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Adipose tissue INSR splicing in humans associates with fasting insulin level and is regulated by weight loss

Aims/hypothesis The insulin receptor (INSR) has two protein isoforms based on alternative splicing of exon 11. INSR-A promotes cell growth whereas INSR-B predominantly regulates glucose homeostasis. In this study we investigated whether weight loss regulates INSR alternative splicing and the express... Full description

Journal Title: Diabetologia 2013-11-07, Vol.57 (2), p.347-351
Main Author: Kaminska, Dorota
Other Authors: Hämäläinen, Maija , Cederberg, Henna , Käkelä, Pirjo , Venesmaa, Sari , Miettinen, Pekka , Ilves, Imre , Herzig, Karl-Heinz , Kolehmainen, Marjukka , Karhunen, Leila , Kuusisto, Johanna , Gylling, Helena , Laakso, Markku , Pihlajamäki, Jussi
Format: Electronic Article Electronic Article
Language: English
Subjects:
RNA
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
ID: ISSN: 0012-186X
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title: Adipose tissue INSR splicing in humans associates with fasting insulin level and is regulated by weight loss
format: Article
creator:
  • Kaminska, Dorota
  • Hämäläinen, Maija
  • Cederberg, Henna
  • Käkelä, Pirjo
  • Venesmaa, Sari
  • Miettinen, Pekka
  • Ilves, Imre
  • Herzig, Karl-Heinz
  • Kolehmainen, Marjukka
  • Karhunen, Leila
  • Kuusisto, Johanna
  • Gylling, Helena
  • Laakso, Markku
  • Pihlajamäki, Jussi
subjects:
  • Adipose Tissue - metabolism
  • Adipose tissues
  • Alternative Splicing
  • Antigens, CD - genetics
  • Antigens, CD - metabolism
  • Bariatric Surgery
  • Biological and medical sciences
  • Blood Glucose - metabolism
  • Body Mass Index
  • Caloric Restriction
  • Dextrose
  • Diabetes. Impaired glucose tolerance
  • Diet, Reducing
  • Electrophoresis, Capillary
  • Endocrine pancreas. Apud cells (diseases)
  • Endocrinopathies
  • Etiopathogenesis. Screening. Investigations. Target tissue resistance
  • Fasting
  • Female
  • Glucose
  • Glucose metabolism
  • Human Physiology
  • Humans
  • Insulin
  • Insulin - blood
  • Insulin Resistance - genetics
  • Internal Medicine
  • Male
  • Medical sciences
  • Medicine
  • Medicine & Public Health
  • Metabolic Diseases
  • Middle Aged
  • Obesity
  • Receptor, Insulin - genetics
  • Receptor, Insulin - metabolism
  • RNA
  • Short Communication
  • Surgery
  • Weight Loss
ispartof: Diabetologia, 2013-11-07, Vol.57 (2), p.347-351
description: Aims/hypothesis The insulin receptor (INSR) has two protein isoforms based on alternative splicing of exon 11. INSR-A promotes cell growth whereas INSR-B predominantly regulates glucose homeostasis. In this study we investigated whether weight loss regulates INSR alternative splicing and the expression of splicing factors in adipose tissue. Methods To determine the relative ratio of the INSR splice variants, we implemented the PCR-capillary electrophoresis method with adipose tissue samples from two weight-loss-intervention studies, the Kuopio Obesity Surgery study (KOBS, n  = 108) and a very low calorie diet (VLCD) intervention ( n  = 32), and from the population-based Metabolic Syndrome in Men study (METSIM, n  = 49). Results Expression of INSR-B mRNA variant increased in response to weight loss induced by both bariatric surgery ( p  = 1 × 10 −5 ) and the VLCD ( p  = 1 × 10 −4 ). The adipose tissue expression of INSR-B correlated negatively with fasting insulin levels in the pooled data of the three studies ( p  = 3 × 10 −22 ). Finally, expression of several splicing factors correlated negatively with the expression of the INSR-B variant. The strongest correlation was with HNRNPA1 ( p  = 1 × 10 −5 ), a known regulator of INSR exon 11 splicing. Conclusions/interpretation INSR splicing is regulated by weight loss and associates with insulin levels. The effect of weight loss on INSR splicing could be mediated by changes in the expression of splicing factors.
