| 1. |
- Carr, Richard D., et al.
(författare)
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Incretin and islet hormonal responses to fat and protein ingestion in healthy men
- 2008
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Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 295:4, s. 779-784
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) regulate islet function after carbohydrate ingestion. Whether incretin hormones are of importance for islet function after ingestion of noncarbohydrate macronutrients is not known. This study therefore examined integrated incretin and islet hormone responses to ingestion of pure fat (oleic acid; 0.88 g/kg) or protein (milk and egg protein; 2 g/kg) over 5 h in healthy men, aged 20-25 yr (n = 12); plain water ingestion served as control. Both intact (active) and total GLP-1 and GIP levels were determined as was plasma activity of dipeptidyl peptidase-4 (DPP-4). Following water ingestion, glucose, insulin, glucagon, GLP-1, and GIP levels and DPP-4 activity were stable during the 5-h study period. Both fat and protein ingestion increased insulin, glucagon, GIP, and GLP-1 levels without affecting glucose levels or DPP-4 activity. The GLP-1 responses were similar after protein and fat, whereas the early (30 min) GIP response was higher after protein than after fat ingestion (P < 0.001). This was associated with sevenfold higher insulin and glucagon responses compared with fat ingestion (both P < 0.001). After protein, the early GIP, but not GLP-1, responses correlated to insulin (r(2) = 0.86; P = 0.0001) but not glucagon responses. In contrast, after fat ingestion, GLP-1 and GIP did not correlate to islet hormones. We conclude that, whereas protein and fat release both incretin and islet hormones, the early GIP secretion after protein ingestion may be of primary importance to islet hormone secretion.
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| 2. |
- Carr, Richard D, et al.
(författare)
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Secretion and Dipeptidyl Peptidase-4-Mediated Metabolism of Incretin Hormones after a Mixed Meal or Glucose Ingestion in Obese Compared to Lean, Nondiabetic Men.
- 2010
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 872-878
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Tidskriftsartikel (refereegranskat)abstract
- Context: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are cleaved by dipeptidyl peptidase-4 (DPP-4); plasma activity of DPP-4 may be increased in obesity. The impact of this increase on incretin hormone secretion and metabolism is not known. Objective: The aim of the study was to assess incretin hormone secretion and degradation in lean and obese nondiabetic subjects. Design, Settings, and Participants: We studied the ingestion of a mixed meal (560 kcal) or oral glucose (2 g/kg) in healthy lean (n = 12; body mass index, 20-25 kg/m(2)) or obese (n = 13; body mass index, 30-35 kg/m(2)) males at a University Clinical Research Unit. Main Outcome Measures: We measured the area under the curve of plasma intact (i) and total (t) GIP and GLP-1 after meal ingestion and oral glucose. Results: Plasma DPP-4 activity was higher in the obese subjects (38.5 +/- 3.0 vs. 26.7 +/- 1.6 mmol/min . mul; P = 0.002). Although GIP secretion (AUCtGIP) was not reduced in obese subjects after meal ingestion or oral glucose, AUCiGIP was lower in obese subjects (8.5 +/- 0.6 vs. 12.7 +/- 0.9 nmol/liter x 300 min; P < 0.001) after meal ingestion. GLP-1 secretion (AUCtGLP-1) was reduced in obese subjects after both meal ingestion (7.3 +/- 0.9 vs. 10.0 +/- 0.6 nmol/liter x 300 min; P = 0.022) and oral glucose (6.6 +/- 0.8 vs. 9.6 +/- 1.1 nmol/liter x 180 min; P = 0.035). iGLP-1 was reduced in parallel to tGLP-1. Conclusions: 1) Release and degradation of the two incretin hormones show dissociated changes in obesity: GLP-1 but not GIP secretion is lower after meal ingestion and oral glucose, whereas GIP but not GLP-1 metabolism is increased after meal ingestion. 2) Increased plasma DPP-4 activity in obesity is not associated with a generalized augmented incretin hormone metabolism.
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| 3. |
- Gunnarsson, Thomas, et al.
(författare)
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Glucose-induced incretin hormone release and inactivation are differently modulated by oral fat and protein in mice.
- 2006
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 147:7, s. 3173-3180
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Tidskriftsartikel (refereegranskat)abstract
- Monounsaturated fatty acids, such as oleic acid (OA), and certain milk proteins, especially whey protein (WP), have insulinotropic effects and can reduce postprandial glycemia. This effect may involve the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). To explore this, we examined the release and inactivation of GIP and GLP-1 after administration of glucose with or without OA or WP through gastric gavage in anesthetized C57BL/6J mice. Insulin responses to glucose (75 mg) were 3-fold augmented by addition of WP (75 mg; P < 0.01), which was associated with enhanced oral glucose tolerance (P < 0.01). The insulin response to glucose was also augmented by addition of OA (34 mg; P < 0.05) although only 1.5-fold and with no associated increase in glucose elimination. The slope of the glucose-insulin curve was increased by OA (1.7-fold; P < 0.05) and by WP(4-fold; P < 0.01) compared with glucose alone, suggesting potentiation of glucose-stimulated insulin release. WP increased GLP-1 secretion (P < 0.01), whereas GIP secretion was unaffected. OA did not affect GIP or GLP-1 secretion. Nevertheless, WP increased the levels of both intact GIP and intact GLP-1 (both P < 0.01), and OA increased the levels of intact GLP-1 (P < 0.05). WP inhibited dipeptidyl peptidase IV activity in the proximal small intestine by 50% (P < 0.05), suggesting that luminal degradation of WP generates small fragments, which are substrates for dipeptidyl peptidase IV and act as competitive inhibitors. We therefore conclude that fat and protein may serve as exogenous regulators of secretion and inactivation of the incretin hormones with beneficial influences on glucose metabolism.
