GLUT4, AMP kinase, but not the insulin receptor, are required for hepatoportal glucose sensor-stimulated muscle glucose utilization.

Recent evidence suggests the existence of a hepatoportal vein glucose sensor, whose activation leads to enhanced glucose use in skeletal muscle, heart, and brown adipose tissue. The mechanism leading to this increase in whole body glucose clearance is not known, but previous data suggest that it is insulin independent. Here, we sought to further determine the portal sensor signaling pathway by selectively evaluating its dependence on muscle GLUT4, insulin receptor, and the evolutionarily conserved sensor of metabolic stress, AMP-activated protein kinase (AMPK). We demonstrate that the increase in muscle glucose use was suppressed in mice lacking the expression of GLUT4 in the organ muscle. In contrast, glucose use was stimulated normally in mice with muscle-specific inactivation of the insulin receptor gene, confirming independence from insulin-signaling pathways. Most importantly, the muscle glucose use in response to activation of the hepatoportal vein glucose sensor was completely dependent on the activity of AMPK, because enhanced hexose disposal was prevented by expression of a dominant negative AMPK in muscle. These data demonstrate that the portal sensor induces glucose use and development of hypoglycemia independently of insulin action, but by a mechanism that requires activation of the AMPK and the presence of GLUT4.

Priorities For Action 2002/03 (PDF 108 KB)

Priorities For Action 2002/03

Gut-derived signaling molecules and vagal afferents in the control of glucose and energy homeostasis.

PURPOSE OF REVIEW: The control of glucose and energy homeostasis, including feeding behaviour, is tightly regulated by gut-derived peptidic and nonpeptidic endocrine mediators, autonomic nervous signals, as well as nutrients such as glucose. We will review recent findings on the role of the gastrointestinal tract innervation and of portal vein glucose sensors; we will review selected data on the action of gastrointestinally released hormones. RECENT FINDINGS: The involvement of mechanosensory vagal afferents in postprandial meal termination has been clarified using mouse models with selective impairments of genes required for development of mechanosensory fibres. These activate central glucogen-like peptide-1/glucogen-like peptide-2 containing ascending pathways linking the visceroceptive brainstem neurons to hypothalamic nuclei. Mucosal terminals comprise the chemosensory vagal afferents responsive to postprandially released gastrointestinal hormones. The mechanism by which the hepatoportal glucose sensor stimulates glucose utilization by muscles was demonstrated, using genetically modified mice, to be insulin-independent but to require GLUT4 and AMP-kinase. This sensor is a key site of glucogen-like peptide-1 action and plays a critical role in triggering first phase insulin secretion. PeptideYY and ghrelin target intracerebral receptors as they are bidirectionally transported across the blood brain barrier. The anorectic functions of peripherally released peptideYY may however be mediated both via vagal afferents and intracerebral Y2 receptors in the brainstem and arcuate nucleus. SUMMARY: These recent findings demonstrate that the use of improved anatomical and physiological techniques and animal models with targeted gene modifications lead to an improved understanding of the complex role of gastrointestinal signals in the control of energy homeostasis.

Priorities For Action 2001/02 (PDF 77.3 KB)

Priorities For Action 2001/02

Action Plan for People Management in the Health Service

In November of 2001 the Government launched its new National Health Strategy â?" â?oQuality and Fairness, A Health System for youâ?Âù (hereafter referred to as Quality and Fairness). Quality and Fairness was developed following one of the largest consultation processes ever undertaken in the public service. It sets out the vision for the health service, the four principles upon which this vision will be built, it also establishes four National goals and finally sets out six â?~frameworks for changeâ?T, which will be used to achieve the vision, principles and goals. One of the six frameworks for change is Developing Human Resources. The health service is one of the largest employers in the public sector, with the employment level at the end of 2001 approaching 93,000 full time employees. These employees are spread across a large number of organisations, in multiple locations and settings across the country. Each employee plays a key role in the delivery of health service, in all settings, to the public. Download document here

Customer Service Action Plan

Customer Service Action Plan One of the fundamental themes of Delivering Better Government (1996) is the â?oachievement of an excellent service for the Government and for the public as customers and clients at all levelsâ?Âù. In 2000, the Quality Customer Service (QCS) Working Group reviewed and revised the 1997 Principles of Quality Customer Service to take account of changes in the environment since 1997, such as the equality agenda. In July 2000, the Government decided that: Click here to download PDF 199kb

From Vision to Action: strengthening the nursing contribution to public health

From Vision to Action: strengthening the nursing contribution to public health The starting point for this report is a belief that public health is everybodyâ?Ts business. This is reflected in recent policies in Northern Ireland and the Republic of Ireland where improvements in health services are recommended as one part of the many measures that are needed to create environments for healthy living. Click here to download PDF 890kb

From Vision to Action: strengthening the nursing contribution to public health

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Quality and Fairness - A Health System for You - Action Plan Progress Report 2003

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An Action Plan for Dementia

The Action Plan takes as its guiding principle the recognition of the individuality of the person with dementia and of his or her individual needs. This principle has informed and influenced the development of the plan. The needs and uniqueness of the person with dementia must be paramount when we talk of care and service provision. Action on the treatment of dementia can be delayed no longer. Given the increasing proportion of older people in the population and the higher prevalence of dementia in older age groups, action is needed now. This plan should serve as a model of best practice for the provision and planning of services to meet the individual needs of people with dementia and their carers Download the Report here

Quality and Fairness - A Health System for You - Action Plan Progress Report 2004

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