Identification of Proteins Associated with the Early Restoration of Insulin Sensitivity After Biliopancreatic Diversion.

Context: Insulin resistance (IR) is a risk factor for type 2 diabetes, diabetic kidney disease, cardiovascular disease and nonalcoholic steatohepatitis. Biliopancreatic diversion (BPD) is the most effective form of bariatric surgery for improving insulin sensitivity.

Objective: To identify plasma proteins correlating with the early restoration of insulin sensitivity after BPD.

Tissue-specific genes as an underutilized resource in drug discovery.

Tissue-specific genes are believed to be good drug targets due to improved safety. Here we show that this intuitive notion is not reflected in phase 1 and 2 clinical trials, despite the historic success of tissue-specific targets and their 2.3-fold overrepresentation among targets of marketed non-oncology drugs.

Human hepatic gene expression signature of non-alcoholic fatty liver disease progression, a meta-analysis.

Non-alcoholic fatty liver disease (NAFLD) is a wide-spread chronic liver condition that places patients at risk of developing cardiovascular diseases and may progress to cirrhosis or hepatocellular carcinoma if untreated. Challenges in clinical and basic research are caused by poor understanding of NAFLD mechanisms. The purpose of current study is to describe molecular changes occurring in human liver during NAFLD progression by defining a reproducible gene expression signature.

FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance.

Objective: To study effects of dexamethasone on gene expression in human adipose tissue aiming to identify potential novel mechanisms for glucocorticoid-induced insulin resistance.

Materials/methods: Subcutaneous and omental adipose tissue, obtained from non-diabetic donors (10 M/15 F; age: 28-60 years; BMI: 20.7-30.

GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and regulates somatostatin secretion from murine islets of Langerhans.

Aims/hypothesis: The NEFA-responsive G-protein coupled receptor 120 (GPR120) has been implicated in the regulation of inflammation, in the control of incretin secretion and as a predisposing factor influencing the development of type 2 diabetes by regulation of islet cell apoptosis. However, there is still considerable controversy about the tissue distribution of GPR120 and, in particular, it remains unclear which islet cell types express this molecule. In the present study, we have addressed this issue by constructing a Gpr120-knockout/β-galactosidase (LacZ) knock-in (KO/KI) mouse to examine the distribution and functional role of GPR120 in the endocrine pancreas.

Combining evidence of preferential gene-tissue relationships from multiple sources.

An important challenge in drug discovery and disease prognosis is to predict genes that are preferentially expressed in one or a few tissues, i.e. showing a considerably higher expression in one tissue(s) compared to the others.

Role of Escherichia coli curli operons in directing amyloid fiber formation.

Amyloid is associated with debilitating human ailments including Alzheimer's and prion diseases. Biochemical, biophysical, and imaging analyses revealed that fibers produced by Escherichia coli called curli were amyloid. The CsgA curlin subunit, purified in the absence of the CsgB nucleator, adopted a soluble, unstructured form that upon prolonged incubation assembled into fibers that were indistinguishable from curli.