Multiple promoter and enhancer differences likely contribute to augmented G6PC2 expression in human versus mouse pancreatic islet alpha cells.

G6PC2 encodes a glucose-6-phosphatase catalytic subunit that opposes the action of glucokinase in pancreatic islets, thereby modulating the sensitivity of insulin and glucagon secretion to glucose. In mice, G6pc2 is expressed at ~20-fold higher levels in β-cells than in α-cells, whereas in humans G6PC2 is expressed at only ~5-fold higher levels in β-cells. We therefore hypothesize that G6PC2 likely influences glucagon secretion to a greater degree in humans.

A novel dual balloon rectal catheter for use in the postoperative assessment of low rectal anastomoses following low anterior resection.

Following low anterior resection (LAR) of the colon, an image-guided assessment of the anastomosis for leak is typically performed using an enema via a rectal catheter, whether by CT or fluoroscopy. However, there is potential for poor assessment due to inappropriate catheter positioning as well as potential risk that the anastomosis becomes compromised by the balloon inflation. This article discusses the adaptation of a novel double-balloon catheter (originally designed by a member of our institution for use in pediatric intussusception reduction) for assessment of low rectal anastomoses.

Added value of iodine-specific imaging and virtual non-contrast imaging for gastrointestinal assessment using dual-energy computed tomography.

Dual-energy computed tomography (DECT) has become increasingly available and can be readily incorporated into clinical practice. Although DECT can provide a wide variety of spectral imaging reconstructions, most clinically valuable information is available from a limited number of standard image reconstructions including virtual non-contrast and iodine overlay. The combination of these standard reconstructions can be used for specific diagnostic tasks that provide added value over traditional CT protocols.

Multi-Center Follow-up Study to Develop a Classification System Which Differentiates Mucinous Cystic Neoplasm of the Liver and Benign Hepatic Cyst Using Machine Learning.

Rationale And Objectives: To date, no clinically useful classification system has been developed for reliably differentiating mucinous cystic neoplasm (MCN) from a benign hepatic cyst (BHC) in the liver. The objective was to use machine learning and a multi-center study design to develop and assess the performance of a novel classification system for predicting whether a hepatic cystic lesion represents MCN or BHC.

Materials And Methods: A multi-center cohort study identified 154 surgically resected hepatic cystic lesions in 154 subjects which were pathologic confirmed as MCN (43) or BHC (111).

Non-contrast and portal venous phase computed tomography in breast cancer hepatic metastases: comparison of tumor measurements and impact on response assessment.

Background: For many common malignancies, including breast cancer, evaluation for metastatic disease using multiphase computed tomography (CT) has fallen out of favor and been replaced by studies performed only in the portal venous phase. However, differences in tumor vascularity could produce differences in appearance on post-contrast imaging.

Purpose: To assess non-contrast phase and portal venous phase computed tomography in detection and measurement of hepatic metastases from breast carcinoma.

Combined Qualitative and Quantitative Assessment of Low-Attenuation Renal Lesions Improves Identification of Renal Malignancy on Noncontrast Computed Tomography.

Objective: The objective of this study was to assess renal lesions measuring less than 20 Hounsfield units (HU) on noncontrast computed tomography (NCT).

Methods: Twenty-one (18.1%) of 116 consecutive pathologically proven renal cell carcinomas measured less than 20 HU on NCT and were compared with 40 confirmed benign cysts also measuring less than 20 HU.

Limitation of Virtual Noncontrasted Images in Evaluation of a Liver Lesion Status Post Transarterial Chemoembolization.

The authors describe a case of a patient with a solitary hepatocellular carcinoma status post transarterial chemoembolization. Follow-up imaging was performed using dual-energy computed tomography. The study was performed with and without contrast and a virtual noncontrast data set was constructed from the postcontrast images.

Genetic and functional assessment of the role of the rs13431652-A and rs573225-A alleles in the G6PC2 promoter that are strongly associated with elevated fasting glucose levels.

Objective: Genome-wide association studies have identified a single nucleotide polymorphism (SNP), rs560887, located in a G6PC2 intron that is highly correlated with variations in fasting plasma glucose (FPG). G6PC2 encodes an islet-specific glucose-6-phosphatase catalytic subunit. This study examines the contribution of two G6PC2 promoter SNPs, rs13431652 and rs573225, to the association signal.

Insulin and epidermal growth factor suppress basal glucose-6-phosphatase catalytic subunit gene transcription through overlapping but distinct mechanisms.

The G6Pase (glucose-6-phosphatase catalytic subunit) catalyses the final step in the gluconeogenic and glycogenolytic pathways, the hydrolysis of glucose-6-phosphate to glucose. We show here that, in HepG2 hepatoma cells, EGF (epidermal growth factor) inhibits basal mouse G6Pase fusion gene transcription. Several studies have shown that insulin represses basal mouse G6Pase fusion gene transcription through FOXO1 (forkhead box O1), but Stoffel and colleagues have recently suggested that insulin can also regulate gene transcription through FOXA2 (forkhead box A2) [Wolfrum, Asilmaz, Luca, Friedman and Stoffel (2003) Proc.

Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression.

Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes. IGRP is selectively expressed in islet beta cells and polymorphisms in the IGRP gene have recently been associated with variations in fasting blood glucose levels and cardiovascular-associated mortality in humans. Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2.

Long-range enhancers are required to maintain expression of the autoantigen islet-specific glucose-6-phosphatase catalytic subunit-related protein in adult mouse islets in vivo.

Objective: Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is selectively expressed in islet beta-cells and is a major autoantigen in both mouse and human type 1 diabetes. This study describes the use of a combination of transgenic and transfection approaches to characterize the gene regions that confer the islet-specific expression of IGRP.

Research Design And Methods: Transgenic mice were generated containing the IGRP promoter sequence from -306, -911, or -3911 to +3 ligated to a LacZ reporter gene.

Gluconeogenesis: re-evaluating the FOXO1-PGC-1alpha connection.

Increased expression of the gene encoding the enzyme glucose-6-phosphatase (G6Pase) contributes to the increased production of glucose by the liver that occurs in individuals with diabetes. Puigserver et al. show that the transcription factor FOXO1 and the transcriptional co-activator PGC-1alpha act synergistically to stimulate the expression of genes in the gluconeogenesis pathway and propose that PGC-1alpha acts, in part, directly through FOXO1.