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| 4. |
- Kapun, Martin, et al.
(författare)
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Drosophila Evolution over Space and Time (DEST) : A New Population Genomics Resource
- 2021
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 38:12, s. 5782-5805
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Tidskriftsartikel (refereegranskat)abstract
- Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome data sets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate data sets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 previously published and unpublished population samples from over 100 locations in >20 countries on four continents. Several of these locations have been sampled at different seasons across multiple years. This data set, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental metadata. A web-based genome browser and web portal provide easy access to the SNP data set. We further provide guidelines on how to use Pool-Seq data for model-based demographic inference. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan data set. Our resource will enable population geneticists to analyze spatiotemporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.
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| 5. |
- Kramberger, Milica G., et al.
(författare)
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Subclinical white matter lesions and medial temporal lobe atrophy are associated with EEG slowing in a memory clinic cohort
- 2017
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457 .- 1872-8952. ; 128:9, s. 1575-1582
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the study was to describe the relationship between electroencephalographic (EEG) findings obtained by standardized visual analysis, subclinical white matter lesions (WML) and brain atrophy in a large memory clinic population.& para;& para;Methods: Patients with Alzheimer's disease (AD, n = 58), mild cognitive impairment (MCI, n = 141), subjective cognitive impairment (SCI, n = 194) had clinical, MRI based WML severity and regional atrophy assessments, and routine resting EEG recording. Background activity (BA) and episodic and continuous abnormalities were assessed visually in EEG.& para;& para;Results: WML (p = 0.006) and atrophy in medial temporal regions (MTA) (p = <0.001) were associated with slower BA in all diagnoses. WML were associated in SCI with total episodic EEG abnormalities (p = 0.03).& para;& para;Conclusions: EEG is associated with subclinical WML burden and cortical brain atrophy in a memory clinic population.& para;& para;Significance: Even the standard visually assessed EEG can complement a memory clinic diagnostic workup.
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| 6. |
- Overgaard, Rune V., et al.
(författare)
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Mathematical beta cell model for insulin secretion following IVGTT and OGTT
- 2006
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Ingår i: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 0090-6964 .- 1573-9686. ; 34:8, s. 1343-1354
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Tidskriftsartikel (refereegranskat)abstract
- Evaluation of beta cell function is conducted by a variety of glucose tolerance tests and evaluated by a number of different models with less than perfect consistency among results obtained from different tests. We formulated a new approximation of the distributed threshold model for insulin secretion in order to approach a model for quantifying beta cell function, not only for one, but for several different experiments. Data was obtained from 40 subjects that had both an oral glucose tolerance test (OGTT) and an intravenous tolerance test (IVGTT) performed. Parameter estimates from the two experimental protocols demonstrate similarity, reproducibility, and indications of prognostic relevance. Useful first phase indexes comprise the steady state amount of ready releasable insulin A(0) and the rate of redistribution k(rd), where both yield a considerable correlation (both r = 0.67) between IVGTT and OGTT estimates. For the IVGTT, A(0) correlates well (r = 0.96) with the 10 min area under the curve of insulin above baseline, whereas k(rd) represents a new and possibly more fundamental first phase index. For the useful second phase index gamma, a correlation of 0.75 was found between IVGTT and OGTT estimates.
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| 7. |
- Sachs, Mikkel Lindskov, et al.
(författare)
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Danish Physicians' Views on the Appropriateness of the Involvement of Patients with Type 2 Diabetes in Regulatory Decision Making : A Qualitative Study.
