Acute but not chronic activation of brain glucagon-like peptide-1 receptors enhances glucose-stimulated insulin secretion in mice.

AIM: To investigate the role of brain glucagon-like peptide-1 (GLP-1) in pancreatic ß-cell function. METHODS: To determine the role of brain GLP-1 receptor (GLP-1R) on ß-cell function, we administered intracerebroventricular (i.c.v.) infusions of GLP-1 or the specific GLP-1 antagonist exendin-9 (Ex-9), in both an acute and a chronic setting. RESULTS: We observed that acute i.c.v. GLP-1 infusion potentiates glucose-stimulated insulin secretion (GSIS) and improves glucose tolerance, whereas central GLP-1R blockade with Ex-9 impaired glucose excursion after a glucose load. Sustained activation of central nervous system GLP-1R, however, did not produce any effect on either GSIS or glucose tolerance. Similarly, ex vivo GSIS performed in islets from mice chronically infused with i.c.v. GLP-1 resulted in no differences compared with controls. In addition, in mice fed a high-fat diet we observed that acute i.c.v. GLP-1 infusion improved glucose tolerance without changes in GSIS, while chronic GLP-1R activation had no effect on glucose homeostasis. CONCLUSIONS: Our results indicate that, under non-clamped conditions, brain GLP-1 plays a functional neuroendocrine role in the acute regulation of glucose homeostasis in both lean and obese rodents.

Reprogramming gut and pancreas endocrine cells to treat diabetes.

Multiple approaches have been investigated with the ultimate goal of providing insulin independence to patients with either type 1 or type 2 diabetes. Approaches to produce insulin-secreting cells in culture, convert non-ß-cells into functional ß-cells or engineer autologous cells to express and secrete insulin in a meal-responsive manner have all been described. This research has been facilitated by significant improvements in both viral and non-viral gene delivery approaches that have enabled new experimental strategies. Many studies have examined possible avenues to confer islet cytoprotection against immune rejection, inflammation and apoptosis by genetic manipulation of islet cells prior to islet transplantation. Here we review several reports based on the reprogramming of pancreas and gut endocrine cells to treat diabetes.

Automated use of WHONET and SaTScan to detect outbreaks of Shigella spp. using antimicrobial resistance phenotypes.

Antimicrobial resistance is a priority emerging public health threat, and the ability to detect promptly outbreaks caused by resistant pathogens is critical for resistance containment and disease control efforts. We describe and evaluate the use of an electronic laboratory data system (WHONET) and a space-time permutation scan statistic for semi-automated disease outbreak detection. In collaboration with WHONET-Argentina, the national network for surveillance of antimicrobial resistance, we applied the system to the detection of local and regional outbreaks of Shigella spp. We searched for clusters on the basis of genus, species, and resistance phenotype and identified 19 statistical 'events' in a 12-month period. Of the six known outbreaks reported to the Ministry of Health, four had good or suggestive agreement with SaTScan-detected events. The most discriminating analyses were those involving resistance phenotypes. Electronic laboratory-based disease surveillance incorporating statistical cluster detection methods can enhance infectious disease outbreak detection and response.