SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "L773:0012 1797 OR L773:1939 327X srt2:(2015-2019)"

Sökning: L773:0012 1797 OR L773:1939 327X > (2015-2019)

Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Abrahamsson, Niclas, et al. (författare)
  • Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia
  • 2016
  • Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 65:9, s. 2667-2675
  • Tidskriftsartikel (refereegranskat)abstract
    • Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.
  •  
2.
  • Abrahamsson, Niclas, 1976-, et al. (författare)
  • Gastric bypass reduces symptoms and hormonal responses to hypoglycemia
  • 2016
  • Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 65:9, s. 2667-2675
  • Tidskriftsartikel (refereegranskat)abstract
    • Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.
  •  
3.
  • Alenkvist, Ida, et al. (författare)
  • Recruitment of Epac2A to Insulin Granule Docking Sites Regulates Priming for Exocytosis
  • 2017
  • Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 66:10, s. 2610-2622
  • Tidskriftsartikel (refereegranskat)abstract
    • Epac is a cAMP-activated guanine nucleotide exchange factor that mediates cAMP signaling in various types of cells, including -cells, where it is involved in the control of insulin secretion. Upon activation, the protein redistributes to the plasma membrane, but the underlying molecular mechanisms and functional consequences are unclear. Using quantitative high-resolution microscopy, we found that cAMP elevation caused rapid binding of Epac2A to the -cell plasma membrane, where it accumulated specifically at secretory granules and rendered them more prone to undergo exocytosis. cAMP-dependent membrane binding required the high-affinity cyclic nucleotide-binding (CNB) and Ras association domains, but not the disheveled-Egl-10-pleckstrin domain. Although the N-terminal low-affinity CNB domain (CNB-A) was dispensable for the translocation to the membrane, it was critical for directing Epac2A to the granule sites. Epac1, which lacks the CNB-A domain, was recruited to the plasma membrane but did not accumulate at granules. We conclude that Epac2A controls secretory granule release by binding to the exocytosis machinery, an effect that is enhanced by prior cAMP-dependent accumulation of the protein at the plasma membrane.
  •  
4.
  • Aydemir, Özkan, et al. (författare)
  • Genetic Variation Within the HLA-DRA1 Gene Modulates Susceptibility to Type 1 Diabetes in HLA-DR3 Homozygotes
  • 2019
  • Ingår i: Diabetes. - : American Diabetes Association Inc.. - 1939-327X .- 0012-1797. ; 68:7, s. 1523-1527
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 1 diabetes (T1D) involves the interaction of multiple gene variants, environmental factors, and immunoregulatory dysfunction. Major T1D genetic risk loci encode HLA-DR and -DQ. Genetic heterogeneity and linkage disequilibrium in the highly polymorphic HLA region confound attempts to identify additional T1D susceptibility loci. To minimize HLA heterogeneity, T1D patients (N = 365) and control subjects (N = 668) homozygous for the HLA-DR3 high-risk haplotype were selected from multiple large T1D studies and examined to identify new T1D susceptibility loci using molecular inversion probe sequencing technology. We report that risk for T1D in HLA-DR3 homozygotes is increased significantly by a previously unreported haplotype of three single nucleotide polymorphisms (SNPs) within the first intron of HLA-DRA1. The homozygous risk haplotype has an odds ratio of 4.65 relative to the protective homozygous haplotype in our sample. Individually, these SNPs reportedly function as "expression quantitative trait loci," modulating HLA-DR and -DQ expression. From our analysis of available data, we conclude that the tri-SNP haplotype within HLA-DRA1 may modulate class II expression, suggesting that increased T1D risk could be attributable to regulated expression of class II genes. These findings could help clarify the role of HLA in T1D susceptibility and improve diabetes risk assessment, particularly in high-risk HLA-DR3 homozygous individuals.
  •  
5.
  • Barbarroja, Nuria, et al. (författare)
  • Increased dihydroceramide/ceramide ratio mediated by defective expression of degs1 impairs adipocyte differentiation and function
  • 2015
  • Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 64:4, s. 1180-1192
  • Tidskriftsartikel (refereegranskat)abstract
    • Adipose tissue dysfunction is an important determinant of obesity-associated, lipid-induced metabolic complications. Ceramides are well-known mediators of lipid-induced insulin resistance in peripheral organs such as muscle. DEGS1 is the desaturase catalyzing the last step in the main ceramide biosynthetic pathway. Functional suppression of DEGS1 activity results in substantial changes in ceramide species likely to affect fundamental biological functions such as oxidative stress, cell survival, and proliferation. Here, we show that degs1 expression is specifically decreased in the adipose tissue of obese patients and murine models of genetic and nutritional obesity. Moreover, loss-of-function experiments using pharmacological or genetic ablation of DEGS1 in preadipocytes prevented adipogenesis and decreased lipid accumulation. This was associated with elevated oxidative stress, cellular death, and blockage of the cell cycle. These effects were coupled with increased dihydroceramide content. Finally, we validated in vivo that pharmacological inhibition of DEGS1 impairs adipocyte differentiation. These data identify DEGS1 as a new potential target to restore adipose tissue function and prevent obesity-associated metabolic disturbances.
  •  
6.
  •  
7.
