Effects of Fructose Restriction on Liver Steatosis
Nonalcoholic Fatty Liver DiseaseGlucose Metabolism Disorders1 moreNonalcoholic fatty liver disease (NAFLD) is an emerging health problem as it can lead to end stage liver failure and cardiovascular complications. Diet play an important role in the development of NAFLD. Many studies have addressed the effects of added fructose on NAFLD. To date, little attention has been paid to the effects of a diet devoid of fructose. Therefore, the investigators aim to study the effects of fructose restriction on hepatic fat accumulation and vascular function using a double-blind randomized placebo-controlled design.
Hyperglycemia and Exercise.
Aerobic ExerciseHyperglycemia1 moreThis study will determine whether exposure to short-term high blood glucose levels impairs exercise-induced adaptations in glucose tolerance, and whether the pattern of high blood glucose levels plays a role.
Delineation of the Role of Glucagon-like Peptide-1 Signalling in Relation to Increased Carbohydrate...
Glucose Metabolism DisordersInvestigation of GLP-1 signalling in the glucose-lowering effect of increased carbohydrate content in the distal small intestines induced by alpha-glucosidase inhibition during meal ingestion in patients with type 2 diabetes
The Role of GLP-1 Receptor Signalling in the Glucose-lowering Effect of Metformin in Patients With...
Glucose Metabolism DisordersDelineation of the role of glucagon-like peptide-1 receptor signalling in the glucose-lowering effect of metformin during meal ingestion in patients with type 2 diabetes.
Glucagon Resistance in Patients With NAFLD
Non-Alcoholic Fatty Liver DiseaseNon-alcoholic Steatohepatitis1 moreThe investigators propose that the sensitivity to glucagon in hepatic lipid metabolism is impaired in subjects with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). Moreover, they propose a dys-coordinated, reduced glucagon sensitivity in hepatic lipid metabolism and endogen glucose production in patients with NAFLD and NASH compared with healthy subjects and patients with simple steatosis. This reduced sensitivity may be the basis of a more severe dyslipidemia and the production of increased concentrations of toxic lipid intermediates in plasma and muscle tissue. The study will include healthy subjects with obesity and subjects with simple steatosis and NASH, tested at basal glucagonemia and moderate hyperglucagonemia to mimic insulin resistant levels during simultaneous somatostatin infusion and replacement doses of insulin and growth hormone. Infusion of palmitate, VLDL-triglyceride and glucose tracers in combination with indirect calorimetry as well as skeletal and adipose tissue biopsies will be employed to assess free fatty acid and VLDL-triglyceride kinetics (turnover, and oxidation) and hepatic fatty acid-esterification.
Training in the Fasted State, Glucose Metabolism and Energy Balance
Glucose Metabolism DisordersIn healthy individuals, the body responds to glucose (sugar) ingestion by reducing the amount released from the liver. At the same time, skeletal muscles increase the rate at which they remove the glucose from the bloodstream, via the actions of the hormone insulin. This ensures that blood glucose levels remain in a controlled range. However, in developed countries, diseases such as metabolic syndrome and type 2 diabetes are becoming prevalent, due to dietary modifications and a reduction in physical activity. As one of the prominent barriers to regular physical activity is a lack of time, finding ways to maximize the health benefits of exercise is a priority for researchers. The investigators want to understand potential differences in the effects of six weeks of aerobic training, with the exercise performed either after breakfast or after a prolonged fast. Specifically, this research aims to investigate whether there is a difference in the change in processes implicated in glucose regulation and secondly, in subsequent eating and physical activity behaviors. By investigating these changes this work will explore how exercise and nutrition can be optimized to benefit health and weight loss.
Lipolytic Effects of GH in Hypopituitary Patients in Vivo
HypopituitarismInsulin Resistance5 moreGrowth hormone (GH) is essential for longitudinal bone growth and somatic development. These protein anabolic effects require sufficient nutritional supply. During fasting and caloric restriction GH predominantly promotes fat metabolism. GH counteracts the effect of insulin in many tissues, of which insulin-stimulated glucose uptake in skeletal muscle has been most extensively studied. Substrate competition between elevated free fatty acids and glucose is suggested as a mechanism, and this hypothesis can be tested mechanistically by means of acipimox, which is a nicotinic acid that suppresses the fat metabolizing effects of GH. The hypothesis is, that the suppressive effect of GH on insulin-stimulated glucose uptake in skeletal muscle is obviated by acipimox-induced inhibition of fat metabolism. In order to investigate this, eight adult hypopituitary patients with documented GH-deficiency will be studied in the presence and absence of GH and acipimox, respectively, and biopsies from skeletal muscle and subcutaneous adipose tissue will be analyzed. Knowledge of the effects of growth hormone and fat metabolism can in shot-sight as well as in long-sight have great importance for the understanding of growth disorders from overweight and type 2 diabetes to malnutrition and eating disorders.
A Single Dose Study In Japanese And Western Healthy Subjects To Investigate The Safety, Tolerability...
Diabetes MellitusDiabetes Mellitus2 moreThis study is to investigate the safety, tolerability and pharmacokinetics of single ascending oral doses of PF-04991532 in Japanese healthy subjects. The secondary objective is to investigate the pharmacokinetics and safety of single ascending oral doses of PF-04991532 in Western healthy subjects and to compare the pharmacokinetics between Japanese and Western healthy subjects.
Multiple Dose Study of PF-04991532 in Patients With Type 2 Diabetes
Diabetes MellitusDiabetes Mellitus2 moreThe purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-04991532 following multiple (14 days) escalating oral doses in patient wtih type 2 diabetes.
Effects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance
Glucose Metabolism DisordersDiabetesSubjects with impaired glucose tolerance will be randomized to receive pioglitazone or metformin for 10 weeks. Measurements of insulin sensitivity, body composition, glucose tolerance, and muscle lipid accumulation will be performed. Adipose tissue and muscle biopsies are performed. The goal of the study is to determine whether the lipotoxiciy of impaired glucose tolerance is ameliorated by pioglitazone.