Increased expression of microRNA-15a and microRNA-15b in skeletal muscle from adult offspring of women with diabetes in pregnancy

Azadeh Houshmand-Oeregaard; Maren Schrölkamp; Louise Kelstrup; Ninna S. Hansen; Line Hjort; Anne Cathrine B. Thuesen; Christa Broholm; Elisabeth R. Mathiesen; Tine D. Clausen; Allan Vaag; Peter Damm

doi:10.1093/hmg/ddy085

Increased expression of microRNA-15a and microRNA-15b in skeletal muscle from adult offspring of women with diabetes in pregnancy

Azadeh Houshmand-Oeregaard^*, Maren Schrölkamp, Louise Kelstrup, Ninna S. Hansen, Line Hjort, Anne Cathrine B. Thuesen, Christa Broholm, Elisabeth R. Mathiesen, Tine D. Clausen, Allan Vaag, Peter Damm

^*Corresponding author for this work

Department of Clinical Medicine

21 Citations (Scopus)

Abstract

Offspring of women with diabetes in pregnancy exhibit skeletalmuscle insulin resistance and are at increased risk of developing type 2 diabetes, potentiallymediated by epigeneticmechanisms or changes in the expression of small non-coding microRNAs. Members of the miR-15 family can alter the expression or function of important proteins in the insulin signalling pathway, affecting insulin sensitivity and secretion.We hypothesized that exposure tomaternal diabetesmay cause altered expression of thesemicroRNAs in offspring skeletalmuscle, representing a potential underlyingmechanismby which exposure to maternal diabetes leads to increased risk of cardiometabolic disease in offspring.WemeasuredmicroRNA expression in skeletal muscle biopsies of 26- to 35-year-old offspring of women with either gestational diabetes (O-GDM, n=82) or type 1 diabetes (OT1DM, n=67) in pregnancy, compared with a control group of offspring fromthe background population (O-BP, n=57) froman observational follow-up study. Expression of bothmiR-15a andmiR-15b was increased in skeletalmuscle obtained fromO-GDM (both P < 0.001) and O-T1DM (P=0.024, P=0.005, respectively) compared with O-BP.Maternal 2 h post OGTT glucose levels were positively associated withmiR-15a expression (P=0.041) in O-GDM after adjustment for confounders andmediators. In all groups collectively,miRNA expression was significantly positively associated with fasting plasma glucose, 2 h plasma glucose and HbA1c.We conclude that fetal exposure tomaternal diabetes is associated with increased skeletalmuscle expression of miR-15a andmiR-15b and that thismay contribute to development of metabolic disease in these subjects.

Original language	English
Journal	Human Molecular Genetics
Volume	27
Issue number	10
Pages (from-to)	1763-1771
Number of pages	9
ISSN	0964-6906
DOIs	https://doi.org/10.1093/hmg/ddy085
Publication status	Published - 2018

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https://watermark.silverchair.com/ddy085.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAp8wggKbBgkqhkiG9w0BBwagggKMMIICiAIBADCCAoEGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMguM227GoQV0S-aVpAgEQgIICUjAl07U2yL3Q8hXf17elqxp073gH1S7aEoFi61jqZp0nMWVv07NeJoc2aIo3djpvMuZbiR_F72mFcwr3Y2wcDslt_oaz8YZKG0mwqNsWLlLf5BuMfF5JGgQtah2rBG4wl3FGVhb0B45eNlMzMc5Wopi2jnS88-Pr4PStgGYZuyRE3bhUqGAc0B4f0HRf5gMRymD7YxXh-IiVJbDPDQSx92UfFUOyghTBvPf71qb4ExXx7c3bcuZPf-CYjcQuCCBlOxPb0V-EBh_iwauqVp6oiIrE_1-jI5aTP6rotU4bsvu9mzWDpGKYCo1zTstrUOdqQpLTMXjwal9YogMIQDUFf-9ngtE4bFqWbsTA050xpuVZIon_RDjVzP5YFxr4Hcf0-sUfPpfyGW1AQ9RkQPKR5RTyUDk6E-rPp9F3JAQQx5bHpFlrr0tC1lcjdsYBJAcdwK8bnOMuBvobSdM5GnhEgDikkcm9_i6vHZYN9v9cQ1GRbXJzbkEEPo0GDEkKKHyHAUixwlORVcdU7FzwG4d3VNAa091iDfijd7X8fRg-ecFhvD5YvDFMtqItDCwGCr3xY8jJO8ApsPbojZAqQo_TcsHt6yiBpUVgKFmST5y2A2tHCAuMHL_AexrPjEPFgJFgBIenE43Ly0JBbuX4VrVOkaRbKqdC8CUUdKbLCt6H4n6eSUzMwz6uKwo8iBbmmJkWjwwN6e_boxIelUel0Qzyg1otNsAkULeInJDul3vV-opDqoA_FoRG1cr0V4P21LRlY1CeAseOzCJg8DFbrd0NeEKcbA

