Glucagon-like peptide 1 (GLP-1) metabolism was studied in halothane-anesthetized pigs (n = 7) using processing-independent (PI) and COOH-terminal (C) radioimmunoassays (RIA) and an enzyme-linked immunosorbent assay (ELISA) specific for biologically active GLP-1. Renal extraction of endogenous GLP-1 was detected by PI-RIA (33.1 +/- 13.3%) and C-RIA (16.0 +/- 6.3%) and by all assays during GLP-1 infusion (ELISA, 69.4 +/- 6.3%; PI-RIA, 32.6 +/- 7.3%; C-RIA, 43.7 +/- 3.4%), indicating substantial fragmentation. Hepatic and pulmonary degradation were undetectable under basal conditions, but exogenous GLP-1 elimination by the liver (43.6 +/- 8.9%) and lungs (10.1 +/- 3.2%) was measured by ELISA, suggesting primarily NH2-terminal degradation. Endogenous GLP-1 extraction by the hindleg was only detected by C-RIA (16.0 +/- 6.3%). During GLP-1 infusion, greater hindleg extraction was measured by ELISA (38.5 +/- 6.8%) and C-RIA (33.0 +/- 6.4%) than by PI-RIA (11.4 +/- 3.2%), indicating limited degradation at each terminus or more substantial COOH-terminal degradation. A shorter (P < 0.01) plasma half-life was revealed by ELISA (1.5 +/- 0.4 min) than by PI-RIA (4.5 +/- 0.6 min) or C-RIA (4.1 +/- 0.5 min). Metabolic clearance rates measured by PI-RIA (20.0 +/- 3.8 ml.min-1.kg-1) and C-RIA (15.5 +/- 1.6 ml.min-1.kg-1) were shorter (P < 0.01) than that measured by ELISA (106.8 +/- 14.7 ml.min-1.kg-1). Tissue-specific differential metabolism of GLP-1 occurs, and NH2-terminal degradation, rendering GLP-1 inactive, is particularly important in its clearance.
Glucose-dependent insulinotropic peptide (GIP) is known to be degraded by dipeptidyl peptidase IV (DPP IV), forming an inactive metabolite, but the extent of the enzyme's role in regulating the biological activity of GIP in vivo is still largely unknown. In nonfasted anesthetized pigs given an intravenous infusion of GIP, the intact peptide (determined by a novel NH 2 -terminally directed radioimmunoassay) accounts for only 14.5 ؎ 2.5% of total immunoreactivity. This is increased (to 40.9 ؎ 0.9%, P < 0.0001) by coadministration of valinepyrrolidide (a specific DPP IV inhibitor) at a dose that completely inhibits plasma DPP IV activity. The plasma t 1/2 of intact GIP is prolonged by the inhibitor (from 3.3 ؎ 0.3 to 8.1 ؎ 0.6 min; P < 0.001), whereas the t 1/2 for COOH-terminal immunoreactivity is unaffected (13.2 ؎ 0.5 and 11.5 ؎ 0.8 min, pre-and postinhibitor). Measurement of arteriovenous concentration differences revealed that the liver, kidney, and extremities are the main sites of removal of exogenous intact GIP (organ extractions, 28.0 ؎ 2.2, 26.3 ؎ 5.7, and 21.8 ؎ 3.0%, respectively). These organ extractions are reduced (P < 0.02) but not eliminated (kidney and extremities) by valine-pyrrolidide (to 6.5 ؎ 4.6, 14.1 ؎ 3.1, and 13.9 ؎ 2.4%, respectively). Valine-pyrrolidide potentiates the insulinotropic effect of GIP (P < 0.02), resulting in an enhanced glucose disappearance rate (k, from 8.0 ؎ 0.5 to 15.5 ؎ 2.2%/min; P < 0.01) and a reduction in the glucose excursion after an intravenous glucose load (area under the curve, from 133 ؎ 23 to 75 ؎ 9 min ⅐ mmol/l; P < 0.05). These results suggest that DPP IV plays an important role in GIP metabolism but is not the sole enzyme responsible for its NH 2 -terminal degradation. Nevertheless, DPP IV inhibition increases the proportion of intact peptide sufficiently to enhance its insulinotropic and antihyperglycemic effects. Diabetes 50:1588 -1597, 2001
Although symptoms worsened in patients with IBS at the onset of treatment with 20 g fructooligosaccharides/d, continuous treatment for 12 wk resulted in no worsening of symptoms.
Aim and objectives To review the literature on Nordic women's lived experiences and quality of life (QoL) after gynaecological cancer treatment. Background While incidence and survival are increasing in all groups of gynaecological cancers in the Nordic countries, inpatient hospitalisation has become shorter in relation to treatment. This has increased the need for follow‐up and rehabilitation. Design Integrative literature review using the Equator PRISMA guidelines. Methods The review was selected, allowing inclusion of both experimental and nonexperimental research. The search included peer‐reviewed articles published 1995–2017. To frame the search strategy, we applied the concept of rehabilitation, which holds a holistic perspective on health. Results Fifty‐five articles were included and were contextualised within three themes. Physical well-being in a changed body encompasses bodily changes comprising menopausal symptoms, a changed sexual life, complications in bowels, urinary tract, lymphoedema and pain, bodily‐based preparedness and fear of recurrence. Mental well-being as a woman deals with questioned womanliness, the experience of revitalised values in life, and challenges of how to come to terms with oneself after cancer treatment. Psychosocial well-being and interaction deals with the importance of having a partner or close person in the process of coming to terms with oneself after cancer. Furthermore, the women needed conversations with health professionals around the process of coping with changes and late effects, including intimate and sensitive issues. Conclusion Years after gynaecological cancer, women have to deal with fundamental changes and challenges concerning their physical, mental and psychosocial well‐being. Future research should focus on how follow‐up programmes can be organised to target the multidimensional aspects of women's QoL. Research collaboration across Nordic countries on rehabilitation needs and intervention is timely and welcomed. Relevance to clinical practice To ensure that all aspects of cancer rehabilitation are being addressed, we suggest that the individual woman is offered an active role in her follow‐up.
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