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Liselotte Fransson Department of Clinical Science and Education, Division of Drug Research, Center of Medical Image Science and Visualization, Department of Biochemistry and Molecular Biology, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden

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Stephanie Franzén Department of Clinical Science and Education, Division of Drug Research, Center of Medical Image Science and Visualization, Department of Biochemistry and Molecular Biology, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden
Department of Clinical Science and Education, Division of Drug Research, Center of Medical Image Science and Visualization, Department of Biochemistry and Molecular Biology, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden

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Victoria Rosengren Department of Clinical Science and Education, Division of Drug Research, Center of Medical Image Science and Visualization, Department of Biochemistry and Molecular Biology, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden

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Petra Wolbert Department of Clinical Science and Education, Division of Drug Research, Center of Medical Image Science and Visualization, Department of Biochemistry and Molecular Biology, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden

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Åke Sjöholm Department of Clinical Science and Education, Division of Drug Research, Center of Medical Image Science and Visualization, Department of Biochemistry and Molecular Biology, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden
Department of Clinical Science and Education, Division of Drug Research, Center of Medical Image Science and Visualization, Department of Biochemistry and Molecular Biology, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden

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Henrik Ortsäter Department of Clinical Science and Education, Division of Drug Research, Center of Medical Image Science and Visualization, Department of Biochemistry and Molecular Biology, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden

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conclude that the increased demand on insulin secretion from the pancreatic islets, in this model with hyperglycemia and insulin resistance, is followed by an adaptation – not only via an increase in the number of β-cells and thus islet size – but also via

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Malathi Srinivasan
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Paul Mitrani
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Gigani Sadhanandan
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Catherine Dodds
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Suhad Shbeir-ElDika
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Shanthie Thamotharan Department of Biochemistry, Department of Pediatrics, Department of Medicine, Diabetes and Endocrinology Center of Western New York, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York at Buffalo, 140 Farber Hall, 3435 Main Street, Buffalo, New York 14214, USA

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Hussam Ghanim Department of Biochemistry, Department of Pediatrics, Department of Medicine, Diabetes and Endocrinology Center of Western New York, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York at Buffalo, 140 Farber Hall, 3435 Main Street, Buffalo, New York 14214, USA

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Paresh Dandona Department of Biochemistry, Department of Pediatrics, Department of Medicine, Diabetes and Endocrinology Center of Western New York, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York at Buffalo, 140 Farber Hall, 3435 Main Street, Buffalo, New York 14214, USA
Department of Biochemistry, Department of Pediatrics, Department of Medicine, Diabetes and Endocrinology Center of Western New York, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York at Buffalo, 140 Farber Hall, 3435 Main Street, Buffalo, New York 14214, USA

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Sherin U Devaskar Department of Biochemistry, Department of Pediatrics, Department of Medicine, Diabetes and Endocrinology Center of Western New York, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York at Buffalo, 140 Farber Hall, 3435 Main Street, Buffalo, New York 14214, USA

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Mulchand S Patel
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isocaloric and isonitrogenous milk formula ( Patel & Srinivasan 2002 , Srinivasan et al . 2003 ). The immediate onset of hyperinsulinemia in the HC pups correlates with several adaptations in pancreatic β cells including the autonomic regulation of insulin

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Toshihiro Sugiyama Department of Orthopaedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Yamaguchi 755-8505, Japan
Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan

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Toshiaki Takaki Department of Orthopaedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Yamaguchi 755-8505, Japan
Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan

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Kenya Sakanaka Department of Orthopaedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Yamaguchi 755-8505, Japan
Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan

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Hiroki Sadamaru Department of Orthopaedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Yamaguchi 755-8505, Japan
Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan

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Koji Mori Department of Orthopaedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Yamaguchi 755-8505, Japan
Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan

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Yoshihiko Kato Department of Orthopaedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Yamaguchi 755-8505, Japan
Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan

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Toshihiko Taguchi Department of Orthopaedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Yamaguchi 755-8505, Japan
Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan

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Takashi Saito Department of Orthopaedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Yamaguchi 755-8505, Japan
Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan