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Houshmand-Oeregaard, A., Schrölkamp, M., Kelstrup, L., Hansen, N. S., Hjort, L., Thuesen, A. C. B., Broholm, C., Mathiesen, E. R., Clausen, T. D., Vaag, A., & Damm, P. (2018). Increased expression of microRNA-15a and microRNA-15b in skeletal muscle from adult offspring of women with diabetes in pregnancy. Human Molecular Genetics, 27(10), 1763-1771. https://doi.org/10.1093/hmg/ddy085

Houshmand-Oeregaard, A, Schrölkamp, M, Kelstrup, L, Hansen, NS, Hjort, L, Thuesen, ACB, Broholm, C, Mathiesen, ER, Clausen, TD, Vaag, A & Damm, P 2018, 'Increased expression of microRNA-15a and microRNA-15b in skeletal muscle from adult offspring of women with diabetes in pregnancy', Human Molecular Genetics, vol. 27, no. 10, pp. 1763-1771. https://doi.org/10.1093/hmg/ddy085

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title = "Increased expression of microRNA-15a and microRNA-15b in skeletal muscle from adult offspring of women with diabetes in pregnancy",

abstract = "Offspring of women with diabetes in pregnancy exhibit skeletalmuscle insulin resistance and are at increased risk of developing type 2 diabetes, potentiallymediated by epigeneticmechanisms or changes in the expression of small non-coding microRNAs. Members of the miR-15 family can alter the expression or function of important proteins in the insulin signalling pathway, affecting insulin sensitivity and secretion.We hypothesized that exposure tomaternal diabetesmay cause altered expression of thesemicroRNAs in offspring skeletalmuscle, representing a potential underlyingmechanismby which exposure to maternal diabetes leads to increased risk of cardiometabolic disease in offspring.WemeasuredmicroRNA expression in skeletal muscle biopsies of 26- to 35-year-old offspring of women with either gestational diabetes (O-GDM, n=82) or type 1 diabetes (OT1DM, n=67) in pregnancy, compared with a control group of offspring fromthe background population (O-BP, n=57) froman observational follow-up study. Expression of bothmiR-15a andmiR-15b was increased in skeletalmuscle obtained fromO-GDM (both P < 0.001) and O-T1DM (P=0.024, P=0.005, respectively) compared with O-BP.Maternal 2 h post OGTT glucose levels were positively associated withmiR-15a expression (P=0.041) in O-GDM after adjustment for confounders andmediators. In all groups collectively,miRNA expression was significantly positively associated with fasting plasma glucose, 2 h plasma glucose and HbA1c.We conclude that fetal exposure tomaternal diabetes is associated with increased skeletalmuscle expression of miR-15a andmiR-15b and that thismay contribute to development of metabolic disease in these subjects.",

author = "Azadeh Houshmand-Oeregaard and Maren Schr{\"o}lkamp and Louise Kelstrup and Hansen, {Ninna S.} and Line Hjort and Thuesen, {Anne Cathrine B.} and Christa Broholm and Mathiesen, {Elisabeth R.} and Clausen, {Tine D.} and Allan Vaag and Peter Damm",

year = "2018",

doi = "10.1093/hmg/ddy085",

language = "English",

volume = "27",

pages = "1763--1771",

journal = "Human Molecular Genetics",

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publisher = "Oxford University Press",

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TY - JOUR

T1 - Increased expression of microRNA-15a and microRNA-15b in skeletal muscle from adult offspring of women with diabetes in pregnancy

AU - Houshmand-Oeregaard, Azadeh

AU - Schrölkamp, Maren

AU - Kelstrup, Louise

AU - Hansen, Ninna S.

