Skeletal muscle is a heterogeneous tissue composed of different fiber types. Studies suggest that insulinmediated glucose metabolism is different between muscle fiber types. We hypothesized that differences are due to fiber type-specific expression/regulation of insulin signaling elements and/or metabolic enzymes. Pools of type I and II fibers were prepared from biopsies of the vastus lateralis muscles from lean, obese, and type 2 diabetic subjects before and after a hyperinsulinemiceuglycemic clamp. Type I fibers compared with type II fibers have higher protein levels of the insulin receptor, GLUT4, hexokinase II, glycogen synthase (GS), and pyruvate dehydrogenase-E1a (PDH-E1a) and a lower protein content of Akt2, TBC1 domain family member 4 (TBC1D4), and TBC1D1. In type I fibers compared with type II fibers, the phosphorylation response to insulin was similar (TBC1D4, TBC1D1, and GS) or decreased (Akt and PDH-E1a). Phosphorylation responses to insulin adjusted for protein level were not different between fiber types. Independently of fiber type, insulin signaling was similar (TBC1D1, GS, and PDH-E1a) or decreased (Akt and TBC1D4) in muscle from patients with type 2 diabetes compared with lean and obese subjects. We conclude that human type I muscle fibers compared with type II fibers have a higher glucose-handling capacity but a similar sensitivity for phosphoregulation by insulin.Skeletal muscle is important for whole-body insulinstimulated glucose disposal (1), and skeletal muscle insulin resistance is a common phenotype of obesity and type 2 diabetes (T2D) (2). Skeletal muscle is a heterogeneous tissue composed of different fiber types, which can be divided according to myosin heavy chain (MHC) isoform expression. Studies in rodents show that insulin-stimulated glucose uptake in the oxidative type I fiber-dominant muscles is higher than in muscles with a high degree of glycolytic type II fibers (3-6). Whether this phenomenon is due to differences in locomotor activity of individual muscles or a direct consequence of the fiber-type composition is largely unknown. In incubated rat muscle, insulin-induced glucose uptake was higher (;100%) in type IIa (oxidative/glycolytic) compared with IIx and IIb (glycolytic) fibers (7,8), suggesting that insulin-mediated glucose uptake is related to the oxidative capacity of the muscle fiber. In humans, a positive correlation between proportions of type I fibers in muscle and whole-body insulin sensitivity has been demonstrated (9-11). Furthermore, insulin-stimulated glucose transport in human muscle strips was associated with the relative type I fiber content (12). Thus, it is likely that human type I fibers are more important than type II fibers for maintaining glucose homeostasis in response to insulin. Indeed, a decreased proportion of type I fibers has been found in various insulin resistant states such as the metabolic syndrome (9), obesity (13,14), T2D in some (10,13,14) but not all (12,15) studies and following bedrest (16), as well as in tetraplegic patients (17), ...
BackgroundResearch has illustrated that the decision-making process regarding healthcare seeking for symptoms is complex and associated with a variety of factors, including gender differences. Enhanced understanding of the frequency of symptoms and the healthcare seeking behaviour in the general population may increase our knowledge of this complex field.The primary objective of this study was to estimate the prevalence of self-reported symptoms and the proportion of individuals reporting GP contact, in a large Danish nationwide cohort. A secondary objective was to explore gender differences in GP contacts in response to experiencing one of the 44 predefined symptoms.MethodsA Danish nationwide cohort study including a random sample of 100,000 individuals, representative of the adult Danish population aged 20 years or above. A web-based questionnaire survey formed the basis of this study. A total of 44 different symptoms covering a wide area of alarm symptoms and non-specific frequently occurring symptoms were selected based on extensive literature search. Further, items regarding contact to the GP were included. Data on socioeconomic factors were obtained from Statistics Denmark.ResultsA total of 49,706 subjects completed the questionnaire. Prevalence estimates of symptoms varied from 49.4 % (24,537) reporting tiredness to 0.11 % (54) reporting blood in vomit. The mean number of reported symptoms was 5.4 (men 4.8; women 6.0).The proportion of contact to the GP with at least one symptom was 37 %. The largest proportion of GP contacts was seen for individuals reporting blood in the urine (73.2 %), whereas only 11.4 % of individuals with increase in waist circumference reported GP contact. For almost 2/3 of the symptoms reported, no gender differences were found concerning the proportion leading to GP contacts.ConclusionPrevalence of symptoms and GP contacts are common in this overview of 44 different self-reported symptoms. For almost 2/3 of the reported symptoms no gender differences were found concerning the proportion leading to GP contacts. An enhanced understanding of healthcare seeking decisions may assist healthcare professionals in identifying patients who are at risk of postponing contact to the GP and may help development of health campaigns targeting these individuals.
BackgroundDifferences in cancer awareness between individuals may explain variations in healthcare seeking behaviour and ultimately also variations in cancer survival. It is therefore important to examine cancer awareness and to investigate possible differences in cancer awareness among specific population subgroups. The aim of this study is to assess awareness of cancer symptoms, risk factors and perceived 5-year survival from bowel, breast, ovarian, and lung cancer in a Danish population sample and to analyse the association between these factors and socio-economic position indicators.MethodsA population-based telephone survey was carried out among 1,000 respondents aged 30–49 years and 2,000 respondents aged 50 years and older using the Awareness and Beliefs about Cancer measure. Information on socio-economic position was obtained by data linkage through Statistics Denmark. Prevalence ratios were used to determine the association between socio-economic position and cancer awareness.ResultsA strong socio-economic gradient in cancer awareness was found. People with a low educational level and a low household income were more likely to have a lower awareness of cancer symptoms, cancer risk factors and the growing risk of cancer with age. Furthermore, men and people outside the labour force tended to be less aware of these factors than women and people within the labour force. However, women were more likely than men to lack awareness of the relationship between age and cancer risk. No clear associations were found between socio-economic position and lack of awareness of 5-year survival from bowel, breast, ovarian, and lung cancers.ConclusionsAs cancer awareness has shown to be positively associated with cancer-related behaviour, e.g. healthcare seeking, consideration must be given to tackle inequalities in cancer awareness and to address this issue in future public health strategies, which should be targeted at and tailored to the intended recipient groups.
Current evidence on exercise-mediated AMPK regulation in skeletal muscle of patients with type 2 diabetes (T2D) is inconclusive. This may relate to inadequate segregation of trimeric complexes in the investigation of AMPK activity. We examined the regulation of AMPK and downstream targets ACC-b, TBC1D1, and TBC1D4 in muscle biopsy specimens obtained from 13 overweight/obese patients with T2D and 14 weight-matched male control subjects before, immediately after, and 3 h after exercise. ences in these responses were observed between patients with T2D and control subjects. Subjects were also studied by euglycemic-hyperinsulinemic clamps performed at rest and 3 h after exercise. We found no evidence for insulin to regulate AMPK activity. Thus, AMPK signaling is not compromised in muscle of patients with T2D during exercise and insulin stimulation. Our results reveal a hitherto unrecognized activation of specific AMPK complexes in exercise recovery. We hypothesize that the differential regulation of AMPK complexes plays an important role for muscle metabolism and adaptations to exercise.
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