| 1. |
- Fanni, Giovanni, et al.
(författare)
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Effects of gastric bypass surgery on brain connectivity responses to hypoglycemia
- 2023
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Ingår i: Endocrine. - : Springer Nature. - 1355-008X .- 1559-0100 .- 0969-711X. ; 79:2, s. 304-312
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionRoux-en-Y gastric bypass (RYGB) leads to beneficial effects on glucose homeostasis, and attenuated hormonal counterregulatory responses to hypoglycemia are likely to contribute. RYGB also induces alterations in neural activity of cortical and subcortical brain regions. We aimed to characterize RYGB-induced changes in resting-state connectivity of specific brain regions of interest for energy homeostasis and behavioral control during hypoglycemia.MethodTen patients with BMI > 35 kg/m2 were investigated with brain PET/MR imaging during a hyperinsulinemic normo- and hypoglycemic clamp, before and 4 months after RYGB. Hormonal levels were assessed throughout the clamp. Resting-state (RS) fMRI scans were acquired in the glucose-lowering phase of the clamp, and they were analyzed with a seed-to-voxel approach.ResultsRS connectivity during initiation of hypoglycemia was significantly altered after RYGB between nucleus accumbens, thalamus, caudate, hypothalamus and their crosstalk with cortical and subcortical regions. Connectivity between the nucleus accumbens and the frontal pole was increased after RYGB, and this was associated with a reduction of ACTH (r = −0.639, p = 0.047) and cortisol (r = −0.635, p = 0.048) responses. Instead, connectivity between the caudate and the frontal pole after RYGB was reduced and this was associated with less attenuation of glucagon response during the hypoglycemic clamp (r = −0.728, p = 0.017), smaller reduction in fasting glucose (r = −0.798, p = 0.007) and less excess weight loss (r = 0.753, p = 0.012). No other significant associations were found between post-RYGB changes in ROI-to-voxel regional connectivity hormonal responses and metabolic or anthropometric outcomes.ConclusionRYGB alters brain connectivity during hypoglycemia of several neural pathways involved in reward, inhibitory control, and energy homeostasis. These changes are associated with altered hormonal responses to hypoglycemia and may be involved in the glucometabolic outcome of RYGB.
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| 2. |
- Hellman, Bo, et al.
(författare)
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Effects of external ATP on Ca(2+) signalling in endothelial cells isolated from mouse islets
- 2007
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 0969-711X .- 1559-0100. ; 32:1, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- External ATP is believed to initiate and propagate Ca2+ signals co-ordinating the insulin release pulses within and among the different islets in the pancreas. The possibility that islet endothelial cells participate in this process was evaluated by comparing the effects on [Ca2+]i of purinoceptor activation in these cells with those in β-cells. β-Cell-rich pancreatic islets were isolated from ob/ob mice and dispersed into single cells/aggregates. After culture with or without endothelial cell growth supplement (ECGS), the cytoplasmic Ca2+ concentration ([Ca2+]i) was measured with ratiometric fura-2 technique. Presence of ECGS or prolongation of culture (>5 days) resulted in proliferation of endothelial cells and altered their phenotype from rounded to elongated. Endothelial cells, preliminarily identified by attachment of Dynabeads coated with the Bandeiraea simplicifolia 1 lectin (BS-1), responded in a similar way as those stained with CD31 antibodies after measurements of [Ca2+]i. Spontaneous transients and oscillations of [Ca2+]i were seen in β-cells, but not in endothelial cells exposed to 20 mM glucose. Addition of ATP (10 μM) resulted in pronounced and more extended rise of [Ca2+]i in endothelial cells than in β-cells. The endothelial cells differed from the β-cells by also responding with a rise of [Ca2+]i to 10 μM UTP, but not to equimolar ADP and acetylcholine. The results support the idea of mutual interactions between islet endothelium and β-cells based on ATP-induced Ca2+ signals. It is suggested that the endothelial cells have a tonic inhibitory action on β-cell P2 purinoceptors resulting in impaired synchronization of the insulin release pulses.
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| 3. |
- Movérare-Skrtic, Sofia, et al.
(författare)
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Peripheral blood leukocyte distribution and body mass index are associated with the methylation pattern of the androgen receptor promoter.
- 2009
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 0969-711X .- 1355-008X .- 1559-0100. ; 35:2, s. 204-210
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Tidskriftsartikel (refereegranskat)abstract
- Methylation of CpG sites in the promoter region can affect gene transcription. DNA derived from peripheral blood leukocytes (PBL) from the well-characterized clinical cohorts might be useful to study the influence of environmental factors on DNA methylation. However, these studies could be confounded by the heterogeneous nature of PBL. The aims of this study were to determine the impact of PBL distribution on methylation status of the androgen receptor (AR) promoter, and determine the associations between PBL distribution-adjusted methylation status of the AR promoter and AR-related phenotypes. PBL differential count analyses were performed at the time of blood sampling for DNA preparation in 170 elderly men. The DNA was bisulfite treated, and the methylation status of five CpG units in the AR promoter was analyzed using a high-throughput technique based on MALDI-TOF mass spectrometry. The degree of methylation of all the five investigated CpG units was strongly positively associated with the percent of lymphocytes in the PBL (r (s) = 0.17-0.49, P < 0.05). Furthermore, the PBL distribution-adjusted methylation status of a specific CpG unit in the AR promoter was significantly associated with body mass index (r (s) = 0.24) and other measures reflecting fat mass in elderly men. In conclusion, adjustment for PBL distribution needs to be done to be able to use DNA from whole blood for methylation analysis of the AR promoter and most likely also when investigating other promoters.