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mineral formation de novo ( Hunter et al. 1996 ) and mice lacking osteopontin have larger mineral size ( Boskey et al. 2002 ) and stiffer bone tissue ( Duvall et al. 2007 ). Compensatory adaptation of warfarin

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T Clark Brelje Department of Genetics, Cell Biology and Development, University of Minnesota Medical School, 6-160 Jackson Hall, 321 Church Street, SE, Minneapolis, Minnesota 55455, USA

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Nicholas V Bhagroo Department of Genetics, Cell Biology and Development, University of Minnesota Medical School, 6-160 Jackson Hall, 321 Church Street, SE, Minneapolis, Minnesota 55455, USA

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Laurence E Stout Department of Genetics, Cell Biology and Development, University of Minnesota Medical School, 6-160 Jackson Hall, 321 Church Street, SE, Minneapolis, Minnesota 55455, USA

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Robert L Sorenson Department of Genetics, Cell Biology and Development, University of Minnesota Medical School, 6-160 Jackson Hall, 321 Church Street, SE, Minneapolis, Minnesota 55455, USA

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lipids induces a further adaptation in the islets. By late pregnancy, insulin secretion is less sensitive to glucose stimulation and becomes more dependent on the presence of fatty acids. This situation allows the maintenance of elevated insulin secretion

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Gabriel F Anhê
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Tatiane C A Nogueira
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José E Nicoletti-Carvalho
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Camilo Lellis-Santos
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Helena C Barbosa
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José Cipolla-Neto
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José R Bosqueiro
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Antonio C Boschero
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Silvana Bordin
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Introduction In pancreatic β-cells, the most prominent effect attributed to Janus kinase/signal transducer and activator of transcription 5 (JAK/STAT5) signaling pathway is the functional adaptation induced by placental lactogens (PL

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I Avril
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B Blondeau
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B Duchene
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P Czernichow
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B Breant
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We investigated the cellular mechanisms responsible for the inability of 8-month-old previously malnourished (PM) females to adapt their beta-cell mass during pregnancy. The evolution during pregnancy of beta-cell fraction, size and proliferation was studied. At day 21 of pregnancy beta-cell fraction increased less in PM than in control females, compared with their non-pregnant values. A slight beta-cell hypertrophy was observed during pregnancy in both groups. In control females, beta-cell 5-bromo-2'-deoxyuridine (BrdU) labelling index (LI) increased from 0.07+/-0.04% before pregnancy to 1.13+/-0.20% at day 12 and decreased thereafter to reach again basal levels at day 21. In PM females, beta-cell proliferation rate was decreased at day 12 (0.74+/-0.15%, P<0.05) but similar to controls at all other stages studied. Separate analysis of the head and tail parts of the pancreas in control animals revealed that the beta-cell fraction during pregnancy increased more in the head than in the tail; similarly, BrdU LI increased 20-fold in the head and 10-fold in the tail, compared with non-pregnant values. In PM females, no adaptation of beta-cell fraction could be observed in the head, where BrdU LI was decreased by half at day 12 of pregnancy. In PM females the lactogenic activity was twice that of controls at day 12 whereas all beta-cells expressed the prolactin receptor. In conclusion, perinatal malnutrition impairs subsequent adaptation to pregnancy by decreasing beta-cell proliferation in the head of the pancreas at a critical time during pregnancy.

