Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and type 2 diabetes susceptibility.
نویسندگان
چکیده
AIMS Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to type 2 diabetes in humans. METHODS Four potentially functional variants in the coding region of the DRD2/ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for type 2 diabetes susceptibility in up to 25 000 people (8148 with type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis. RESULTS rs1800497 at the DRD2/ANKK1 locus was associated with a significantly increased risk for type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); P = 4.1*10⁴) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); P = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women (P = 5.5*10⁴) but again not in men (P = 0.34). CONCLUSION The present data identify DRD2/ANKK1 as a potential sex-specific type 2 diabetes susceptibility gene.
منابع مشابه
The effect of ghrelin on Kiss-1 and KissR gene transcription and insulin secretion in rat islets of Langerhans and CRI-D2 cell line
Objective(s): Ghrelin is a peptide hormone that has been shown to have numerous central and peripheral effects. The central effects including GH secretion, food intake, and energy homeostasis are partly mediated by Kiss1- KissR signaling pathway. Ghrelin and its receptor are also expressed in the pancreatic islets. Ghrelin is one of the key metabolic factors controlling insulin secretion from t...
متن کاملModulatory Effects of Dopamine D2 Receptors on Spreading Depression in Rat Somatosensory Neocortex
Introduction: Spreading depression (SD) is a propagating wave of depolarization followed by depression of the neuroglial activities and can modulate extracellular dopamine concentrations in the neocortex. It has been shown that the dopaminergic system plays a role in migraine. SD has been suggested as a critical phenomenon in the pathophysiology of migraine. The aim of this study was to investi...
متن کاملThe role of noggin in regulation of high glucose-induced apoptosis and insulin secretion in INS-1 rat beta cells
Objective(s):The purpose of this study was to investigate the effects of Noggin on high glucose-induced apoptosis and insulin secretion in pancreatic beta cells. Materials and Methods: Different concentrations of glucose were used to examine their effects on INS-1 rat beta cells in vitro. When specific siRNA targeting Noggin and recombinant Noggin were added, apoptosis and insulin secretion wer...
متن کاملSurvey on the interaction effect of dopamine D2 receptor antagonist on morphine-induced polycystic ovary syndrome in rat
Background and Objective: Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in premenopausal women. Opioid drugs, including morphine are effective inducers of the PCOS. Hyperprolactinemia also increases the likelihood of this complication. The dopamine, the inhibitor of prolactin secretion, has receptors in the ovarian tissue. In this study, metoclopra...
متن کاملارتباط پلی مورفیسم3'UTR(C>A) از ژن گیرنده (IGF2R)IGF2 با شاخص‌های مقاومت به انسولین در بیماران مبتلا به دیابت نوع2 و افراد غیردیابتی
Background and objective: Association of 6q loci, where IGF2R gene is located, with insulin resistance has been well established. In this study, relationship between 3'UTR and type 2 diabetes and insulin resistance indices in non diabetic subjects was investigated. Materials and Methods: 350 participants (175 diabetic type 2 patient and 175 non-diabetic individuals) were entered in this study. ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Diabetic medicine : a journal of the British Diabetic Association
دوره 31 8 شماره
صفحات -
تاریخ انتشار 2014