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| 4. |
- Sjögren, Klara, 1970, et al.
(författare)
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A model for tissue-specific inducible insulin-like growth factor-I (IGF-I) inactivation to determine the physiological role of liver-derived IGF-I.
- 2002
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Ingår i: Endocrine. - 0969-711X. ; 19:3, s. 249-56
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor-I (IGF-I) has important growthpromoting and metabolic effects and is expressed in virtually every tissue of the body. The highest expression is found in the liver, but the physiological role of liver-derived IGF-I is unknown. It has been difficult to separate the endocrine effects of liver-derived IGF-I from the autocrine/paracrine effects of locally produced IGF-I in peripheral tissues. Therefore, we have developed a mouse model with a liver-specific inducible deletion of the IGF-I gene (LI-IGF-I-/- mouse). The LI-IGF-I-/- mouse has dramatically reduced (>80%) serum IGF-I levels, demonstrating that the major part of serum IGF-I is liver-derived. Surprisingly, LI-IGFI -/- mice demonstrate a normal appendicular skeletal growth up to at least 12 mo of age despite the dramatic decrease in circulating IGF-I levels, indicating that liver-derived IGF-I is not required for appendicular skeletal growth. However, the adult axial skeletal growth is reduced in the LI-IGF-I-/- mice. Furthermore, the amount of cortical bone is reduced due to decreased radial growth of the cortical bone, while the trabecular bone mineral density is unchanged in the LI-IGFI -/- mice. The decreased levels of circulating IGF-I are associated with increased serum levels of growth hormone (GH), indicating a role for liver-derived IGFI in the negative-feedback regulation of GH secretion. Measurements of factors regulating GH secretion in the pituitary and in the hypothalamus revealed an increased expression of GH-releasing-hormone (GHRH) and GHsecretagogue (GHS) receptors in the pituitary of LI-IGFI -/- mice. This in turn results in an increased sensitivity to systemically administered GHRH and GHS, demonstrating that the regulatory action of liver-derived IGF-I on GH secretion is at the pituitary rather than at the hypothalamic level. The liver is an important metabolic organ and LI-IGF-I-/- mice are markedly hyperinsulinemic and yet normoglycemic, consistent with an adequately compensated insulin resistance. Interestingly, LI-IGF-I-/- mice display a reduced age-dependent fat mass accumulation compared with control mice. Furthermore, LI-IGF-I-/- mice have increased blood pressure attributable to increased peripheral resistance indicating a role for liver-derived IGF-I in the regulation of blood pressure. In conclusion, liver-derived IGF-I is important for carbohydrate and lipid metabolism and for the regulation of GH secretion at the pituitary level. Furthermore, it regulates adult axial skeletal growth and cortical radial growth while it is not required for appendicular skeletal growth.
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| 5. |
- Starker, Lee F., et al.
(författare)
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Expression and somatic mutations of SDHAF2 (SDH5), a novel endocrine tumor suppressor gene in parathyroid tumors of primary hyperparathyroidism
- 2010
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 0969-711X .- 1355-008X .- 1559-0100. ; 38:3, s. 397-401
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the SDHAF2 gene and its effect on primary hyperparathyroidism. Parathyroid tumors causing primary hyperparathyroidism (pHPT) are one of the more common endocrine neoplasias. Loss of heterozygosity at chromosome 11q13 is the most common chromosomal aberration in parathyroid tumors occurring in about 40% of sporadic tumors. Only 15-19% display somatic mutations in the MEN1 gene, which suggest that this chromosomal region may harbor additional genes of importance in parathyroid tumor development. The SDHAF2 (formerly SDH5) gene is a recently identified neuroendocrine tumor suppressor gene at this locus, and inherited mutations of the SDHAF2 gene has been linked to familial paraganglioma. We demonstrate that the SDHAF2 gene is expressed in parathyroid tissue using RT-PCR. Because detection of inactivating mutations is the major criterion for validating a candidate tumor suppressor, we used automated sequencing of the coding region and intron/exon boundaries in 80 sporadic parathyroid adenomas from patients with pHPT. A known polymorphisms (A to G substitution; rs879647) was identified in 9/80 parathyroid tumors but no tumor-specific somatic mutational aberrations, such as nonsense, frameshift, or other inactivating mutations were identified. The SDHAF2 gene is expressed in parathyroid tissue. However, somatic mutations of the SDHAF2 tumor suppressor gene are unlikely to frequently contribute to parathyroid tumor development in sporadic pHPT.
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| 6. |
- Svensson, Johan, 1964, et al.
(författare)
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Effects of growth hormone and its secretagogues on bone.
- 2001
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Ingår i: Endocrine. - 0969-711X. ; 14:1, s. 63-6
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Tidskriftsartikel (refereegranskat)abstract
- The growth hormone (GH)/insulin-like growth factor-1 axis is not only of importance for linear body growth during childhood, but it is also one of the major determinants of adult bone mass. Studies show that GH treatment increases bone mass in rodents as well as in adult GH-deficient humans, but the effect of GH treatment on bone mass in healthy humans has so far not been impressive. Recently, a new class of GH secretagogues (GHSs) has been developed. In humans, GHS treatment affects biochemical markers of bone turnover and increases growth velocity in selected short children with or without GH deficiency. In rodents, GHS treatment increase bone mineral content, but it has not yet been shown that GHS treatment can affect bone mass in adult humans.
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