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Tendons are important load-bearing structures, which are frequently injured in both sports and work. Type I collagen fibrils are the primary components of tendons and carry most of the mechanical loads experienced by the tissue, however, knowledge of how load is transmitted between and within fibrils is limited. The presence of covalent enzymatic cross-links between collagen molecules is an import
Methods: A randomized, double-blind, active-comparator study of patients with type 2 diabetes mellitus inadequately controlled (HbA1c 6.5-8.5%) by metformin monotherapy. Patients received vildagliptin (50 mg twice daily) or glimepiride (up to 6 mg/day) added to metformin. Results: In all, 3118 patients were randomized (vildagliptin, n = 1562; glimepiride, n = 1556). From similar baseline values (7
With the expanding armamentarium of noninsulin therapies for type 2 diabetes mellitus, the use of insulin with various oral agents is becoming more common. In this study, we assessed the efficacy and cardiovascular (CV) safety of the dipeptidyl peptidase-4 inhibitor linagliptin as add-on to insulin in patients with type 2 diabetes.
Using a newly developed in vivo model measuring glucagon-like peptide-1 (GLP-1) in gut lymphatics in mice, we quantified GLP-1 secretion in vivo after glucose versus fat ingestion with and without concomitant DPP-4 inhibition. The mesenteric lymphatic duct was cannulated in anesthetized C57BL6/J mice and lymph was collected in 30min intervals. Glucose or fat emulsion (Intralipid(R)) (0.03, 0.1 or
AimsThe effects of sitagliptin and pioglitazone, alone and in combination, on - and -cell function were assessed in patients with type 2 diabetes. MethodsFollowing a 6-week diet/exercise period, 211 patients with HbA1c of 6.5-9.0% and fasting plasma glucose of 7.2-14.4mmol/l were randomized (1:1:1:1) to sitagliptin, pioglitazone, sitagliptin+pioglitazone or placebo. At baseline and after 12weeks,
The Environmental Determinants of Diabetes in the Young (TEDDY) study is designed to identify environmental exposures triggering islet autoimmunity and type 1 diabetes (T1D) in genetically high-risk children. We describe the first 100 participants diagnosed with T1D, hypothesizing that (i) they are diagnosed at an early stage of disease, (ii) a high proportion are diagnosed by an oral glucose tole
β cell dysfunction is central to the development and progression of type 2 diabetes (T2D). T2D develops when β cells are not able to compensate for the increasing demand for insulin caused by insulin resistance. Epigenetic modifications play an important role in establishing and maintaining β cell identity and function in physiological conditions. On the other hand, epigenetic dysregulation can ca
The peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. Several reports have shown that PPARdelta is involved in lipid metabolism, increasing fat oxidation and depleting lipid accumulation. Whether PPARdelta is involved in the regulation of glucose metabolism is not completely understood. In this study, we examined effects of
Randomised control trials (RCTs) do not always reflect real-life outcomes for glucose-lowering drugs. In this work we compared RCT and real-life data on the efficacy of the dipeptidyl peptidase-IV (DPP-4) inhibitor vildagliptin or sulfonylureas when added to metformin.
Obesity is increasing worldwide and is associated with increased risk of developing metabolic diseases. One of the factors that have been demonstrated to influence the regulation of appetite and food intake is the different sex hormones, one of these being progesterone that in humans increase food intake (Hirschberg, 2012). In this issue of Acta Physiologica, Holmberg and colleagues present their
Glucokinase (GK) plays a key role in maintaining glucose homeostasis by promoting insulin secretion from pancreatic beta cells and increasing hepatic glucose uptake. Here we investigate the effects of acute and chronic GK activation on glucose tolerance and insulin secretion in mice with diet-induced insulin resistance. In the acute study, a small molecule GK activator (GKA71) was administered to
Alkaline sphingomyelinase (alk-SMase) hydrolyses sphingomyelin (SM) to ceramide in the gut. To evaluate physiological importance of the enzyme, we generated alk-SMase knockout (KO) mice by Cre-LoxP system and studied SM digestion. Both wild type (WT) and the KO mice were fed 3H-palmitic acid labeled SM together with milk SM by gavage. The lipids in intestinal content, intestinal tissues, serum and
Mice genetically deficient in the glucagon receptor (Gcgr(-/-)) show improved glucose tolerance, insulin sensitivity and α-cell hyperplasia. In addition, Gcgr(-/-) mice do not develop diabetes after chemical destruction of β-cells. Since fibroblast growth factor 21 (FGF21) has insulin independent glucose lowering properties we investigated whether FGF21 was contributing to diabetes resistance in i
In experimental studies, enkephalins (ENKs) and related opioids have been implicated as negative regulators of breast cancer development by enhancing immune-mediated tumoral defense as well as directly inhibiting cancer cells. We hypothesized that plasma levels of ENKs are predictive of the long-term breast cancer risk. Therefore, our objective was to measure pro-ENK A, a surrogate for mature ENK,
Alternative splicing (AS) is a fundamental mechanism for the regulation of gene expression. It affects more than 90% of human genes but its role in the regulation of pancreatic beta cells, the producers of insulin, remains unknown. Our recently published data indicated that the 'neuron-specific' Nova1 splicing factor is expressed in pancreatic beta cells. We have presently coupled specific knockdo
The aim of this study is to explore whether administration timing affects glycaemic control by lixisenatide once-daily in type 2 diabetes mellitus (T2DM).
