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- Berryman, Darlene E, et al.
(författare)
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The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations.
- 2013
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Ingår i: Nature reviews. Endocrinology. - : Springer Science and Business Media LLC. - 1759-5037 .- 1759-5029. ; 9:6, s. 346-56
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Tidskriftsartikel (refereegranskat)abstract
- Obesity has become one of the most common medical problems in developed countries, and this disorder is associated with high incidences of hypertension, dyslipidaemia, cardiovascular disease, type 2 diabetes mellitus and specific cancers. Growth hormone (GH) stimulates the production of insulin-like growth factor 1 in most tissues, and together GH and insulin-like growth factor 1 exert powerful collective actions on fat, protein and glucose metabolism. Clinical trials assessing the effects of GH treatment in patients with obesity have shown consistent reductions in total adipose tissue mass, in particular abdominal and visceral adipose tissue depots. Moreover, studies in patients with abdominal obesity demonstrate a marked effect of GH therapy on body composition and on lipid and glucose homeostasis. Therefore, administration of recombinant human GH or activation of endogenous GH production has great potential to influence the onset and metabolic consequences of obesity. However, the clinical use of GH is not without controversy, given conflicting results regarding its effects on glucose metabolism. This Review provides an introduction to the role of GH in obesity and summarizes clinical and preclinical data that describe how GH can influence the obese state.
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| 4. |
- Delzenne, Nathalie, et al.
(författare)
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Targeting gut microbiota in obesity: effects of prebiotics and probiotics
- 2011
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Ingår i: Nature reviews. Endocrinology. - : Springer Science and Business Media LLC. - 1759-5029 .- 1759-5037. ; 7:11, s. 639-646
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Forskningsöversikt (refereegranskat)abstract
- At birth, the human colon is rapidly colonized by gut microbes. Owing to their vast number and their capacity to ferment nutrients and secrete bioactive compounds, these gastrointestinal microbes act as an environmental factor that affects the host's physiology and metabolism, particularly in the context of obesity and its related metabolic disorders. Experiments that compared germ-free and colonized mice or analyzed the influence of nutrients that qualitatively change the composition of the gut microbiota (namely prebiotics) showed that gut microbes induce a wide variety of host responses within the intestinal mucosa and thereby control the gut's barrier and endocrine functions. Gut microbes also influence the metabolism of cells in tissues outside of the intestines (in the liver and adipose tissue) and thereby modulate lipid and glucose homeostasis, as well as systemic inflammation, in the host. A number of studies describe characteristic differences between the composition and/or activity of the gut microbiota of lean individuals and those with obesity. Although these data are controversial, they suggest that specific phyla, classes or species of bacteria, or bacterial metabolic activities could be beneficial or detrimental to patients with obesity. The gut microbiota is, therefore, a potential nutritional and pharmacological target in the management of obesity and obesity-related disorders.
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| 7. |
- Lernmark, Åke, et al.
(författare)
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Immune therapy in type 1 diabetes mellitus.
- 2013
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Ingår i: Nature Reviews Endocrinology. - : Springer Science and Business Media LLC. - 1759-5037 .- 1759-5029. ; 9:2, s. 92-103
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Forskningsöversikt (refereegranskat)abstract
- Type 1 diabetes mellitus (T1DM) is an autoimmune disorder directed against the β cells of the pancreatic islets. The genetic risk of the disease is linked to HLA-DQ risk alleles and unknown environmental triggers. In most countries, only 10-15% of children or young adults newly diagnosed with T1DM have a first-degree relative with the disease. Autoantibodies against insulin, GAD65, IA-2 or the ZnT8 transporter mark islet autoimmunity. These islet autoantibodies may already have developed in children of 1-3 years of age. Immune therapy in T1DM is approached at three different stages. Primary prevention is treatment of individuals at increased genetic risk. For example, one trial is testing if hydrolyzed casein milk formula reduces T1DM incidence in genetically predisposed infants. Secondary prevention is targeted at individuals with persistent islet autoantibodies. Ongoing trials involve nonautoantigen-specific therapies, such as Bacillus Calmette-Guérin vaccine or anti-CD3 monoclonal antibodies, or autoantigen-specific therapies, including oral and nasal insulin or alum-formulated recombinant human GAD65. Trial interventions at onset of T1DM have also included nonautoantigen-specific approaches, and autoantigen-specific therapies, such as proinsulin peptides. Although long-term preservation of β-cell function has been difficult to achieve in many studies, considerable progress is being made through controlled clinical trials and animal investigations towards uncovering mechanisms of β-cell destruction. Novel therapies that prevent islet autoimmunity or halt progressive β-cell destruction are needed.
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| 8. |
- Lidell, Martin, 1970, et al.
(författare)
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Brown adipose tissue-a new role in humans?
- 2010
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Ingår i: Nature reviews. Endocrinology. - : Springer Science and Business Media LLC. - 1759-5037 .- 1759-5029. ; 6, s. 319-325
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Forskningsöversikt (refereegranskat)abstract
- New targets for pharmacological interventions are of great importance to combat the epidemic of obesity. Brown adipose tissue could potentially represent one such target. Unlike white adipose tissue, brown adipose tissue has the ability to dissipate energy by producing heat rather than storing it as triglycerides. In small mammals, the presence of active brown adipose tissue is pivotal for the maintenance of body temperature and possibly to protect against the detrimental effects of surplus energy intake. Animal studies have shown that expansion and/or activation of brown adipose tissue counteracts diet-induced weight gain and related disorders such as type 2 diabetes mellitus. Several independent studies have now confirmed the presence of functional brown adipose tissue in adult humans, for whom this tissue is probably metabolically beneficial given its association with both low BMI and low total adipose tissue content. Over the past few years, knowledge of the transcriptional control and development of brown adipose tissue has increased substantially. Thus, several possible targets that may be useful for the expansion and/or activation of this tissue by pharmacological means have been identified. Whether or not brown adipose tissue will be useful in the battle against obesity remains to be seen. However, this possibility is certainly well worth exploring.
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| 10. |
- Nyberg, Fred, 1945-, et al.
(författare)
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Growth hormone and cognitive function
- 2013
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Ingår i: Nature reviews. Endocrinology. - : Springer Science and Business Media LLC. - 1759-5029 .- 1759-5037. ; 9:6, s. 357-365
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Forskningsöversikt (refereegranskat)abstract
- Emerging data indicate that growth hormone (GH) therapy could have a role in improving cognitive function. GH replacement therapy in experimental animals and human patients counteracts the dysfunction of many behaviours related to the central nervous system (CNS). Various behaviours, such as cognitive behaviours related to learning and memory, are known to be induced by GH; the hormone might interact with specific receptors located in areas of the CNS that are associated with the functional anatomy of these behaviours. GH is believed to affect excitatory circuits involved in synaptic plasticity, which alters cognitive capacity. GH also has a protective effect on the CNS, as indicated by its beneficial effects in patients with spinal cord injury. Data collected from animal models indicates that GH might also stimulate neurogenesis. This Review discusses the mechanisms underlying the interactions between GH and the CNS, and the data emerging from animal and human studies on the relationship between GH and cognitive function. In this article, particular emphasis is given to the role of GH as a treatment for patients with cognitive impairment resulting from deficiency of the hormone.
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