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Development and optimization of a metabolomic method for analysis of adherent cell cultures

In this investigation, a gas chromatography/mass spectrometry (GC/MS)-based metabolomic protocol for adherent cell cultures was developed using statistical design of experiments. Cell disruption, metabolite extraction, and the GC/MS settings were optimized aiming at a gentle, unbiased, sensitive, and high-throughput metabolomic protocol. Due to the heterogeneity of the metabolome and the inherent

Physiological aspects of the combination of insulin and GLP-1 in the regulation of blood glucose control.

Combining insulin with glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors as glucose-lowering therapy for type 2 diabetes is a promising strategy that has gained considerable interest over the past few years. One advantage of this combination is the complementary mechanistic actions of insulin and GLP-1. Insulin increases glucose utilization and retards

Glucose-dependent insulinotropic polypeptide lowers branched chain amino acids in hyperglycemic rats.

Hypersecretion of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) has been associated with obesity and glucose intolerance. This condition has been suggested to be linked to GIP resistance. Besides its insulinotropic effect, GIP also directly affects glucose uptake and lipid metabolism. This notwithstanding, effects of GIP on other circulating metabolites than glucose have

Vaccines against atherosclerosis.

Atherosclerosis is the primary cause of acute myocardial infarction and stroke. It is well established that arterial inflammation in response to accumulation and oxidation of lipoproteins in the vascular wall is the major factor responsible for the development of atherosclerosis. During recent years, it has become apparent that this vascular inflammation is modulated by a complex array of autoimmu

A fossil winonaite-like meteorite in Ordovician limestone: A piece of the impactor that broke up the L-chondrite parent body?

About a quarter of all meteorites falling on Earth today originate from the breakup of the L-chondrite parent body similar to 470 Ma ago, the largest documented breakup in the asteroid belt in the past similar to 3 Ga. A window into the flux of meteorites to Earth shortly after this event comes from the recovery of about 100 fossil L chondrites (1-21 cm in diameter) in a quarry of mid-Ordovician l

Short- and Long-Term Hormonal and Metabolic Consequences of Reversing Gastric Bypass to Normal Anatomy in a Type 2 Diabetes Patient.

Gastric bypass (GBP) results in rapid type 2 diabetes (T2D) remission in most cases. Consequences of GBP reversal are unknown. A GBP-operated T2D patient was given mixed-meal tests before (MMTpre), 2 months (MMT2-M) and 12 months (MMT12-M) after GBP reversal. Glucose, hormones and metabolite profiles were assessed. MMT2-M displayed slightly lower glucose levels; MMT12-M displayed higher glucose an

Invited commentary: Gene x lifestyle interactions and complex disease traits--inferring cause and effect from observational data, sine qua non.

Observational epidemiology has made outstanding contributions to the discovery and elucidation of relations between lifestyle factors and common complex diseases such as type 2 diabetes. Recent major advances in the understanding of the human genetics of this disease have inspired studies that seek to determine whether the risk conveyed by bona fide risk loci might be modified by lifestyle factors

Genetic and morphological differentiation across a contact zone between two postglacial immigration lineages of Helianthemum nummularium (Cistaceae) in southern Scandinavia

Helianthemum nummularium (L.) Mill. has two subspecies in southern Scandinavia, which differ in an indumentum character that is inherited as a Mendelian gene with two alleles. The dominant allele is the genetic basis for the key character of subsp. obscurum (absence of a dense felt of stellate hairs on the abaxial surface of the leaf), whereas the recessive allele is the genetic basis for the key

AMPK alpha 1 Regulates Macrophage Skewing at the Time of Resolution of Inflammation during Skeletal Muscle Regeneration

Macrophages control the resolution of inflammation through the transition from a proinflammatory (M1) to an anti-inflammatory (M2) phenotype. Here, we present evidence for a role of AMPK alpha 1, a master regulator of energy homeostasis, in macrophage skewing that occurs during skeletal muscle regeneration. Muscle regeneration was impaired in AMPK alpha 1(-/-) mice. In vivo loss-of-function (LysM-

The Complement Inhibitor CD59 Regulates Insulin Secretion by Modulating Exocytotic Events.

Type 2 diabetes is triggered by reduced insulin production, caused by genetic and environmental factors such as inflammation originating from the innate immune system. Complement proteins are a component of innate immunity and kill non-self cells by perforating the plasma membrane, a reaction prevented by CD59. Human pancreatic islets express CD59 at very high levels. CD59 is primarily known as a

On depolarization-evoked exocytosis as a function of calcium entry: possibilities and pitfalls.

Secretion from many endocrine cells is a result of calcium-regulated exocytosis due to Ca(2+) influx. Using the patch-clamp technique, voltage pulses can be applied to the cells to open Ca(2+) channels, resulting in a measurable Ca(2+) current, and evoke exocytosis, which can be seen as an increase in membrane capacitance. A common tool for evaluating the relation between Ca(2+) influx and exocyto

Diverse roles for CDK-associated activity during spermatogenesis

The primary function of cyclin-dependent kinases (CDKs) in complex with their activating cyclin partners, is to promote mitotic division in somatic cells. This canonical cell cycle-associated activity is also crucial for fertility as it allows the proliferation and differentiation of stem cells within the reproductive organs to generate meiotically competent cells. Intriguingly several CDKs exhibi

Conceptualising the Cosmos : Development and Validation of the Cosmology Concept Inventory for High School

Cosmology concepts encompass complex spatial and temporal relations that are counterintuitive. Cosmology findings, because of their intrinsic interest, are often reported in the public domain with enthusiasm, and students come to cosmology with a range of conceptions some aligned and some at variance with the current science. This makes cosmology concepts challenging to teach, and also challenging

Pre-electoral coalitions, familiarity, and delays in government formation

During the past decade, many parliamentary democracies have experienced bargaining delays when forming governments. The previous literature has attributed protracted government formation processes to a high degree of preference uncertainty among the political parties and a high level of bargaining complexity. The article draws on such theories, but also adds a third theoretical mechanism, commitme