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M Quinkler
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H Troeger
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E Eigendorff
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C Maser-Gluth
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A Stiglic
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W Oelkers
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V Bahr
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S Diederich
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The 11beta-hydroxysteroid dehydrogenases (11beta-HSDs) convert cortisol to its inactive metabolite cortisone and vice versa. 11beta-HSD type 1 (11beta-HSD-1) functions as a reductase in vivo, regulating intracellular cortisol levels and its access to the glucocorticoid receptor. In contrast, 11beta-HSD-2 only mediates oxidation of natural glucocorticoids, and protects the mineralocorticoid receptor from high cortisol concentrations. We investigated the in vivo and in vitro effects of ACTH on the recently characterized 11beta-HSDs in guinea pig liver and kidney. Tissue slices of untreated guinea pigs were incubated with (3)H-labelled cortisol or cortisone and ACTH(1-24) (10(-10) and 10(-9) mol/l). The 11beta-HSD activities in liver and kidney slices were not influenced by in vitro incubation with ACTH(1-24). In addition, guinea pigs were treated with ACTH(1-24) or saline injections s.c. for 3 days. Liver and kidney tissue slices of these animals were incubated with (3)H-labelled cortisol or cortisone. In vivo ACTH treatment significantly increased reductase and decreased oxidase activity in liver and kidney. Furthermore, 11beta-HSD-1 activity assessed by measurement of the urinary ratio of (tetrahydrocortisol (THF)+5alphaTHF)/(tetrahydrocortisone) was significantly increased after ACTH treatment compared with the control group. Plasma levels of cortisol, cortisone, progesterone, 17-hydroxyprogesterone and androstenedione increased significantly following in vivo ACTH treatment. The enhanced reductase activity of the hepatic and renal 11beta-HSD-1 is apparently caused by cortisol or other ACTH-dependent steroids rather than by ACTH itself. This may be an important fine regulation of the glucocorticoid tonus for stress adaptation in every organ, e.g. enhanced gluconeogenesis in liver.

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CH Dotman
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F van Herp
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GJ Martens
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BG Jenks
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EW Roubos
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The toad Xenopus laevis is able to adapt its skin color to background light intensity. In this neuroendocrine reflex, the proopiomelanocortin (POMC)-derived peptide alpha-melanophore-stimulating hormone (alphaMSH) is a key regulatory factor. In animals adapting to a black background, release of alphaMSH from the pituitary pars intermedia causes dispersal of melanin in skin melanophores. To investigate the long-term in vivo dynamics of alphaMSH production during black background adaptation, the biosynthetic rate of POMC and the contents of POMC, alphaMSH and the POMC processing enzyme precursor convertase 2 (PC2) have been studied in the pars intermedia using pulse-labeling, Western blot and radioimmunoassay. In control animals, adapted to a white background, the rate of POMC biosynthesis and the POMC content were low, while high alphaMSH and PC2 contents were found. After 1 week of adaptation to a black background, the rate of POMC biosynthesis and the POMC protein content had increased 19- and 3.7-fold respectively. These parameters attained a maximum level (28- and 5. 8-fold higher than control) after 3 weeks and remained at these elevated levels for at least 12 weeks. After 1 week, the pars intermedia content of alphaMSH was only 30% of the control level, but after 6 and 12 weeks, the alphaMSH level had increased to the control level. The PC2 content decreased to 52% of control after 1 week and stabilized after 3 weeks at a level slightly lower than the control value. The results show that during long-term background adaptation a steady-state situation is reached, with a balance between the biosynthesis, enzymatic processing and release of alphaMSH. The in vivo dynamics of the processing enzyme PC2 suggest a parallel storage and release of alphaMSH and mature PC2 in the Xenopus pituitary pars intermedia.

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J S M Cuffe School of Biomedical Science, The University of Queensland, St Lucia, Queensland, Australia
School of Medical Science, Menzies Health Institute Queensland, Griffith University, Gold Coast Campus, Southport, Queensland, Australia

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E L Turton School of Biomedical Science, The University of Queensland, St Lucia, Queensland, Australia

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L K Akison School of Biomedical Science, The University of Queensland, St Lucia, Queensland, Australia

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H Bielefeldt-Ohmann School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia

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K M Moritz School of Biomedical Science, The University of Queensland, St Lucia, Queensland, Australia

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. In turn, this increase in adrenal size at 6 months of age may have contributed to the increased production of Cort as well as aldosterone ( Cuffe et al . 2016 ). The decrease in Mc2r expression at 6 months may be a compensatory adaptation to the

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H Del Zotto
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M I Borelli
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L Flores
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M E García
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C L Gómez Dumm
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A Chicco
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Y B Lombardo
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J J Gagliardino
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successful sustained adaptation to the increased demand of insulin. The concomitant absence of increase in the number of INGAP-positive cells and lack of a neogenetic reaction would support the idea of a stimulatory effect of this peptide upon neogenesis

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