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Exp Clin Endocrinol Diabetes 2009; 117(2): 83-87
DOI: 10.1055/s-2008-1078733
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Genetic Variability of Procolipase Associates with Altered Insulin Secretion in Non-diabetic Caucasians

P. Weyrich 1 , S. Albet 1 , R. Lammers 1 , F. Machicao 1 , A. Fritsche 1 , N. Stefan 1 , H.-U. Häring 1
  • 1Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tübingen, Germany
Further Information

Publication History

received 21.03.2008 first decision 25.04.2008

accepted 15.05.2008

Publication Date:
25 August 2008 (online)

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Abstract

Aims: Procolipase (CLPS) is secreted from the exocrine pancreas into the gastrointestinal tract and becomes proteolytically cleaved into colipase and the pentapeptide enterostatin. While colipase is an indispensable cofactor for pancreatic lipase, enterostatin acts as a hormone that inhibits insulin secretion and confers satiety signals to the brain, thereby restricting further food intake in animal models. As both high fat diet and obesity contribute to insulin resistance, we investigated whether genetic variability of CLPS associates with metabolic traits in non-diabetic humans at diabetes risk.

Methods: Tagging single nucleotide polymorphisms (SNPs) in the human CLPS locus on chr6p21.1 were selected using HapMap data. 498 humans, phenotyped for different glucose and lipid metabolic traits, were genotyped by bidirectional sequencing and multivariate linear regression analyses were undertaken.

Results: 2 tagging SNPs (rs3748050 in the Kozak sequence: A/G and rs3748051 in intron 1: A/G), covering 100% of CLPS variability including 8 kb of its promoter, were genotyped for association analyses. The minor alleles of both tagging SNPs associated significantly with a reduced insulin secretion (−20.2%, both SNPs) in various estimation models derived from the oral glucose tolerance test (OGTT; rs3748050/51: 30 min C-peptide levels: p=0.001/0.01, insulinogenic index: p=0.02/0.02, AUC C-peptide/AUC glucose: p=0.01/0.01) after adjustment for relevant covariates. No significant associations with fasting total cholesterol (c), HDL-c, LDL-c, triglycerides and free fatty acids were found (all p > 0.11).

Conclusions: CLPS genetic variability associates with insulin secretory function in non-diabetic humans and may represent a novel candidate gene for development of type 2 diabetes.

Key words

type 2 diabetes - genetic association study - procolipase - insulin secretion - insulin sensitivity - enterostatin

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Correspondence

P. WeyrichMD 

Department of Internal Medicine

Division of Endocrinology

Diabetology

Vascular Disease

Nephrology and Clinical Chemistry

University of Tübingen

Germany

University of Tübingen

Otfried-Müller-Str. 10

72076 Tübingen

Germany

Phone: +49/7071/298 27 08

Fax: +49/7071/29 31 88

Email: peter.weyrich@med.uni-tuebingen.de

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