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Claire L Wood, Ondrej Soucek, Sze C Wong, Farasat Zaman, Colin Farquharson, Lars Savendahl and S Faisal Ahmed

et al. 1992 ). GCs also act systemically to inhibit the pulsatile secretion of GH from the anterior pituitary gland by increasing somatostatin tone ( Mazziotti & Giustina 2013 ). Animal models of GIO- and GC-induced growth retardation It is

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Clare M Reynolds and Mark H Vickers

Introduction Data from epidemiological, clinical and experimental animal models has clearly demonstrated that the risk for developing abnormalities of metabolic and cardiovascular homeostasis and reproductive disorders in adult life is

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Mark E Peterson

transitioning from a subclinical stage to overt hyperthyroidism as the automatous thyroid nodules increase in size ( Wakeling et al . 2007 , 2011 , Broome & Peterson 2014 , Peterson & Broome 2014 a ). As such, this disease offers a unique animal model for

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KL Hull and S Harvey

GH exerts pleiotropic effects on growth and metabolism through the GH receptor. A deficiency in the GH receptor gene is thus associated with GH resistance and dwarfism. Complete GH resistance in humans, or Laron syndrome, has been associated with numerous inherited defects in the GH receptor, including point mutations, complete or partial gene deletions, and splice site alterations. Analysis of the GH receptor genes of these patients has provided considerable insight into structure-function relationships of the GH receptor. However, the relative rarity of this disease and the obvious difficulties involved in human research have prompted a search for an animal model of GH resistance. Numerous models have been proposed, including the sex-linked dwarf chicken, the guinea pig, and the Laron mouse. In this review, the characteristics and etiology of Laron syndrome and these animal models will be discussed. The insight provided by these disorders into the roles and mechanism of action of GH will also be reviewed.

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BD Rodgers, M Bernier and MA Levine

Adipocyte beta-adrenergic sensitivity is compromised in animal models of obesity and type 2 diabetes. Although changes in the membrane concentrations of G-protein alpha subunits (Galpha) have been implicated, it remains to be determined how these changes are affected by insulin resistance in the different animal models. Because previous studies used young animals, we measured the concentrations of Galpha and Gbeta subunits in epididymal fat from aged (48 weeks old) db/db mice and from their lean littermates to more closely reproduce the model of type 2 diabetes mellitus. Levels of immunoreactive Galphas, Galphai(1/2), Galphao and Galphaq/11 were all significantly greater in adipocyte membranes from the db/db mice than in membranes from their lean non-diabetic littermate controls. Levels of Galphai(1) and Galphai(2) were also individually determined and although they appeared to be slightly higher in db/db membranes, these differences were not significant. Although the levels of both Galphas isoforms were elevated, levels of the 42 and 46 kDa proteins rose by approximately 42% and 20% respectively, indicating differential protein processing of Galphas. By contrast, levels of Galphai3 were similar in the two groups. The levels of common Gbeta and Gbeta2 were also elevated in db/db mice, whereas Gbeta1 and Gbeta4 levels were not different. To determine whether these changes were due to insulin resistance per se or to elevated glucocorticoid production, G-protein subunit levels were quantified in whole cell lysates from 3T3-L1 adipocytes that were stimulated with different concentrations of either insulin or corticosterone. Although none of the subunit levels was affected by insulin, the levels of both Galphas isoforms were increased equally by corticosterone in a concentration-dependent manner. Since glucocorticoids are known regulators of Galphas gene expression in many cell types and in adipocytes from diabetic rodents, the results presented herein appear to more accurately reflect diabetic pathophysiology than do those of previous studies which report a decrease in Galphas levels. Taken together, these results indicate that most of the selective changes in G-protein subunit production in adipocytes from this animal model of type 2 diabetes may not be due to diminished insulin sensitivity, but may be due to other endocrine or metabolic abnormalities associated with the diabetic phenotype.

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Richard W Nelson and Claudia E Reusch

with diabetes mellitus . Journal of Veterinary Internal Medicine 26 1519 (abstract) doi:10.1111/jvim.12000 ) This paper forms part of a thematic review series on Animal Models of Disease. The Guest Editor for this section was Alan Conley

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D Sömjen, Y Amir-Zaltsman, G Mor, B Gayer, S Lichter, G Barnard and F Kohen

Abstract

Previous studies indicated that the anti-idiotypic antibody (clone 1D5) significantly increased the specific activity of creatine kinase (CK) activity in the rat uterus, and in vitro in skeletal cells capable of responding to oestradiol (E2), suggesting that the antibody has oestrogenic-like activity. Moreover, the F(ab′)2 dimer of clone 1D5 acted like an antagonist and completely inhibited the increase in CK specific activity by either E2 or clone 1D5 in these skeletal cells. In the present study, we examined the in vivo effects of clone 1D5 and its proteolytic fragment, the F(ab′)2 dimer, E2 and dihydrotestosterone (DHT) on CK specific activity in the epiphyseal cartilage, diaphyseal bone, uterus, prostate, thymus and pituitary of immature or gonadectomized female and male rat animal models. In the intact immature animals, clone 1D5 caused an increase in CK in all organs of the female except in the pituitary. In the diaphyseal bone and prostate of male rats there was no stimulation by 1D5. The CK response in the uterus, epiphysis, and diaphysis of immature female rats was dose-dependent and was blocked by either the anti-oestrogen tamoxifen or the F(ab′)2 dimer of clone 1D5. E2, DHT, as well as clone 1D5, stimulated CK specific activity in both the diaphysis and epiphysis of ovariectomized female and castrated male rats, whereas sex specificity in the CK response was observed also in the uterus and the prostate of gonadectomized animals. Collectively, these results suggest that, as in cell culture, an intact antibody is necessary for the observed stimulation of CK specific activity and the F(ab′)2 dimer can act as an antagonist. Furthermore, the observed biological effects of clone 1D5 which are absolutely parallel to E2, imply that the anti-idiotypic antibody is able to penetrate the cell and reach the nuclear oestrogen receptor and transduces a signal to the nucleus, by as yet uncharacterized mechanisms.

Journal of Endocrinology (1996) 149, 305–312

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G Üçkaya, P Delagrange, A Chavanieu, G Grassy, M-F Berthault, A Ktorza, E Cerasi, G Leibowitz and N Kaiser

Introduction Type 2 diabetes results from failure to increase insulin secretion in the face of insulin resistance ( Cerasi 1995 , Kahn 2003 ). Studies in humans and animal models of type 2 diabetes show marked β-cell dysfunction

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Sehee Kim, Minho Moon and Seungjoon Park

cellular and animal models, such as stroke ( Li et al . 2009 ), cholinergic ablation ( Perry et al . 2002 a ), kainic acid-induced CA3 hippocampal loss ( During et al . 2003 ), and peripheral neuropathy ( Perry et al . 2007 ). In this study, we showed