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(April 11, 2011—Toronto, ON) After we eat, the specialized cells lining our gastrointestinal tract send signals to the pancreas to promote the release of insulin. This helps move the elevated blood sugar (glucose) into cells, where it is stored and later used for energy.  But the story may be more complex than once thought, according to new research at Mount Sinai Hospital.
 
Scientists at the Samuel Lunenfeld Research Institute of Mount Sinai and colleagues in New York have shown that the mechanisms regulating glucose control are more adaptive than previously understood. The findings will help refine treatment strategies for Type 2 diabetes, a condition in which the body becomes numbed to the effects of insulin, causing abnormally high levels of sugar build up in the blood.
 
The study was published online today in the Journal of Clinical Investigation.
 
“What we’ve newly revealed is that insulin-producing beta cells are adaptable, and that they adjust their functions based on the type of information flowing from the gut to the pancreas,” said Dr. Daniel Drucker, Senior Lunenfeld investigator, Banting and Best Diabetes Centre-Novo Nordisk Chair in Incretin Biology and lead study author.
 
Recently, attention has turned to a new line of therapy usingsubstances called incretins for people with Type 2 diabetes.GLP-1 (glucagon-like peptide 1) and GIP (gastric inhibitory peptide) are two incretin hormones that help normalizeblood sugar by: influencing cells in the pancreas called beta cells; decreasing the release of glucagon (a hormone that controlsthe release of glucose from the liver after meals); promoting a feelingof fullness after a meal, and; slowingthe emptying of the stomach’s contents into theintestines,which lowers peak blood sugar levels.
 
To understand these mechanisms further and find out specifically how the gut communicates with the pancreas, Dr. Drucker and his team created new genetic strains of non-diabetic mice in which the normal incretin pathways were switched off (i.e., the effects of GLP-1 were inactivated), and observed the effects on glucose tolerance and blood sugar levels following administration of glucose.
 
“Surprisingly, the ability of the gut to communicate with the pancreas and enhance insulin secretion and glucose disposal remained substantially improved in these mice, despite elimination of GLP-1, glucagon and GIP action,” said Safina Ali, a PhD student in the Drucker lab and first author of the study. “This suggests that beta cells are able to adapt and recruit alternate pathways to communicate with the gut and regulate glucose control.”
 
The team identified additional nutrient-sensitive receptors that were increased or ‘activated’ on insulin-secreting beta cells, and where thus able to take over the role of classical incretin receptors for GLP-1 and GIP. “Our findings imply that the beta cell has considerable plasticity and resilience and can rapidly recruit other incretin-like, nutrient-sensitive mechanisms to increase insulin levels after a meal,” said Dr. Drucker.
 
The concept of plasticity in science has been typically associated with studies of the brain and its cells (called neurons), and implies that structures and cells can adapt and change, based on experience and need. For example, damage to certain areas of the brain after a stroke can be mitigated by finding alternate brain pathways to rewire and transmit information, which explains the ability of some stroke patients to recover their speech.
 
This is the first time, however, that such adaptive mechanisms have been observed in the communication system linking nutrient ingestion, gastrointestinal hormones, and beta cells of the pancreas.
 
“Our next step will be to determine exactly how this plasticity occurs and then apply this knowledge to diabetic cells,” said Dr. Drucker. “As several new therapies based on incretin action are now employed for the treatment of diabetes (DPP-4 inhibitors and GLP-1 receptor agonists), understanding how the beta cell responds to diverse signals arising from food ingestion may provide new opportunities for developing additional therapies to improve insulin secretion in patients with Type 2 diabetes.”
 
The study was supported by the Canadian Institutes of Health Research.
   
The incidence of Type 2 diabetes has reached epidemic proportions worldwide and is a leading cause of heart disease, stroke, blindness, kidney failure and limb amputation. Several studies have shown that lifestyle changes and appropriate pharmacologic therapy can significantly reduce the development of Type 2 diabetes in people at risk of the disease.
 
 
 

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