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- Barlind, Anna, 1978, et al.
(författare)
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The growth hormone secretagogue hexarelin increases cell proliferation in neurogenic regions of the mouse hippocampus.
- 2010
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Ingår i: Growth hormone & IGF research. - : Elsevier BV. - 1532-2238 .- 1096-6374. ; 20:1, s. 49-54
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Radiation therapy (RT) to the brain is often used in the treatment of children with different types of malignant diseases affecting the brain. However, RT in childhood may also have severe side effects including impaired brain maturation and intellectual development. For childhood cancer survivors these adverse effects of RT can cause lifelong disability and suffering. Therefore, there is an unmet need to limit late effects after RT. Precursor cells in the subgranular zone of the dentate gyrus (DG) in the hippocampus are particularly sensitive to irradiation (IR). This may be of significance as newly generated neurons in the DG are important for memory and learning. GH secretagogues (GHS) have previously been shown to promote neurogenesis and to have neuroprotective effects. In addition, several parts of the brain, including the hippocampus, have been shown to express the GHS receptor 1a (GHS-R1a). The aim of this study was to evaluate the potential effect of the GHS hexarelin on proliferation and survival of progenitor cells in the hippocampus after brain IR in a mouse model. DESIGN: In the present study, 10-day-old male mice received 6Gy cranial IR. Non-irradiated sham animals were used as controls. We treated one group of irradiated and one sham group with hexarelin (100mug/kg/day) for 28days and used immunohistochemical labeling of bromo-deoxy uridine (BrdU) and phospho-histone H3 of the granular cell layer of the DG to evaluate proliferation and cell survival after IR at postnatal day ten. RESULTS: Our results show that hexarelin significantly increased the number of BrdU-positive cells in the granule cell layer by approximately 50% compared to controls. CONCLUSION: The increased number of BrdU-positive cells in the granule cell layer suggests a partial restoration in the pool of proliferating cells by hexarelin after IR.
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- Burman, Pia, et al.
(författare)
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Large fat and skin necroses after deep subcutaneous injections of a slow-release somatostatin analogue in a woman with acromegaly.
- 2010
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1532-2238 .- 1096-6374. ; Dec, s. 438-440
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Somatostatin analogues are the most commonly used drugs for treatment of acromegaly. Known side effects include gastrointestinal reactions, cholelithiasis, effects on glucose metabolism, and mild reactions at injection sites. We report a patient who developed fat and skin necroses after injections of a depot somatostatin analogue. SUBJECT: A woman with active acromegaly was given deep subcutaneous injections of an extended release formulation of lanreotide at alternate sides of the buttocks on three occasions over a ten week period. The regimen was then discontinued due to gastrointestinal complaints. One month later indurated subcutaneous nodules appeared at both sites. After another two months, the patient presented 10×10cm lesions on the buttocks, with central erythematous zones and, at the site of two injections, a necrotic 5×3cm ulcer. There were no signs of infection or systemic diseases. MRI revealed bilateral fat necroses. A month later, an ulcer developed at the second site. The ulcers were managed conservatively until clear demarcations were obtained, where after surgical revisions were performed. Eight months after the last injection, the wounds could be closed. CONCLUSION: The fat and skin necroses represent a side-effect not previously described after deep subcutaneous injections. Possibly, the patient had an exceptional susceptibility to develop an inflammatory, foreign-body like reaction that hypothetically was aggravated by a sustained anti-angiogenic effect of the compound.
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- Bäck, Karolina, et al.