language: eng
source:
identifier: ISSN: 0012-186X
fulltext: no_fulltext
issn:
  • 0012-186X
  • 1432-0428
url: Link


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titleAdipose tissue INSR splicing in humans associates with fasting insulin level and is regulated by weight loss
creatorKaminska, Dorota ; Hämäläinen, Maija ; Cederberg, Henna ; Käkelä, Pirjo ; Venesmaa, Sari ; Miettinen, Pekka ; Ilves, Imre ; Herzig, Karl-Heinz ; Kolehmainen, Marjukka ; Karhunen, Leila ; Kuusisto, Johanna ; Gylling, Helena ; Laakso, Markku ; Pihlajamäki, Jussi
creatorcontribKaminska, Dorota ; Hämäläinen, Maija ; Cederberg, Henna ; Käkelä, Pirjo ; Venesmaa, Sari ; Miettinen, Pekka ; Ilves, Imre ; Herzig, Karl-Heinz ; Kolehmainen, Marjukka ; Karhunen, Leila ; Kuusisto, Johanna ; Gylling, Helena ; Laakso, Markku ; Pihlajamäki, Jussi
descriptionAims/hypothesis The insulin receptor (INSR) has two protein isoforms based on alternative splicing of exon 11. INSR-A promotes cell growth whereas INSR-B predominantly regulates glucose homeostasis. In this study we investigated whether weight loss regulates INSR alternative splicing and the expression of splicing factors in adipose tissue. Methods To determine the relative ratio of the INSR splice variants, we implemented the PCR-capillary electrophoresis method with adipose tissue samples from two weight-loss-intervention studies, the Kuopio Obesity Surgery study (KOBS, n  = 108) and a very low calorie diet (VLCD) intervention ( n  = 32), and from the population-based Metabolic Syndrome in Men study (METSIM, n  = 49). Results Expression of INSR-B mRNA variant increased in response to weight loss induced by both bariatric surgery ( p  = 1 × 10 −5 ) and the VLCD ( p  = 1 × 10 −4 ). The adipose tissue expression of INSR-B correlated negatively with fasting insulin levels in the pooled data of the three studies ( p  = 3 × 10 −22 ). Finally, expression of several splicing factors correlated negatively with the expression of the INSR-B variant. The strongest correlation was with HNRNPA1 ( p  = 1 × 10 −5 ), a known regulator of INSR exon 11 splicing. Conclusions/interpretation INSR splicing is regulated by weight loss and associates with insulin levels. The effect of weight loss on INSR splicing could be mediated by changes in the expression of splicing factors.
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languageeng
publisherBerlin/Heidelberg: Springer Berlin Heidelberg
subjectAdipose Tissue - metabolism ; Adipose tissues ; Alternative Splicing ; Antigens, CD - genetics ; Antigens, CD - metabolism ; Bariatric Surgery ; Biological and medical sciences ; Blood Glucose - metabolism ; Body Mass Index ; Caloric Restriction ; Dextrose ; Diabetes. Impaired glucose tolerance ; Diet, Reducing ; Electrophoresis, Capillary ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Fasting ; Female ; Glucose ; Glucose metabolism ; Human Physiology ; Humans ; Insulin ; Insulin - blood ; Insulin Resistance - genetics ; Internal Medicine ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Middle Aged ; Obesity ; Receptor, Insulin - genetics ; Receptor, Insulin - metabolism ; RNA ; Short Communication ; Surgery ; Weight Loss
ispartofDiabetologia, 2013-11-07, Vol.57 (2), p.347-351
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1Hämäläinen, Maija
2Cederberg, Henna
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5Miettinen, Pekka
6Ilves, Imre
7Herzig, Karl-Heinz
8Kolehmainen, Marjukka
9Karhunen, Leila
10Kuusisto, Johanna
11Gylling, Helena
12Laakso, Markku
13Pihlajamäki, Jussi
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0Adipose tissue INSR splicing in humans associates with fasting insulin level and is regulated by weight loss
1Diabetologia
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descriptionAims/hypothesis The insulin receptor (INSR) has two protein isoforms based on alternative splicing of exon 11. INSR-A promotes cell growth whereas INSR-B predominantly regulates glucose homeostasis. In this study we investigated whether weight loss regulates INSR alternative splicing and the expression of splicing factors in adipose tissue. Methods To determine the relative ratio of the INSR splice variants, we implemented the PCR-capillary electrophoresis method with adipose tissue samples from two weight-loss-intervention studies, the Kuopio Obesity Surgery study (KOBS, n  = 108) and a very low calorie diet (VLCD) intervention ( n  = 32), and from the population-based Metabolic Syndrome in Men study (METSIM, n  = 49). Results Expression of INSR-B mRNA variant increased in response to weight loss induced by both bariatric surgery ( p  = 1 × 10 −5 ) and the VLCD ( p  = 1 × 10 −4 ). The adipose tissue expression of INSR-B correlated negatively with fasting insulin levels in the pooled data of the three studies ( p  = 3 × 10 −22 ). Finally, expression of several splicing factors correlated negatively with the expression of the INSR-B variant. The strongest correlation was with HNRNPA1 ( p  = 1 × 10 −5 ), a known regulator of INSR exon 11 splicing. Conclusions/interpretation INSR splicing is regulated by weight loss and associates with insulin levels. The effect of weight loss on INSR splicing could be mediated by changes in the expression of splicing factors.
