Role of KATP channels in glucose-regulated glucagon secretion and impaired counterregulation in type 2 diabetes.

Glucagon, secreted by pancreatic islet α cells, is the principal hyperglycemic hormone. In diabetes, glucagon secretion is not suppressed at high glucose, exacerbating the consequences of insufficient insulin secretion, and is inadequate at low glucose, potentially leading to fatal hypoglycemia. The causal mechanisms remain unknown.

Insights into the molecular mechanism for type 2 diabetes susceptibility at the KCNQ1 locus from temporal changes in imprinting status in human islets.

The molecular basis of type 2 diabetes predisposition at most established susceptibility loci remains poorly understood. KCNQ1 maps within the 11p15.5 imprinted domain, a region with an established role in congenital growth phenotypes.

Mapping cis- and trans-regulatory effects across multiple tissues in twins.

Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many expression quantitative trait locus (eQTL) studies, typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a large set of mono- and dizygotic twins that allows systematic dissection of genetic (cis and trans) and non-genetic effects on gene expression.

Reduced insulin exocytosis in human pancreatic β-cells with gene variants linked to type 2 diabetes.

The majority of genetic risk variants for type 2 diabetes (T2D) affect insulin secretion, but the mechanisms through which they influence pancreatic islet function remain largely unknown. We functionally characterized human islets to determine secretory, biophysical, and ultrastructural features in relation to genetic risk profiles in diabetic and nondiabetic donors. Islets from donors with T2D exhibited impaired insulin secretion, which was more pronounced in lean than obese diabetic donors.

Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes.

Metabolic Syndrome (MetS) is highly prevalent and has considerable public health impact, but its underlying genetic factors remain elusive. To identify gene networks involved in MetS, we conducted whole-genome expression and genotype profiling on abdominal (ABD) and gluteal (GLU) adipose tissue, and whole blood (WB), from 29 MetS cases and 44 controls. Co-expression network analysis for each tissue independently identified nine, six, and zero MetS-associated modules of coexpressed genes in ABD, GLU, and WB, respectively.

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

Objective: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology.

Type 2 diabetes and obesity: genomics and the clinic.

Type 2 diabetes (T2D) and obesity represent major challenges for global public health. They are at the forefront of international efforts to identify the genetic variation contributing to complex disease susceptibility, and recent years have seen considerable success in identifying common risk-variants. Given the clinical impact of molecular diagnostics in rarer monogenic forms of these diseases, expectations have been high that genetic discoveries will transform the prospects for risk stratification, development of novel therapeutics and personalised medicine.

Valuing goodwill: not-for-profits prepare for annual impairment testing.

Accounting standards for valuing goodwill and intangible assets are becoming more rigorous for not-for-profit organizations: Not-for-profit healthcare organizations need to test for goodwill impairment at least annually. Impairment testing is a two-stage process: initial analysis to determine whether impairment exists and subsequent calculation of the magnitude of impairment. Certain "triggering" events compel all organizations--whether for-profit or not-for-profit--to perform an impairment test for goodwill or intangible assets.

The architecture of gene regulatory variation across multiple human tissues: the MuTHER study.

While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL), skin, and fat. The samples (156 LCL, 160 skin, 166 fat) were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource.

FASB issues new accounting standards for business combinations.

Accounting Standard Codification Topic 958 (formerly Financial Accounting Standards Board Statement No. 164), Not-for-Profit Entities: Mergers and Acquisitions, applies to mergers and acquisitions as early as Jan. 1, 2010, for calendar-year entities.