E, Guryev V, van de Belt J et al (2005) Phylogenetic shadowing and computational identification of human microRNA genes. Cell 120:21–24PubMedCrossRef Berezikov E, Guryev V, van de Belt J et al (2005) Phylogenetic shadowing and computational identification of human microRNA genes. Cell 120:21–24PubMedCrossRef
32.
Zurück zum Zitat Bentwich I, Avniel A, Karov Y et al (2005) Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37:766–770PubMedCrossRef Bentwich I, Avniel A, Karov Y et al (2005) Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37:766–770PubMedCrossRef
33.
Zurück zum Zitat Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20PubMedCrossRef Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20PubMedCrossRef
34.
Zurück zum Zitat Wu Y, Li H, Loos RJ et al (2008) Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Diabetes 57:2834–2842PubMedCrossRef Wu Y, Li H, Loos RJ et al (2008) Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Diabetes 57:2834–2842PubMedCrossRef
35.
Zurück zum Zitat Ruchat S-M, Elks C, Loos R et al (2009) Association between insulin secretion, insulin sensitivity and type 2 diabetes susceptibility variants identified in genome-wide association studies. Acta Diabetol 46:217–226PubMedCrossRef Ruchat S-M, Elks C, Loos R et al (2009) Association between insulin secretion, insulin sensitivity and type 2 diabetes susceptibility variants identified in genome-wide association studies. Acta Diabetol 46:217–226PubMedCrossRef
36.
Zurück zum Zitat Zhao J, Bradfield JP, Zhang H et al (2010) Examination of all type 2 diabetes GWAS loci reveals HHEX-IDE as a locus influencing pediatric BMI. Diabetes 59:751–755 Zhao J, Bradfield JP, Zhang H et al (2010) Examination of all type 2 diabetes GWAS loci reveals HHEX-IDE as a locus influencing pediatric BMI. Diabetes 59:751–755
37.
Zurück zum Zitat Lantz KA, Vatamaniuk MZ, Brestelli JE et al (2004) Foxa2 regulates multiple pathways of insulin secretion. J Clin Invest 114:512–520PubMed Lantz KA, Vatamaniuk MZ, Brestelli JE et al (2004) Foxa2 regulates multiple pathways of insulin secretion. J Clin Invest 114:512–520PubMed
38.
Zurück zum Zitat Meissner T, Beinbrech B, Mayatepek E (1999) Congenital hyperinsulinism: molecular basis of a heterogeneous disease. Hum Mutat 13:351–361PubMedCrossRef Meissner T, Beinbrech B, Mayatepek E (1999) Congenital hyperinsulinism: molecular basis of a heterogeneous disease. Hum Mutat 13:351–361PubMedCrossRef
39.
Zurück zum Zitat Dinneen SF, Maldonado D 3rd, Leibson CL et al (1998) Effects of changing diagnostic criteria on the risk of developing diabetes. Diabetes Care 21:1408–1413PubMedCrossRef Dinneen SF, Maldonado D 3rd, Leibson CL et al (1998) Effects of changing diagnostic criteria on the risk of developing diabetes. Diabetes Care 21:1408–1413PubMedCrossRef
40.
Zurück zum Zitat Meigs JB, Muller DC, Nathan DM et al (2003) The natural history of progression from normal glucose tolerance to type 2 diabetes in the Baltimore longitudinal study of aging. Diabetes 52:1475–1484PubMedCrossRef Meigs JB, Muller DC, Nathan DM et al (2003) The natural history of progression from normal glucose tolerance to type 2 diabetes in the Baltimore longitudinal study of aging. Diabetes 52:1475–1484PubMedCrossRef
41.
Zurück zum Zitat Tirosh A, Shai I, Tekes-Manova D et al (2005) Normal fasting plasma glucose levels and type 2 diabetes in young men. N Engl J Med 353:1454–1462PubMedCrossRef Tirosh A, Shai I, Tekes-Manova D et al (2005) Normal fasting plasma glucose levels and type 2 diabetes in young men. N Engl J Med 353:1454–1462PubMedCrossRef
42.
Zurück zum Zitat Tuomilehto J, Lindstrom J, Eriksson JG et al (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350PubMedCrossRef Tuomilehto J, Lindstrom J, Eriksson JG et al (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350PubMedCrossRef
43.
Zurück zum Zitat Delahanty LM, Nathan DM (2008) Implications of the diabetes prevention programme and Look AHEAD clinical trials for lifestyle interventions. J Am Diet Assoc 108:S66–S72PubMedCrossRef Delahanty LM, Nathan DM (2008) Implications of the diabetes prevention programme and Look AHEAD clinical trials for lifestyle interventions. J Am Diet Assoc 108:S66–S72PubMedCrossRef
Metadaten
Titel
Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study
verfasst von
Lei Kong
Junjie Zhu
Wenxia Han
Xiuyun Jiang
Min Xu
Yue Zhao
Qiongzhu Dong
Zengfen Pang
Qingbo Guan
Ling Gao
Jiajun Zhao
Lei Zhao
Publikationsdatum
01.03.2011
Verlag
Springer Milan
Erschienen in
Acta Diabetologica / Ausgabe 1/2011
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-010-0226-0

Weitere Artikel der Ausgabe 1/2011

Acta Diabetologica 1/2011 Zur Ausgabe

Review Article

The IGF system

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.