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0Adipose Tissue - metabolism
1Adipose tissues
2Alternative Splicing
3Antigens, CD - genetics
4Antigens, CD - metabolism
5Bariatric Surgery
6Biological and medical sciences
7Blood Glucose - metabolism
8Body Mass Index
9Caloric Restriction
10Dextrose
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12Diet, Reducing
13Electrophoresis, Capillary
14Endocrine pancreas. Apud cells (diseases)
15Endocrinopathies
16Etiopathogenesis. Screening. Investigations. Target tissue resistance
17Fasting
18Female
19Glucose
20Glucose metabolism
21Human Physiology
22Humans
23Insulin
24Insulin - blood
25Insulin Resistance - genetics
26Internal Medicine
27Male
28Medical sciences
29Medicine
30Medicine & Public Health
31Metabolic Diseases
32Middle Aged
33Obesity
34Receptor, Insulin - genetics
35Receptor, Insulin - metabolism
36RNA
37Short Communication
38Surgery
39Weight Loss
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7Herzig, Karl-Heinz
8Kolehmainen, Marjukka
9Karhunen, Leila
10Kuusisto, Johanna
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titleAdipose tissue INSR splicing in humans associates with fasting insulin level and is regulated by weight loss
authorKaminska, Dorota ; Hämäläinen, Maija ; Cederberg, Henna ; Käkelä, Pirjo ; Venesmaa, Sari ; Miettinen, Pekka ; Ilves, Imre ; Herzig, Karl-Heinz ; Kolehmainen, Marjukka ; Karhunen, Leila ; Kuusisto, Johanna ; Gylling, Helena ; Laakso, Markku ; Pihlajamäki, Jussi
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1Adipose tissues
2Alternative Splicing
3Antigens, CD - genetics
4Antigens, CD - metabolism
5Bariatric Surgery
6Biological and medical sciences
7Blood Glucose - metabolism
8Body Mass Index
9Caloric Restriction
10Dextrose
11Diabetes. Impaired glucose tolerance
12Diet, Reducing
13Electrophoresis, Capillary
14Endocrine pancreas. Apud cells (diseases)
15Endocrinopathies
16Etiopathogenesis. Screening. Investigations. Target tissue resistance
17Fasting
18Female
19Glucose
20Glucose metabolism
21Human Physiology
22Humans
23Insulin
24Insulin - blood
25Insulin Resistance - genetics
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28Medical sciences
29Medicine
30Medicine & Public Health
31Metabolic Diseases
32Middle Aged
33Obesity
34Receptor, Insulin - genetics
35Receptor, Insulin - metabolism
36RNA
37Short Communication
38Surgery
39Weight Loss
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2Cederberg, Henna
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4Venesmaa, Sari
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7Herzig, Karl-Heinz
8Kolehmainen, Marjukka
9Karhunen, Leila
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7Herzig, Karl-Heinz
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atitleAdipose tissue INSR splicing in humans associates with fasting insulin level and is regulated by weight loss
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abstractAims/hypothesis The insulin receptor (INSR) has two protein isoforms based on alternative splicing of exon 11. INSR-A promotes cell growth whereas INSR-B predominantly regulates glucose homeostasis. In this study we investigated whether weight loss regulates INSR alternative splicing and the expression of splicing factors in adipose tissue. Methods To determine the relative ratio of the INSR splice variants, we implemented the PCR-capillary electrophoresis method with adipose tissue samples from two weight-loss-intervention studies, the Kuopio Obesity Surgery study (KOBS, n  = 108) and a very low calorie diet (VLCD) intervention ( n  = 32), and from the population-based Metabolic Syndrome in Men study (METSIM, n  = 49). Results Expression of INSR-B mRNA variant increased in response to weight loss induced by both bariatric surgery ( p  = 1 × 10 −5 ) and the VLCD ( p  = 1 × 10 −4 ). The adipose tissue expression of INSR-B correlated negatively with fasting insulin levels in the pooled data of the three studies ( p  = 3 × 10 −22 ). Finally, expression of several splicing factors correlated negatively with the expression of the INSR-B variant. The strongest correlation was with HNRNPA1 ( p  = 1 × 10 −5 ), a known regulator of INSR exon 11 splicing. Conclusions/interpretation INSR splicing is regulated by weight loss and associates with insulin levels. The effect of weight loss on INSR splicing could be mediated by changes in the expression of splicing factors.
copBerlin/Heidelberg
pubSpringer Berlin Heidelberg
pmid24196191
doi10.1007/s00125-013-3097-4