  • Carlbom, Lina, et al. (författare)
  • [(11)C]5-Hydroxy-Tryptophan PET for Assessment of Islet Mass During Progression of Type 2 Diabetes
  • 2017
  • Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 66:5, s. 1286-1292
  • Tidskriftsartikel (refereegranskat)abstract
    • [(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP) PET of the pancreas has been shown to be a surrogate imaging biomarker of pancreatic islet mass. The change in islet mass in different stages of type 2 diabetes (T2D) as measured by non-invasive imaging is currently unknown. Here, we describe a cross-sectional study where subjects at different stages of T2D development with expected stratification of pancreatic islet mass were examined in relation to non-diabetic individuals. The primary outcome was the [(11)C]5-HTP uptake and retention in pancreas, as a surrogate marker for the endogenous islet mass.We found that metabolic testing indicated a progressive loss of beta cell function, but that this was not mirrored by a decrease in [(11)C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased beta cell function. The results herein indicates that beta cell dedifferentiation, and not necessarily endocrine cell loss, constitute a major cause of beta cell failure in T2D.
  •  
8.
  •  
9.
  • Carlsson, Per-Ola, et al. (författare)
  • Preserved Beta-Cell Function in Type 1 Diabetes by Mesenchymal Stromal Cells
  • 2015
  • Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 64:2, s. 587-592
  • Tidskriftsartikel (refereegranskat)abstract
    • The retention of endogenous insulin secretion in type 1 diabetes is an attractive clinical goal, which opens possibilities for long-term restoration of glucose metabolism. Mesenchymal stromal cells (MSCs) constitute, based on animal studies, a promising interventional strategy for the disease. This prospective clinical study describes the translation of this cellular intervention strategy to patients with recent onset type 1 diabetes. Twenty adult patients with newly diagnosed type 1 diabetes were enrolled and randomized to MSC treatment or to the control group. Residual beta-cell function was analyzed as C-peptide concentrations in blood in response to a mixed meal tolerance test (MMTT) at one-year follow-up. In contrast to the patients in the control arm, who showed loss in both C-peptide peak values and C-peptide when calculated as area under the curve during the first year, these responses were preserved or even increased in the MSC-treated patients. Importantly, no side effects of MSC treatment were observed. We conclude that autologous MSC treatment in new onset type 1 diabetes constitute a safe and promising strategy to intervene in disease progression and preserve beta-cell function.
  •  
10.
  • Cedernaes, Jonathan, et al. (författare)
  • Determinants of Shortened, Disrupted, and Mistimed Sleep and Associated Metabolic Health Consequences in Healthy Humans
  • 2015
  • Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 64:4, s. 1073-1080
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent increases in the prevalence of obesity and type 2 diabetes mellitus (T2DM) in modern societies have been paralleled by reductions in the time their denizens spend asleep. Epidemiological studies have shown that disturbed sleepcomprising short, low-quality, and mistimed sleepincreases the risk of metabolic diseases, especially obesity and T2DM. Supporting a causal role of disturbed sleep, experimental animal and human studies have found that sleep loss can impair metabolic control and body weight regulation. Possible mechanisms for the observed changes comprise sleep loss-induced changes in appetite-signaling hormones (e.g., higher levels of the hunger-promoting hormone ghrelin) or hedonic brain responses, altered responses of peripheral tissues to metabolic signals, and changes in energy intake and expenditure. Even though the overall consensus is that sleep loss leads to metabolic perturbations promoting the development of obesity and T2DM, experimental evidence supporting the validity of this view has been inconsistent. This Perspective aims at discussing molecular to behavioral factors through which short, low-quality, and mistimed sleep may threaten metabolic public health. In this context, possible factors that may determine the extent to which poor sleep patterns increase the risk of metabolic pathologies within and across generations will be discussed (e.g., timing and genetics).
  •  
Skapa referenser, mejla, bekava och länka
Typ av publikation
tidskriftsartikel (114)
konferensbidrag (4)
forskningsöversikt (2)
Typ av innehåll
refereegranskat (109)
övrigt vetenskapligt (11)
Författare/redaktör
Korsgren, Olle (12)
Groop, Leif (12)
Lernmark, Åke (12)
Franks, Paul W (9)
Zierath, JR (7)
Wareham, Nicholas J (7)
visa fler...
Franks, Paul (6)
Lyssenko, Valeriya (6)
Langenberg, Claudia (6)
Scott, Robert A (6)
Ingelsson, Erik (6)
She, Jin-Xiong (6)
Toppari, Jorma (6)
Akolkar, Beena (6)
Ahlqvist, Emma (5)
Lind, Lars (5)
Nilsson, Peter (5)
McCarthy, Mark I (5)
Ladenvall, Claes (5)
Pedersen, Oluf (5)
Hansen, Torben (5)
Ingelsson, E (5)
Ludvigsson, Johnny (5)
Smith, Ulf, 1943 (5)
Ziegler, Anette-G (5)
Dupuis, Josée (5)
van der Schouw, Yvon ... (5)
Korsgren, O. (4)
Krook, A (4)
Tuomi, Tiinamaija (4)
Melander, Olle (4)
Lind, L (4)
Lee, Hye-Seung (4)
Carlsson, Annelie (4)
Ling, Charlotte (4)
Sala, Núria (4)
Stancáková, Alena (4)
Eriksson, Olof (4)
Grarup, Niels (4)
Hansen, T (4)
Pedersen, O (4)
Grarup, N (4)
Knowler, William C. (4)
Geraghty, Daniel E (4)
Lernmark, Ake (4)
Törn, Carina (4)
Rewers, Marian (4)
Meigs, James B. (4)
Strawbridge, RJ (4)
Prokopenko, Inga (4)
visa färre...
Lärosäte
Lunds universitet (42)
Uppsala universitet (35)
Karolinska Institutet (34)
Göteborgs universitet (16)
Umeå universitet (9)
Linköpings universitet (4)
visa fler...
Stockholms universitet (2)
Örebro universitet (1)
visa färre...
Språk
Engelska (120)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (92)
Naturvetenskap (3)
Samhällsvetenskap (1)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy