Article Index

Written by Dan Gwartney, MD
11 July 2006

Young children around the globe have all heard some variation of the tale of the princess who kissed the frog, transforming it into a prince. While there are surely some who have puckered up to an amphibian, whether in search of a charming prince or a psychedelic ride such as the one Homer Simpson enjoyed in the episode “Missionary: Impossible,” nobody would voluntarily kiss a Gila monster (Heloderma suspectum).
The Gila monster is one of only two poisonous lizards living in the Southwestern U.S. and portions of Mexico. The Gila kills its prey by chewing on victims, allowing a neurotoxin released in its saliva to mix with the blood of the bitten animal. In addition to a number of toxic and lethal components, other interesting factors have been discovered in the saliva of Gila monsters. Of the 20+ bioactive factors discovered, many play a role in incapacitating the Gila’s prey; yet others seem to play a role in digesting its captured meal. Of these, one molecule gained the notice of researchers, who developed it into a powerhouse drug used in humans.1

The GLP-1 Deficit
This molecule, called exendin-4, is a 39-amino acid long peptide that’s jointly marketed by Amylin™ Pharmaceuticals and Eli Lilly for the treatment of type 2 diabetes mellitus that’s not adequately controlled by oral drugs.2 Approved by the U.S. Food and Drug Administration in April 2005, the drug exenatide is marketed under the brand name Byetta®. Byetta is the first in an exciting class of drugs, called incretin mimetics, which offer hope to type 2 diabetics seeking more-than-better blood sugar control. Byetta and similar drugs coming down the research pipeline improve blood cholesterol and lipids, blood pressure and support a progressive, steady, continual weight loss.
Type 2 diabetics tend to gain weight easily and many of the current drugs add to the problem by promoting fat storage. Byetta appears to preserve and restore pancreatic beta cell function (the cells that make insulin in the body and naturally control blood sugars). It’s possible that the use of Byetta early in the course of type 2 diabetes may delay the onset of symptoms, reduce the added risk of cardiovascular catastrophes (strokes and heart attacks) and possibly “cure” the disease.
Type 2 diabetes used to be called “adult-onset diabetes,” but it’s now seen in younger populations.3 Though the onset isn’t fully understood, it’s associated with sedentary lifestyles, high levels of visceral fat (the kind that surrounds the organs inside the abdomen) and obesity. People usually experience a slow, progressive loss of insulin sensitivity, meaning it takes more and more insulin to achieve a normal control of blood sugar levels. Eventually, the body is maintaining high levels of insulin, which leads to a higher incidence of blocked arteries, fat gain, loss of vision, infections and higher blood pressure, among other problems. Over the course of time, the pancreas can no longer produce or secrete enough insulin and the consequences become very severe.4
Type 2 diabetics have been treated with a variety of oral drugs that either increase insulin secretion, increase peripheral insulin sensitivity (allowing insulin to function better at shuttling sugar into the muscle and other tissues) or preventing the digestion and absorption of carbohydrates from the diet.5 Unfortunately, there’s no ideal drug for type 2 diabetes as all of these drugs are associated with some side effects including nausea, low blood sugar, flatulence and diarrhea, etc.
Scientists have long been aware of a hormone called glucagon-like peptide-1 (GLP-1) that’s produced by cells in the small intestine and signals insulin production by the pancreas.6 Not only is GLP-1 very short acting (having a half-life of approximately 90 seconds), type 2 diabetics can’t produce as much during a meal.7,8 Scientists knew that if they could correct the GLP-1 deficit, they could make a big impact on the underlying problem in type 2 diabetes.