- 2019
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Ingår i: Pharmaceutical Medicine. - : Springer Science and Business Media LLC. - 1178-2595 .- 1179-1993. ; 33:2, s. 99-107
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Regulators, the pharmaceutical industry, and patient organizations expect an increased inclusion of patients' risk preferences in medical regulatory decisions, for example, with regard to market approval. Merging of input from patients with, for example, multiple sclerosis, with expertise from health professionals in regulatory decisions has already occurred. The complex task of involving larger and more heterogeneous patient populations (e.g. with diabetes mellitus, asthma), however, remains.OBJECTIVE: This study aimed to understand physicians' experiences with factors influencing patients with diabetes mellitus perceived risks of their medicines and to explore how physicians, based on these experiences, perceive patients with diabetes to be suited for involvement in regulatory decisions. This study will provide knowledge that can improve the inclusion of heterogeneous patient groups in regulatory decisions.METHODS: We conducted five semi-structured interviews with physicians with different types of experiences with patients' risk perceptions (for example, being in contact with individual patients vs. being involved in developing guidelines at the population level) and one focus group interview with eight general practitioners in Sjælland, Denmark. We applied a thematic analysis to explore physicians' experiences of the risk perceptions of patients with type 2 diabetes and their perceptions of patients' fitness for involvement in regulatory decisions.RESULTS: The risk perceptions and preferences of patients with diabetes were perceived to be rather diverse. Four drivers behind this diversity were described: past experiences, personality, prognosis ability, and knowledge. The legitimacy of patient preferences was not questioned, but the diversity of risk perceptions made the respondents question the existence of a uniform 'patient voice' useful for regulatory decision making.CONCLUSION: The respondents acknowledged the relevance and legitimacy of the patient perspective, but it was a concern that patient risk perceptions, at present, are too diverse to be included in regulatory decisions. Whether patients make regulatory decisions as perceived by physicians needs to be confirmed by future studies.
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| 8. |
- Sachs, Mikkel Lindskov, et al.
(författare)
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Risk Perceptions in Diabetic Patients Who Have Experienced Adverse Events : Implications for Patient Involvement in Regulatory Decisions.
- 2017
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Ingår i: Pharmaceutical Medicine. - : Springer Science and Business Media LLC. - 1178-2595 .- 1179-1993. ; 31:4, s. 245-255
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increasingly, patients are expected to influence decisions previously reserved for regulatory agencies, pharmaceutical companies, and healthcare professionals. Individual patients have previously represented their patient population when rare, serious adverse events (AEs) were weighed as part of a benefit-risk assessment. However, the degree of heterogeneity of the patient population is critical for how accurately they can be represented by individuals.OBJECTIVES: This study aims to explore patients' risk perception of rare, serious adverse effects of medicines with regard to blood glucose-lowering antidiabetics used by the individual patient.METHODS: Semi-structured interviews were conducted with 18 patients with diabetes with self-perceived serious, but not necessarily rare, AEs (e.g. stroke or valve or bypass surgery). The interviews explored the patients' history of disease, perceptions of the terms rare and serious, and overall levels of risk aversion. A thematic analysis of the interviews, including a consensus discussion, was carried out.RESULTS: Interestingly, respondents rarely made a clear distinction between medicines-induced AEs and complications related to disease progression. Concerns regarding AEs were apparently diverse but were systematically related to the personal experiences of the respondents. Respondents routinely ignored information about possible rare, serious AEs, unless it could be related to personal experience. In the absence of experience, concerns were focused on common and less serious AEs, thus disregarding rare and more serious events.CONCLUSION: The study suggests that experience of AEs, related to either medicines or disease, constitutes an important factor of patient risk perception. We therefore propose that serious adverse experiences should be added to the traditional panel of socioeconomic factors that are accounted for when patients are invited to give input on regulatory decisions.
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| 9. |
- Wallace, Megan A., et al.
(författare)
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The discovery, distribution, and diversity of DNA viruses associated with Drosophila melanogaster in Europe
- 2021
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Ingår i: Virus Evolution. - : Oxford University Press (OUP). - 2057-1577. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Drosophila melanogaster is an important model for antiviral immunity in arthropods, but very few DNA viruses have been described from the family Drosophilidae. This deficiency limits our opportunity to use natural host-pathogen combinations in experimental studies, and may bias our understanding of the Drosophila virome. Here, we report fourteen DNA viruses detected in a metagenomic analysis of 6668 pool-sequenced Drosophila, sampled from forty-seven European locations between 2014 and 2016. These include three new nudiviruses, a new and divergent entomopoxvirus, a virus related to Leptopilina boulardi filamentous virus, and a virus related to Musca domestica salivary gland hypertrophy virus. We also find an endogenous genomic copy of galbut virus, a double-stranded RNA partitivirus, segregating at very low frequency. Remarkably, we find that Drosophila Vesanto virus, a small DNA virus previously described as a bidnavirus, may be composed of up to twelve segments and thus represent a new lineage of segmented DNA viruses. Two of the DNA viruses, Drosophila Kallithea nudivirus and Drosophila Vesanto virus are relatively common, found in 2 per cent or more of wild flies. The others are rare, with many likely to be represented by a single infected fly. We find that virus prevalence in Europe reflects the prevalence seen in publicly available datasets, with Drosophila Kallithea nudivirus and Drosophila Vesanto virus the only ones commonly detectable in public data from wild-caught flies and large population cages, and the other viruses being rare or absent. These analyses suggest that DNA viruses are at lower prevalence than RNA viruses in D.melanogaster, and may be less likely to persist in laboratory cultures. Our findings go some way to redressing an earlier bias toward RNA virus studies in Drosophila, and lay the foundation needed to harness the power of Drosophila as a model system for the study of DNA viruses.
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