title: The perilipin 2 (PLIN2) gene Ser251Pro missense mutation is associated with reduced insulin secretion and increased insulin sensitivity in Italian obese subjects.
abstract: Perilipin 2 (PLIN2), a member of the family of perilipin lipid droplets coating proteins, is very widely expressed. The Ser251Pro (rs35568725) missense mutation in exon 6 of PLIN2 gene was previously associated with increased lipid accumulation, decreased lipolysis and increased number of small lipid droplets per cell. Furthermore, the Pro251 mutation was associated with decreased plasma triglyceride and very low density lipoprotein concentrations in population studies. The aim of this study was to evaluate the effect of the Ser251Pro mutation of PLIN2 gene in a cohort with a higher predisposition to obesity-associated metabolic alterations, such as insulin resistance, decreased insulin-secretion, hyperglycaemia, and dyslipidaemia.
  
  
  
  A large cohort (N = 1692) of Italian obese subjects (mean body mass index = 41 kg/m(2) ) was genotyped for the Ser251Pro mutation. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance and of insulin secretion were also calculated. Clinical and biochemical parameters were collected for all participants.
  
  
  
  We observed that insulin concentration was significantly reduced at 120 min after the administration of glucose in Pro251 allele carriers, whereas glucose levels were similar in Pro251 allele carriers and non-carriers throughout the OGTT. Furthermore, the CIR120 index of insulin secretion was significantly lower (P < 0.035) and the ISI index of insulin-sensitivity was significantly higher (P < 0.031) in carriers of the Pro251 allele. When we analysed men and women separately to test for gender-specific associations, we observed that in women insulin levels were significantly lower in Pro251 allele carriers compared with wild-type subjects throughout the whole OGTT. In men, we confirmed a significant reduction in insulin concentration only at 120 min after the OGTT. No significant differences between genotype groups regarding triglyceride levels and anyother clinical and metabolic parameters were observed.
  
  
  
  We observed a strong significant association between the PLIN2 Pro251 mutation and lower insulin secretion associated with an increased insulin sensitivity. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Sentinelli
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Danila
authors.initials: D
authors.lastname: Capoccia
authors.affiliation: Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Incani
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bertoccini
authors.affiliation: Institute of Cardiology, Catholic University, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Severino
authors.affiliation: Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Pani
authors.affiliation: Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Manconi
authors.affiliation: Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Efisio
authors.initials: E
authors.lastname: Cossu
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Frida
authors.initials: F
authors.lastname: Leonetti
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.|Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Marco G
authors.initials: MG
authors.lastname: Baroni
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D003920:Diabetes Mellitus / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D009765:Obesity / Q000150:complications*; D000070780:Perilipin-2 / Q000235:genetics*; D011379:Prognosis
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D000070780:Perilipin-2; C000602982:PLIN2 protein, human; C517652:hemoglobin A1c protein, human
keywords: insulin secretion; insulin sensitivity; mutation; obesity