Effect of a common variant of the PCSK2 gene on reduced insulin secretion.
(2012) In Diabetologia- Abstract
- AIM/HYPOTHESIS:
Individuals at risk of developing type 2 diabetes show a progressive decline in insulin secretion and increased insulin resistance over time. However, inability of the beta cells to compensate for the increased insulin resistance represents a key defect leading to overt type 2 diabetes. The aims of the present study were to replicate the association between genetic variants of the PCSK2 gene and insulin secretion, and to explore the effect on risk of type 2 diabetes.
METHODS: Replication of PCSK2 variants against insulin secretion included 7,682 non-diabetic Scandinavian individuals. Insulin secretion was measured as the corrected insulin response or disposition index, i.e. insulin secretion... (More) - AIM/HYPOTHESIS:
Individuals at risk of developing type 2 diabetes show a progressive decline in insulin secretion and increased insulin resistance over time. However, inability of the beta cells to compensate for the increased insulin resistance represents a key defect leading to overt type 2 diabetes. The aims of the present study were to replicate the association between genetic variants of the PCSK2 gene and insulin secretion, and to explore the effect on risk of type 2 diabetes.
METHODS: Replication of PCSK2 variants against insulin secretion included 7,682 non-diabetic Scandinavian individuals. Insulin secretion was measured as the corrected insulin response or disposition index, i.e. insulin secretion adjusted for the degree of insulin resistance. Risk of type 2 diabetes was studied in 28,287 Scandinavian individuals.
RESULTS: The C-allele of PCSK2 rs2208203 was associated with reduced insulin secretion measured as the corrected insulin response (n = 8,151; β = -0.112, p = 1.3 × 10(-6)) as well as disposition index (n = 8,078, β = -0.128, p = 1.6 × 10(-7)). The variant was also associated with lower fasting glucagon levels (β = -0.084, p = 0.005) in non-diabetic individuals with a fasting plasma glucose of over 5.5 mmol/l. In human pancreatic islets, PCSK2 expression correlated negatively with HbA(1c) (n = 133, r = -0.196, p = 0.038), and showed a tendency to be lower in hyperglycaemic (HbA(1c) ≥6.0% or type 2 diabetes; n = 47, p = 0.13) than normoglycaemic (HbA(1c) >6.0%; n = 66) donors. The presence of the PCSK2 rs2208203 risk allele did not influence gene expression, nor did it show an apparent risk in terms of type 2 diabetes.
CONCLUSIONS/INTERPRETATION:
A variant of the PCSK2 gene was associated with reduced glucose-stimulated insulin secretion, but also with lower glucagon levels, which could potentially counteract the effects of decreased insulin secretion on the risk of type 2 diabetes. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3123654
- author
- Jonsson, Anna LU ; Isomaa, B ; Tuomi, Tiinamaija ; Eriksson, Jonas ; Groop, Leif LU and Lyssenko, Valeriya LU
- organization
- publishing date
- 2012-09-26
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetologia
- publisher
- Springer
- external identifiers
-
- wos:000310381800013
- pmid:23011353
- scopus:84868214928
- pmid:23011353
- ISSN
- 1432-0428
- DOI
- 10.1007/s00125-012-2728-5
- language
- English
- LU publication?
- yes
- id
- eb414a48-c77e-4ebd-8289-0cfe366cd6b4 (old id 3123654)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23011353?dopt=Abstract
- date added to LUP
- 2016-04-04 08:56:35
- date last changed
- 2024-01-12 08:07:56
@article{eb414a48-c77e-4ebd-8289-0cfe366cd6b4,
abstract = {{AIM/HYPOTHESIS: <br/><br>
Individuals at risk of developing type 2 diabetes show a progressive decline in insulin secretion and increased insulin resistance over time. However, inability of the beta cells to compensate for the increased insulin resistance represents a key defect leading to overt type 2 diabetes. The aims of the present study were to replicate the association between genetic variants of the PCSK2 gene and insulin secretion, and to explore the effect on risk of type 2 diabetes. <br/><br>
<br/><br>
METHODS: Replication of PCSK2 variants against insulin secretion included 7,682 non-diabetic Scandinavian individuals. Insulin secretion was measured as the corrected insulin response or disposition index, i.e. insulin secretion adjusted for the degree of insulin resistance. Risk of type 2 diabetes was studied in 28,287 Scandinavian individuals. <br/><br>
<br/><br>
RESULTS: The C-allele of PCSK2 rs2208203 was associated with reduced insulin secretion measured as the corrected insulin response (n = 8,151; β = -0.112, p = 1.3 × 10(-6)) as well as disposition index (n = 8,078, β = -0.128, p = 1.6 × 10(-7)). The variant was also associated with lower fasting glucagon levels (β = -0.084, p = 0.005) in non-diabetic individuals with a fasting plasma glucose of over 5.5 mmol/l. In human pancreatic islets, PCSK2 expression correlated negatively with HbA(1c) (n = 133, r = -0.196, p = 0.038), and showed a tendency to be lower in hyperglycaemic (HbA(1c) ≥6.0% or type 2 diabetes; n = 47, p = 0.13) than normoglycaemic (HbA(1c) >6.0%; n = 66) donors. The presence of the PCSK2 rs2208203 risk allele did not influence gene expression, nor did it show an apparent risk in terms of type 2 diabetes. <br/><br>
<br/><br>
CONCLUSIONS/INTERPRETATION: <br/><br>
A variant of the PCSK2 gene was associated with reduced glucose-stimulated insulin secretion, but also with lower glucagon levels, which could potentially counteract the effects of decreased insulin secretion on the risk of type 2 diabetes.}},
author = {{Jonsson, Anna and Isomaa, B and Tuomi, Tiinamaija and Eriksson, Jonas and Groop, Leif and Lyssenko, Valeriya}},
issn = {{1432-0428}},
language = {{eng}},
month = {{09}},
publisher = {{Springer}},
series = {{Diabetologia}},
title = {{Effect of a common variant of the PCSK2 gene on reduced insulin secretion.}},
url = {{http://dx.doi.org/10.1007/s00125-012-2728-5}},
doi = {{10.1007/s00125-012-2728-5}},
year = {{2012}},
}