Decreased protein levels of key insulin signalling molecules in adipose tissue from young men with a low birthweight: potential link to increased risk of diabetes?

S E Ozanne; C B Jensen; K J Tingey; M S Martin-Gronert; L Grunnet; C Brons; H Storgaard; A A Vaag

doi:10.1007/s00125-006-0466-2

Decreased protein levels of key insulin signalling molecules in adipose tissue from young men with a low birthweight: potential link to increased risk of diabetes?

S E Ozanne, C B Jensen, K J Tingey, M S Martin-Gronert, L Grunnet, C Brons, H Storgaard, A A Vaag

73 Citationer (Scopus)

Abstract

AIMS/HYPOTHESIS: Individuals with low birthweight are at increased risk of type 2 diabetes mellitus. However, the underlying molecular mechanisms are unknown. Previously we have shown that low birthweight is associated with changes in muscle insulin signalling proteins. Here we determined whether low birthweight is associated with changes in insulin signalling proteins in adipose tissue.

METHODS: Men (age 23 years) with either a low (bottom 10th percentile) (n = 17) or a normal (50th-90th percentile) (n = 17) birthweight were recruited from the Danish Medical Birth Registry and subcutaneous adipose biopsies were taken.

RESULTS: Between the two groups there was no difference in protein level of the insulin receptor, protein kinase C zeta, glycogen synthase kinase-3 (GSK3) alpha, GSK3 beta, protein kinase B alpha and beta, peroxisome proliferative activated receptor gamma coactivator 1 or Src-homology-2-containing protein. However, the levels of GLUT4 (also known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) (52 +/- 10.9% reduction, p < 0.01), p85alpha subunit of phosphoinositide 3-kinase (PI3K) (45 +/- 9% reduction, p < 0.01), p110ss subunit of PI3K (48 +/- 17% reduction, p = 0.06) and IRS1 (59 +/- 24% reduction, p < 0.05) were reduced in men of low birthweight.

CONCLUSIONS/INTERPRETATION: These findings show that low birthweight is associated with reduced levels of adipose insulin signalling proteins, thus providing a potential molecular framework to explain why people with low birthweight are at increased risk of developing type 2 diabetes. These differences precede the development of diabetes and thus may help predict disease risk.

Originalsprog	Engelsk
Tidsskrift	Diabetologia
Vol/bind	49
Udgave nummer	12
Sider (fra-til)	2993-9
Antal sider	7
ISSN	0012-186X
DOI	https://doi.org/10.1007/s00125-006-0466-2
Status	Udgivet - dec. 2006
Udgivet eksternt	Ja

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10.1007/s00125-006-0466-2

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@article{6b9e35fd60c4498ca3a4ec98a0d1088c,

title = "Decreased protein levels of key insulin signalling molecules in adipose tissue from young men with a low birthweight: potential link to increased risk of diabetes?",

abstract = "AIMS/HYPOTHESIS: Individuals with low birthweight are at increased risk of type 2 diabetes mellitus. However, the underlying molecular mechanisms are unknown. Previously we have shown that low birthweight is associated with changes in muscle insulin signalling proteins. Here we determined whether low birthweight is associated with changes in insulin signalling proteins in adipose tissue.METHODS: Men (age 23 years) with either a low (bottom 10th percentile) (n = 17) or a normal (50th-90th percentile) (n = 17) birthweight were recruited from the Danish Medical Birth Registry and subcutaneous adipose biopsies were taken.RESULTS: Between the two groups there was no difference in protein level of the insulin receptor, protein kinase C zeta, glycogen synthase kinase-3 (GSK3) alpha, GSK3 beta, protein kinase B alpha and beta, peroxisome proliferative activated receptor gamma coactivator 1 or Src-homology-2-containing protein. However, the levels of GLUT4 (also known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) (52 +/- 10.9% reduction, p < 0.01), p85alpha subunit of phosphoinositide 3-kinase (PI3K) (45 +/- 9% reduction, p < 0.01), p110ss subunit of PI3K (48 +/- 17% reduction, p = 0.06) and IRS1 (59 +/- 24% reduction, p < 0.05) were reduced in men of low birthweight.CONCLUSIONS/INTERPRETATION: These findings show that low birthweight is associated with reduced levels of adipose insulin signalling proteins, thus providing a potential molecular framework to explain why people with low birthweight are at increased risk of developing type 2 diabetes. These differences precede the development of diabetes and thus may help predict disease risk.",

keywords = "Adipose Tissue/metabolism, Adult, Biopsy, Birth Weight, Blood Proteins/metabolism, Diabetes Mellitus, Type 2/epidemiology, Glucose Transporter Type 4/genetics, Glycogen Synthase Kinase 3/genetics, Humans, Infant, Low Birth Weight, Infant, Newborn, Male, Phosphatidylinositol 3-Kinases/genetics, RNA, Messenger/genetics, Risk Assessment",

author = "Ozanne, {S E} and Jensen, {C B} and Tingey, {K J} and Martin-Gronert, {M S} and L Grunnet and C Brons and H Storgaard and Vaag, {A A}",

year = "2006",

month = dec,

doi = "10.1007/s00125-006-0466-2",

language = "English",

volume = "49",

pages = "2993--9",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer",

number = "12",

}

TY - JOUR

T1 - Decreased protein levels of key insulin signalling molecules in adipose tissue from young men with a low birthweight

T2 - potential link to increased risk of diabetes?

