Longer HSD11B2 CA-repeat in impaired glucose tolerance and type 2 diabetes

Tomoatsu Mune, Tetsuya Suwa, Hiroyuki Morita, Yukinori Isomura, Nobuki Takada, Yoritsuna Yamamoto, Makoto Hayashi, Noriyoshi Yamakita, Akihiko Sasaki, Noriyuki Takeda, Jun Takeda, Perrin C. White, Kohei Kaku

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Type 2 11β-hydroxysteroid dehydrogenase encoded by the HSD11B2 gene converts cortisol to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. We investigated the association of HSD11B2 variant with glucose homeostasis. Subjects with normal glucose tolerance (n=585), impaired glucose tolerance (n=202) and type 2 diabetes (n=355) were genotyped for a highly polymorphic CA-repeat polymorphism in the first intron of HSD11B2. Allele and genotype frequencies differed between normal and impaired glucose tolerance (P = 0.0014 and 0.0407, respectively; 4 degree of freedom) or type 2 diabetes (P = 0.0053 and 0.0078), with significant linear trends between the repeat length and the phenotype fraction. In normal subjects, total CA-repeat length was negatively correlated with fasting insulin and HOMA-β. Thus, subjects having more CA repeats are susceptible to developing abnormal glucose tolerance, whereas normal subjects carrying more CA repeats appeared to have frugal characteristics in insulin secretion.

Original languageEnglish (US)
Pages (from-to)671-678
Number of pages8
JournalEndocrine Journal
Volume60
Issue number5
DOIs
StatePublished - 2013

Fingerprint

Glucose Intolerance
Type 2 Diabetes Mellitus
Glucose
Homeostasis
11-beta-Hydroxysteroid Dehydrogenases
Insulin
Cortisone
Gene Frequency
Introns
Glucocorticoids
Hydrocortisone
Fasting
Genotype
Phenotype
Genes

Keywords

  • 11ß-hydroxysteroid dehydrogenase type 2
  • Cortisol
  • Cortisone
  • Insulin
  • Pancreas

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Mune, T., Suwa, T., Morita, H., Isomura, Y., Takada, N., Yamamoto, Y., ... Kaku, K. (2013). Longer HSD11B2 CA-repeat in impaired glucose tolerance and type 2 diabetes. Endocrine Journal, 60(5), 671-678. https://doi.org/10.1507/endocrj.EJ12-0108

Longer HSD11B2 CA-repeat in impaired glucose tolerance and type 2 diabetes. / Mune, Tomoatsu; Suwa, Tetsuya; Morita, Hiroyuki; Isomura, Yukinori; Takada, Nobuki; Yamamoto, Yoritsuna; Hayashi, Makoto; Yamakita, Noriyoshi; Sasaki, Akihiko; Takeda, Noriyuki; Takeda, Jun; White, Perrin C.; Kaku, Kohei.

In: Endocrine Journal, Vol. 60, No. 5, 2013, p. 671-678.

Research output: Contribution to journalArticle

Mune, T, Suwa, T, Morita, H, Isomura, Y, Takada, N, Yamamoto, Y, Hayashi, M, Yamakita, N, Sasaki, A, Takeda, N, Takeda, J, White, PC & Kaku, K 2013, 'Longer HSD11B2 CA-repeat in impaired glucose tolerance and type 2 diabetes', Endocrine Journal, vol. 60, no. 5, pp. 671-678. https://doi.org/10.1507/endocrj.EJ12-0108
Mune T, Suwa T, Morita H, Isomura Y, Takada N, Yamamoto Y et al. Longer HSD11B2 CA-repeat in impaired glucose tolerance and type 2 diabetes. Endocrine Journal. 2013;60(5):671-678. https://doi.org/10.1507/endocrj.EJ12-0108
Mune, Tomoatsu ; Suwa, Tetsuya ; Morita, Hiroyuki ; Isomura, Yukinori ; Takada, Nobuki ; Yamamoto, Yoritsuna ; Hayashi, Makoto ; Yamakita, Noriyoshi ; Sasaki, Akihiko ; Takeda, Noriyuki ; Takeda, Jun ; White, Perrin C. ; Kaku, Kohei. / Longer HSD11B2 CA-repeat in impaired glucose tolerance and type 2 diabetes. In: Endocrine Journal. 2013 ; Vol. 60, No. 5. pp. 671-678.
@article{4ebb5f61904c452ba048683a46a2ad02,
title = "Longer HSD11B2 CA-repeat in impaired glucose tolerance and type 2 diabetes",
abstract = "Type 2 11β-hydroxysteroid dehydrogenase encoded by the HSD11B2 gene converts cortisol to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. We investigated the association of HSD11B2 variant with glucose homeostasis. Subjects with normal glucose tolerance (n=585), impaired glucose tolerance (n=202) and type 2 diabetes (n=355) were genotyped for a highly polymorphic CA-repeat polymorphism in the first intron of HSD11B2. Allele and genotype frequencies differed between normal and impaired glucose tolerance (P = 0.0014 and 0.0407, respectively; 4 degree of freedom) or type 2 diabetes (P = 0.0053 and 0.0078), with significant linear trends between the repeat length and the phenotype fraction. In normal subjects, total CA-repeat length was negatively correlated with fasting insulin and HOMA-β. Thus, subjects having more CA repeats are susceptible to developing abnormal glucose tolerance, whereas normal subjects carrying more CA repeats appeared to have frugal characteristics in insulin secretion.",
keywords = "11{\ss}-hydroxysteroid dehydrogenase type 2, Cortisol, Cortisone, Insulin, Pancreas",
author = "Tomoatsu Mune and Tetsuya Suwa and Hiroyuki Morita and Yukinori Isomura and Nobuki Takada and Yoritsuna Yamamoto and Makoto Hayashi and Noriyoshi Yamakita and Akihiko Sasaki and Noriyuki Takeda and Jun Takeda and White, {Perrin C.} and Kohei Kaku",
year = "2013",
doi = "10.1507/endocrj.EJ12-0108",
language = "English (US)",
volume = "60",
pages = "671--678",
journal = "Endocrine Journal",
issn = "0918-8959",
publisher = "Japan Endocrine Society",
number = "5",

