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Doron Weinstein
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Rive Sarfstein
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Zvi Laron Department of Human Molecular Genetics and Biochemistry, Endocrinology and Diabetes Research Unit, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel

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Haim Werner
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, and experimental evidence suggests an association between IGF system components and PCa development (1) . In particular, a close functional connection has been identified between the IGF1 receptor (IGF1R), a transmembrane heterotetramer primarily

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R Solomon-Zemler Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

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L Basel-Vanagaite Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Raphael Recanati Genetic Institute, Rabin Medical Center – Beilinson Hospital, Petach Tikva, Israel
Felsenstein Medical Research Center, Petach Tikva, Israel
Pediatric Genetics, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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D Steier Day Hospitalization Department, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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S Yakar David B. Kriser Dental Center, Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York, USA

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E Mel Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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M Phillip Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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L Bazak Raphael Recanati Genetic Institute, Rabin Medical Center – Beilinson Hospital, Petach Tikva, Israel

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D Bercovich Tel-Hai College, Tel-Hai, Israel

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H Werner Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Shalom and VardaYoran Institute for Human Genome Research, Tel Aviv University, Tel Aviv, Israel

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L de Vries Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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mutation of the IGF1 receptor gene in a patient with severe pre- and postnatal growth failure and congenital malformations . European Journal of Endocrinology 2012 168 K1 – K7 . ( doi:10.1530/EJE-12-0701 ) 18 Liu JP Baker J Perkins AS

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Marie Reeberg Sass Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Nicolai Jacob Wewer Albrechtsen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark

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Jens Pedersen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Endocrinology and Nephrology, Nordsjællands University Hospital, Hillerød, Denmark

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Kristine Juul Hare Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Nis Borbye-Lorenzen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark

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Katalin Kiss Department of Pathology, Rigshospitalet, Copenhagen, Denmark

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Tina Vilsbøll Steno Diabetes Center Copenhagen, Gentofte, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Filip Krag Knop Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Gentofte, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Steen Seier Poulsen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Niklas Rye Jørgensen Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Jens Juul Holst Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Cathrine Ørskov Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Bolette Hartmann Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Objective:

Parathyroid hormone (PTH) is a key hormone in regulation of calcium homeostasis and its secretion is regulated by calcium. Secretion of PTH is attenuated during intake of nutrients, but the underlying mechanism(s) are unknown. We hypothesized that insulin acts as an acute regulator of PTH secretion.

Methods:

Intact PTH was measured in plasma from patients with T1D and matched healthy individuals during 4-h oral glucose tolerance tests (OGTT) and isoglycemic i.v. glucose infusions on 2 separate days. In addition, expression of insulin receptors on surgical specimens of parathyroid glands was assessed by immunochemistry (IHC) and quantitative PCR (qPCR).

Results:

The inhibition of PTH secretion was more pronounced in healthy individuals compared to patients with T1D during an OGTT (decrementalAUC0–240min: −5256 ± 3954 min × ng/L and −2408 ± 1435 min × ng/L, P = 0.030). Insulin levels correlated significantly and inversely with PTH levels, also after adjusting for levels of several gut hormones and BMI (P = 0.002). Expression of insulin receptors in human parathyroid glands was detected by both IHC and qPCR.

Conclusion:

Our study suggests that insulin may act as an acute regulator of PTH secretion in humans.

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A J Varewijck Erasmus MC, Department of Internal Medicine, Division of Endocrinology, 's-Gravendijkwal 230, Room D-443, 3015 CE Rotterdam, The Netherlands

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A J van der Lely Erasmus MC, Department of Internal Medicine, Division of Endocrinology, 's-Gravendijkwal 230, Room D-443, 3015 CE Rotterdam, The Netherlands

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S J C M M Neggers Erasmus MC, Department of Internal Medicine, Division of Endocrinology, 's-Gravendijkwal 230, Room D-443, 3015 CE Rotterdam, The Netherlands

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S W J Lamberts Erasmus MC, Department of Internal Medicine, Division of Endocrinology, 's-Gravendijkwal 230, Room D-443, 3015 CE Rotterdam, The Netherlands

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L J Hofland Erasmus MC, Department of Internal Medicine, Division of Endocrinology, 's-Gravendijkwal 230, Room D-443, 3015 CE Rotterdam, The Netherlands