AU - Ozanne, S E

AU - Jensen, C B

AU - Tingey, K J

AU - Martin-Gronert, M S

AU - Grunnet, L

AU - Brons, C

AU - Storgaard, H

AU - Vaag, A A

PY - 2006/12

Y1 - 2006/12

N2 - AIMS/HYPOTHESIS: Individuals with low birthweight are at increased risk of type 2 diabetes mellitus. However, the underlying molecular mechanisms are unknown. Previously we have shown that low birthweight is associated with changes in muscle insulin signalling proteins. Here we determined whether low birthweight is associated with changes in insulin signalling proteins in adipose tissue.METHODS: Men (age 23 years) with either a low (bottom 10th percentile) (n = 17) or a normal (50th-90th percentile) (n = 17) birthweight were recruited from the Danish Medical Birth Registry and subcutaneous adipose biopsies were taken.RESULTS: Between the two groups there was no difference in protein level of the insulin receptor, protein kinase C zeta, glycogen synthase kinase-3 (GSK3) alpha, GSK3 beta, protein kinase B alpha and beta, peroxisome proliferative activated receptor gamma coactivator 1 or Src-homology-2-containing protein. However, the levels of GLUT4 (also known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) (52 +/- 10.9% reduction, p < 0.01), p85alpha subunit of phosphoinositide 3-kinase (PI3K) (45 +/- 9% reduction, p < 0.01), p110ss subunit of PI3K (48 +/- 17% reduction, p = 0.06) and IRS1 (59 +/- 24% reduction, p < 0.05) were reduced in men of low birthweight.CONCLUSIONS/INTERPRETATION: These findings show that low birthweight is associated with reduced levels of adipose insulin signalling proteins, thus providing a potential molecular framework to explain why people with low birthweight are at increased risk of developing type 2 diabetes. These differences precede the development of diabetes and thus may help predict disease risk.

AB - AIMS/HYPOTHESIS: Individuals with low birthweight are at increased risk of type 2 diabetes mellitus. However, the underlying molecular mechanisms are unknown. Previously we have shown that low birthweight is associated with changes in muscle insulin signalling proteins. Here we determined whether low birthweight is associated with changes in insulin signalling proteins in adipose tissue.METHODS: Men (age 23 years) with either a low (bottom 10th percentile) (n = 17) or a normal (50th-90th percentile) (n = 17) birthweight were recruited from the Danish Medical Birth Registry and subcutaneous adipose biopsies were taken.RESULTS: Between the two groups there was no difference in protein level of the insulin receptor, protein kinase C zeta, glycogen synthase kinase-3 (GSK3) alpha, GSK3 beta, protein kinase B alpha and beta, peroxisome proliferative activated receptor gamma coactivator 1 or Src-homology-2-containing protein. However, the levels of GLUT4 (also known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) (52 +/- 10.9% reduction, p < 0.01), p85alpha subunit of phosphoinositide 3-kinase (PI3K) (45 +/- 9% reduction, p < 0.01), p110ss subunit of PI3K (48 +/- 17% reduction, p = 0.06) and IRS1 (59 +/- 24% reduction, p < 0.05) were reduced in men of low birthweight.CONCLUSIONS/INTERPRETATION: These findings show that low birthweight is associated with reduced levels of adipose insulin signalling proteins, thus providing a potential molecular framework to explain why people with low birthweight are at increased risk of developing type 2 diabetes. These differences precede the development of diabetes and thus may help predict disease risk.

KW - Adipose Tissue/metabolism

KW - Adult

KW - Biopsy

KW - Birth Weight

KW - Blood Proteins/metabolism

KW - Diabetes Mellitus, Type 2/epidemiology

KW - Glucose Transporter Type 4/genetics

KW - Glycogen Synthase Kinase 3/genetics

KW - Humans

KW - Infant, Low Birth Weight

KW - Infant, Newborn

KW - Male

KW - Phosphatidylinositol 3-Kinases/genetics

KW - RNA, Messenger/genetics

KW - Risk Assessment

U2 - 10.1007/s00125-006-0466-2

DO - 10.1007/s00125-006-0466-2

M3 - Journal article

C2 - 17063325

SN - 0012-186X

VL - 49

SP - 2993

EP - 2999

JO - Diabetologia

JF - Diabetologia

IS - 12

ER -

Decreased protein levels of key insulin signalling molecules in adipose tissue from young men with a low birthweight: potential link to increased risk of diabetes?

Abstract

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