}

TY - JOUR

T1 - Longer HSD11B2 CA-repeat in impaired glucose tolerance and type 2 diabetes

AU - Mune, Tomoatsu

AU - Suwa, Tetsuya

AU - Morita, Hiroyuki

AU - Isomura, Yukinori

AU - Takada, Nobuki

AU - Yamamoto, Yoritsuna

AU - Hayashi, Makoto

AU - Yamakita, Noriyoshi

AU - Sasaki, Akihiko

AU - Takeda, Noriyuki

AU - Takeda, Jun

AU - White, Perrin C.

AU - Kaku, Kohei

PY - 2013

Y1 - 2013

N2 - Type 2 11β-hydroxysteroid dehydrogenase encoded by the HSD11B2 gene converts cortisol to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. We investigated the association of HSD11B2 variant with glucose homeostasis. Subjects with normal glucose tolerance (n=585), impaired glucose tolerance (n=202) and type 2 diabetes (n=355) were genotyped for a highly polymorphic CA-repeat polymorphism in the first intron of HSD11B2. Allele and genotype frequencies differed between normal and impaired glucose tolerance (P = 0.0014 and 0.0407, respectively; 4 degree of freedom) or type 2 diabetes (P = 0.0053 and 0.0078), with significant linear trends between the repeat length and the phenotype fraction. In normal subjects, total CA-repeat length was negatively correlated with fasting insulin and HOMA-β. Thus, subjects having more CA repeats are susceptible to developing abnormal glucose tolerance, whereas normal subjects carrying more CA repeats appeared to have frugal characteristics in insulin secretion.

AB - Type 2 11β-hydroxysteroid dehydrogenase encoded by the HSD11B2 gene converts cortisol to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. We investigated the association of HSD11B2 variant with glucose homeostasis. Subjects with normal glucose tolerance (n=585), impaired glucose tolerance (n=202) and type 2 diabetes (n=355) were genotyped for a highly polymorphic CA-repeat polymorphism in the first intron of HSD11B2. Allele and genotype frequencies differed between normal and impaired glucose tolerance (P = 0.0014 and 0.0407, respectively; 4 degree of freedom) or type 2 diabetes (P = 0.0053 and 0.0078), with significant linear trends between the repeat length and the phenotype fraction. In normal subjects, total CA-repeat length was negatively correlated with fasting insulin and HOMA-β. Thus, subjects having more CA repeats are susceptible to developing abnormal glucose tolerance, whereas normal subjects carrying more CA repeats appeared to have frugal characteristics in insulin secretion.

KW - 11ß-hydroxysteroid dehydrogenase type 2

KW - Cortisol

KW - Cortisone

KW - Insulin

KW - Pancreas

UR - http://www.scopus.com/inward/record.url?scp=84878495474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878495474&partnerID=8YFLogxK

U2 - 10.1507/endocrj.EJ12-0108

DO - 10.1507/endocrj.EJ12-0108

M3 - Article

C2 - 23357976

AN - SCOPUS:84878495474

VL - 60

SP - 671

EP - 678

JO - Endocrine Journal

JF - Endocrine Journal

SN - 0918-8959

IS - 5

ER -