(författare)
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Changes in insulin and IGF-I receptor expression during differentiation of human preadipocytes
- 2009
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 19:2, s. 101-111
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Tidskriftsartikel (refereegranskat)abstract
- Mature adipocytes originate from fibroblast-like precursor cells, preadipocytes, which differentiate to obtain the characteristics of adipocytes. Our aim was to investigate how differentiation of human preadipocytes affects the distribution of insulin receptors (IR) and IGF-I receptors (IGF-IR) and other cell characteristics. Preadipocytes were differentiated using indomethacine, dexamethasone, isobutyl-methylxantine (IBMX) and high concentration of insulin. Gene expression was quantified by real-time RT-PCT in preadipocytes (PA), differentiated preadipocytes (dPA) and mature adipocytes (mAD). The amount of expressed receptor protein was analyzed using receptor specific ELISAs and Western blot. We also studied DNA synthesis with radiolabeled thymidine incorporation and glucose accumulation with radiolabeled glucose. Differentiation of PA increased gene expression of IR but not IGF-IR, GLUT4, growth hormone receptor (GHR) and adiponectin appeared or increased. In PA and dPA only IR-A was expressed whereas also IR-B was detected in mAD. By Western blot and ELISA, IR and IGF-IR was phosphorylated by their own ligant at 1 nM and in dPA the acitivation of both receptors was stimulated by IGF-I, but not insulin, at 1 nM. Accumulation of glucose in PA was increased by insulin at 10 nM and by IGF-I at 1 nM and 10 nM. DNA synthesis was increased by insulin and IGF-I at 10 nM. In conclusion, both IR and IGF-IR are present in human preadipocytes and adipocytes. Differentiation is characterized by an increased IR/IGF-IR ratio.
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- Chisalita, Simona I., 1972-, et al.
(författare)
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Characterisation of receptors for IGF-I and insulin; evidence for hybrid insulin/IGF-I receptor in human coronary artery endothelial cells
- 2006
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1532-2238 .- 1096-6374. ; 16:4, s. 258-266
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Coronary artery disease is a prevalent cause of morbidity and mortality in diabetes. Little is known about insulin-like growth factor-I receptors (IGF-IR) and insulin receptors (IR) in human coronary endothelium. Our aim was to characterize IGF-IR and IR in human coronary artery endothelial cells (HCAEC). DESIGN: Cultured human coronary artery endothelial cells were used. Gene expression was measured by quantitative real-time RT-PCR analysis and receptor affinity by ligand binding. Receptor protein, phosphorylation of IGF-IR and IR beta-subunit as well as the presence of hybrid insulin receptor/Insulin-like growth factor-I receptor (Hybrid IR/IGF-IR) was analyzed by immunoprecipitation and Western blot. Postreceptor effects of insulin and IGF-I were assed by (3)H-thymidine incorporation. RESULTS: The gene expression of IGF-IR was several folds higher than that of IR. and insulin receptor isoform A (IR-A) was 20-fold more expressed than insulin receptor isoform B (IR-B) in HCAEC. The specific binding of (125)I-IGF-I was higher than that of (125)I-insulin. Insulin and the new long acting insulin analog, glargine, interacted with the IGF-IR with over thousand and 100-fold less potency than IGF-I itself, whereas IGF-II had 6 times lower potency than IGF-I. Phosphorylation of the IGF-IR beta-subunit was obtained by concentrations of 10(-10)-10(-8)M IGF-I, 10(-6)M of insulin, inconsistently by 10(-8)M insulin and not at all by 10(-10)-10(-9)M insulin. The IR beta-subunit was phosphorylated by insulin and IGF-I at concentrations of 10(-9)-10(-8)M. When immunoprecipitating with specific monoclonal anti-IR or anti-IGF-IR alpha-subunit antibodies we found bands situated in slightly different positions suggesting the presence of Hybrid IR/IGF-IR. IGF-I, IGF-II and insulin (10(-9)-10(-7)M) had no significant effect on (3)H-thymidine incorporation into DNA. CONCLUSIONS: Human coronary endothelial cells express more IGF-IR than IR, mainly IR-A, and also Hybrid IR/IGF-IR. Both IGF-I and insulin phosphorylate their receptors, but only IGF-I seems to phosphorylate Hybrid IR/IGF-IR. Our study provides experimental evidence for a possible role of IGF-IR, IR and Hybrid IR/IGF-IR in human coronary artery endothelial cells.
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