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J A M J L Janssen Erasmus MC, Department of Internal Medicine, Division of Endocrinology, 's-Gravendijkwal 230, Room D-443, 3015 CE Rotterdam, The Netherlands

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are still used to assess IGF1 bioactivity has been the lack of reliable assays to measure IGF1 bioactivity. An IGF1 receptor (IGF1R)-specific kinase receptor activation (KIRA) assay has been developed as an alternative method to evaluate circulating

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B Shahida Department of Clinical Sciences, Genomics, Diabetes and Endocrinology, Lund University, Malmö, Sweden
Department of Diabetes and Endocrinology, Skåne University Hospital, Malmö, Sweden

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P Sahlstrand Johnson Department of Oto-Rhino-Laryngology, Skåne University Hospital, Malmö, Sweden
Department of Clinical Sciences, Lund University, Malmö, Sweden

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R Jain Department of Clinical Sciences, Genomics, Diabetes and Endocrinology, Lund University, Malmö, Sweden

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H Brorson Department of Clinical Sciences, Lund University, Malmö, Sweden
Department of Plastic Surgery, Skåne University Hospital, Malmö, Sweden

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P Åsman Department of Clinical Sciences Malmö, Ophthalmology, Lund University, Malmö, Sweden
Department of Ophthalmology, Skåne University Hospital, Malmö, Sweden

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M Lantz Department of Clinical Sciences, Genomics, Diabetes and Endocrinology, Lund University, Malmö, Sweden
Department of Diabetes and Endocrinology, Skåne University Hospital, Malmö, Sweden

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T Planck Department of Clinical Sciences, Genomics, Diabetes and Endocrinology, Lund University, Malmö, Sweden
Department of Diabetes and Endocrinology, Skåne University Hospital, Malmö, Sweden

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as an autoantigen and is expressed by both preadipocytes and adipocytes in orbital tissue ( 1 , 2 ) as well as in the thyroid. Other autoantigens, such as the insulin-like growth factor 1 (IGF-1) receptor have been suggested to be involved in the

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Rossella Cannarella Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Andrea Crafa Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Sandro La Vignera Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Rosita A Condorelli Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Aldo E Calogero Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Zebrafish ( 5 ). Furthermore, we have recently shown that the growth hormone receptor (GHR) and the IGF1 receptor (IGF1R) are both expressed in the Gn11 and the GT1-7 cell lines. The incubation with either GH or IGF1 stimulated Gn11 cell migration and GnRH

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A V Dreval
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I V Trigolosova
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I V Misnikova
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Y A Kovalyova
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R S Tishenina
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I A Barsukov
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A V Vinogradova
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B H R Wolffenbuttel Moscow Regional Scientific Research Clinical Institute, Department of Endocrinology, 61/2 Shepkina str., 129110 Moscow, Russia

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between plasma GH and IGF1 concentrations and measures of insulin resistance has been reported (6) . On the other hand, IGF1 has a positive effect on hybrid insulin/IGF1 receptors in adipose tissue, muscles and hepatocytes, which ensures its insulin

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Giovanni Tulipano Unit of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy

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receptor, insulin- and IGF-1 receptors in primate pituitary cells, whereas it did not alter GnRH receptor and GHRH receptor expression ( 46 ). It is worth remarking that insulin receptor and IGF-1 receptor are expected to activate the PI3K-mTOR pathway in

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Xiaohui Qi Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Ping He Shanghai Hospital Link Center, Shanghai Hospital Development Center, Shanghai, China

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Huayan Yao Computer Net Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Huanhuan Sun Wonders Information Co. Ltd, Shanghai, China

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Jiying Qi Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Min Cao Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Bin Cui Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Guang Ning Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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because it is structurally modified ( 20 , 21 ). In addition to activating the insulin receptor cascade response, long-acting insulin analogs can also affect the IGF-1 receptor cascade response ( 22 ). And there is evidence from Alvaro’s study that IGF-1

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Rossella Cannarella Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Teresa Mattina Genetics, University of Catania, Catania, Italy

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Rosita A Condorelli Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Laura M Mongioì Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Giuseppe Pandini Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Sandro La Vignera Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Aldo E Calogero Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Gosset P Sanlaville D Thauvin-Robinet C Cusin V Lionnais S Callier P Khau Van Kien P Prenatal overgrowth and mosaic trisomy 15q25-qter including the IGF1 receptor gene . Prenatal Diagnosis 2004 24 393 – 395 . ( doi:10

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