AU - Hjort, Line

AU - Thuesen, Anne Cathrine B.

AU - Broholm, Christa

AU - Mathiesen, Elisabeth R.

AU - Clausen, Tine D.

AU - Vaag, Allan

AU - Damm, Peter

PY - 2018

Y1 - 2018

N2 - Offspring of women with diabetes in pregnancy exhibit skeletalmuscle insulin resistance and are at increased risk of developing type 2 diabetes, potentiallymediated by epigeneticmechanisms or changes in the expression of small non-coding microRNAs. Members of the miR-15 family can alter the expression or function of important proteins in the insulin signalling pathway, affecting insulin sensitivity and secretion.We hypothesized that exposure tomaternal diabetesmay cause altered expression of thesemicroRNAs in offspring skeletalmuscle, representing a potential underlyingmechanismby which exposure to maternal diabetes leads to increased risk of cardiometabolic disease in offspring.WemeasuredmicroRNA expression in skeletal muscle biopsies of 26- to 35-year-old offspring of women with either gestational diabetes (O-GDM, n=82) or type 1 diabetes (OT1DM, n=67) in pregnancy, compared with a control group of offspring fromthe background population (O-BP, n=57) froman observational follow-up study. Expression of bothmiR-15a andmiR-15b was increased in skeletalmuscle obtained fromO-GDM (both P < 0.001) and O-T1DM (P=0.024, P=0.005, respectively) compared with O-BP.Maternal 2 h post OGTT glucose levels were positively associated withmiR-15a expression (P=0.041) in O-GDM after adjustment for confounders andmediators. In all groups collectively,miRNA expression was significantly positively associated with fasting plasma glucose, 2 h plasma glucose and HbA1c.We conclude that fetal exposure tomaternal diabetes is associated with increased skeletalmuscle expression of miR-15a andmiR-15b and that thismay contribute to development of metabolic disease in these subjects.

AB - Offspring of women with diabetes in pregnancy exhibit skeletalmuscle insulin resistance and are at increased risk of developing type 2 diabetes, potentiallymediated by epigeneticmechanisms or changes in the expression of small non-coding microRNAs. Members of the miR-15 family can alter the expression or function of important proteins in the insulin signalling pathway, affecting insulin sensitivity and secretion.We hypothesized that exposure tomaternal diabetesmay cause altered expression of thesemicroRNAs in offspring skeletalmuscle, representing a potential underlyingmechanismby which exposure to maternal diabetes leads to increased risk of cardiometabolic disease in offspring.WemeasuredmicroRNA expression in skeletal muscle biopsies of 26- to 35-year-old offspring of women with either gestational diabetes (O-GDM, n=82) or type 1 diabetes (OT1DM, n=67) in pregnancy, compared with a control group of offspring fromthe background population (O-BP, n=57) froman observational follow-up study. Expression of bothmiR-15a andmiR-15b was increased in skeletalmuscle obtained fromO-GDM (both P < 0.001) and O-T1DM (P=0.024, P=0.005, respectively) compared with O-BP.Maternal 2 h post OGTT glucose levels were positively associated withmiR-15a expression (P=0.041) in O-GDM after adjustment for confounders andmediators. In all groups collectively,miRNA expression was significantly positively associated with fasting plasma glucose, 2 h plasma glucose and HbA1c.We conclude that fetal exposure tomaternal diabetes is associated with increased skeletalmuscle expression of miR-15a andmiR-15b and that thismay contribute to development of metabolic disease in these subjects.

U2 - 10.1093/hmg/ddy085

DO - 10.1093/hmg/ddy085

M3 - Journal article

C2 - 29528396

AN - SCOPUS:85047008355

SN - 0964-6906

VL - 27

SP - 1763

EP - 1771

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 10

ER -

Increased expression of microRNA-15a and microRNA-15b in skeletal muscle from adult offspring of women with diabetes in pregnancy

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