Patients with obesity and type 2 diabetes often display high levels of the anti-diabetic factor fibroblast growth factor-21 (FGF21), suggesting that the overproduction of FGF21 may result from increased adiposity in an attempt by white adipose tissue (WAT) to counteract insulin resistance. However, the production of FGF21 diabetes in the absence of WAT has not been examined. In this study, we investigated the effects of lipodystrophy in A-ZIP F-1 mice on FGF21 production in relation to diabetes. A-ZIP F-1 mice displayed high FGF21 plasma levels resulting from enhanced FGF21 mRNA expression in the liver. Concomitant enhancement of FGF21 receptor (FGFR1) and glucose transporter 1 (GLUT-1) mRNA expression was observed in the muscles of A-ZIP F-1 mice. Furthermore, the activation of hypothalamic NPY and AgRP mRNA expression positively correlated with plasma levels of FGF21 but not active ghrelin. Our study demonstrates that an increased FGF21 plasma level in lipodystrophic A-ZIP F-1 mice results mainly from up-regulated liver production but does not suffice to overcome the lipodystrophy-induced severe type 2-diabetes and insulin resistance in the liver linked to the augmented liver fat deposition., A. Špolcová, M. Holubová, B. Mikulášková, V. Nagelová, A. Štofková, Z. Lacinová, J. Jurčovičová, M. Haluzík, L. Maletínská, B. Železná., and Obsahuje bibliografii
Ghrelin and agonists of its re ceptor GHS-R1a are potential substances for the treatment of cachexia. In the present study, we investigated the acute and lo ng-term effects of the GHS-R1a agonist JMV 1843 (H-Aib-DTrp-D-gTrp -CHO) on food intake, body weight and metabolic parameters in lean C57BL/6 male mice. Additionally, we examined stability of JMV 1843 in mouse blood serum. A single subcutaneous injection of JMV 1843 (0.01-10 mg/kg) increased food intake in fed mice in a dose- dependent manner, up to 5-times relative to the saline-treated group (ED 50 =1.94 mg/kg at 250 min). JMV 1843 was stable in mouse serum in vitro for 24 h, but was mostly eliminated from mouse blood after 2 h in vivo . Ten days of treatment with JMV 1843 (subcutaneous administration, 10 or 20 mg/kg/day) significantly increased food intake, body weight and mRNA expression of the orexigenic neuropeptide Y and agouti-related peptide in the medial basal hy pothalamus and decreased the expression of uncoupling protein 1 in brown adipose tissue. Our data suggest that JMV 1843 could have possible future uses in the treatment of cachexia., M. Holubová, ... [et al.]., and Obsahuje seznam literatury
Glucose tolerance, serum insulin, insulin receptors in epididymal fat tissue, circulating total cholesterol and triglyceride concentrations as well as serum prolactin were studied in obese and lean spontaneously hypertensive rats (SHR) of both sexes. Obese animals displayed insulin resistance and elevated insulin and triglyceride concentrations. Moreover, in obese rats the increased mass of epididymal fat tissue was accompanied with decreased capacity of high affinity binding sites of insulin receptors in the tissue plasma membranes. Terguride treatment lowered prolactin serum levels which was accompanied by ameliorated insulin sensitivity in obese animals of both sexes. In addition, terguride treatment decreased serum insulin and triglyceride concentrations in obese females and at the same time enhanced the affinity of high affinity insulin binding sites. Our results show that obesity in SHR is associated with a decreased capacity of insulin receptors and that prolactin may play a role in obesity-induced insulin resistance, particularly in female rats., V. Golda +, M. Ficková, L. Pinterová, J. Jurčovičová, L. Macho, Š. Zórad., and Obsahuje bibliografii