Unlocking the clinical link with diabetes
While it had been known for some time that obesity was probably the most important factor in the development of insulin resistance, the chain of events was not fully understood until researchers at the Salk Institute for Biological Studies in San Diego identified the missing link between obesity and diabetes.
Their findings, published in the June 21, 2009 advance online edition of the journal Nature The Salk team, led by Prof Marc Montminy, a professor in the Clayton Foundation Laboratories for Peptide Biology in the Institute, discovered how a condition known as endoplasmic reticulum (ER) stress, which is induced by a high-fat diet and is overly activated in obese people, triggers aberrant glucose production in the liver, an important step on the way to insulin resistance. ER is basically a protein factory within the cell.
In healthy people, a ‘fasting switch’ only flips on glucose production in the liver when blood glucose levels run low during fasting. The existence of an alternate route that can modulate glucose production presents the potential to identify new classes of drugs that might help to lower blood sugar by disrupting this alternative pathway, Prof Montminy said. It had been previously established that obesity promotes insulin resistance through the inappropriate inactivation of a process called gluconeogenesis, where the liver creates glucose for fuel and which ordinarily occurs only in times of fasting.
Yet, not all obese people become insulin resistant, and insulin resistance occurs in non-obese individuals, leading Prof Montminy and his colleagues to suspect that fasting-induced glucose production was only half the story.
ER stress-response process “When a cell starts to sense stress, a ‘red light’ goes on, which slows down the production of proteins,” Prof Montminy explained in the study. “This process, which is known as ER stress response, is abnormally active in livers of obese individuals, where it contributes to the development of hyperglycaemia, or high blood glucose levels.”
To test whether chronic ER stress in obesity leads to abnormal activation of the fasting switch, the researchers asked whether ER stress could induce gluconeogenesis in lean mice.
A transcriptional switch called CRTC2, which normally sits outside the nucleus waiting for the signal that allows it to slip inside and do its work, turns on glucose production. Once in the nucleus, it teams up with a protein called CREB and they switch on the genes necessary to increase glucose output. In insulin-resistant mice, however, the CRTC2 switch seems to get stuck in the ‘on’ position and the cells start churning out glucose in overdrive.
Pharmacologic Stress Test - News
Adenosine is a coronary vasculature in Phase III development as a pharmacologic stress agent for radionuclide myocardial perfusion. Aspect 1 and aspect 2 are the 2 non-inferiority pivotal studies comparing apadenoson to Adenoscan and the primary
“This process, which is known as ER stress response, is abnormally active in livers of obese individuals, where it contributes to the development of hyperglycaemia, or high blood glucose levels.” To test whether chronic ER stress in obesity leads to
Pharmacological (ie, prednisolone) and physiological (ie, hydrocortisone) glucocorticoids display different properties. Stress doses of hydrocortisone reprogram rather than inhibit immune cells. 5 Corticosteroid effects depend on the inflammatory
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Pharmacologic Stress Test - Bookshelf
Beating Heart Disease: Strategies for a healthy heart
These women may benefit from a pharmacologic stress test (see below), which uses medications instead of exercise to make the heart work harder. ...Nuclear cardiology, practical applications
In addition, when compared to pharmacologic stress testing, exercise is associated with less extensive hepatic and gastrointestinal tracer uptake, ...The women's healthy heart program, lifesaving strategies for preventing and healing heart disease
Pharmacological Stress Tests If you cannot do enough walking, running, or pedaling to allow ... If you have asthma and need a pharmacological stress test, ...The ESC Textbook of Cardiovascular Imaging
Likelihood of functional recovery after PCI Pharmacological Stress Testing Although exercise testing is more physiologic than pharmacologic stress, ...Evidence-Based Cardiology
PHARMACOLOGIC STRESS TESTING WITH IMAGING Pharmacologic stress testing with imaging is indicated in patients with severe physical limitations. ...Detailed Information Directory
Pharmacologic Stress Testing - Care Guide
Care guide for Pharmacologic Stress Testing possible causes, signs and symptoms, standard treatment options and means of care and support.
Pharmacologic Stress Testing
Exercise testing is a cardiovascular stress test using treadmill bicycle exercise with ECG and blood pressure monitoring.
Pharmacologic Stress Test for Heart Disease - Heart Disease ...
People who can't take a stress test for heart disease may be able to do a pharmacologic stress test. For this test, medication is used to test heart functions.
Pharmacologic Stress Test with Nuclear Imaging
You may eat a light meal up to two hours before your stress test. ... During the pharmacologic. stress, just as in a regular stress test, your electrocardiogram ...
CardioSmart: Stress Testing(2)
A stress test helps show whether enough blood flows to your heart when it's working hard. ... During a stress test, your heart is monitored using images or through ...