Diabetes and the Pancreas

The pancreas functions as a linchpin in some of the biggest medical crises that we face, including with diabetes and obesity.

Should anybody in the reliably pestilent health care debate be casting about for a mascot organ to represent some of the biggest medical crises that we face, allow me to nominate a nonobvious candidate: the pancreas.

It may lie in the hidden depths of the abdominal cavity, and its appearance, size and purpose may be obscure to the average person. Yet the pancreas turns out to be a linchpin in two epidemics that are all too familiar.

As the organ entrusted with the manufacture of insulin and other hormones that help control blood sugar, the pancreas gone awry is a source of diabetes, which afflicts more than 23 million people in the United States. The World Health Organization estimated the global figure in 2000 at 171 million, and projected that by 2030, 366 million would be affected. And as the tireless brewer of digestive juices that help shear apart the amalgamated foodstuffs that we consume each day, the pancreas is at the frontlines of obesity.

Researchers are discovering that the pancreas helps mediate much of the appetite-related cross talk between the brain and the gastrointestinal tract, the streams of chemical signals that say, I'm starving down here, how about some dinner, or, enough already, step away from that dessert cart and no one will be hurt. By better understanding the precise role of the pancreas in conveying sensations of hunger or satiety, suggested Rodger A. Liddle of Duke University Medical School, we may find new ways to combat obesity.

Other researchers are intrigued by the pancreas' ability to shield itself from harm, to churn out huge quantities of enzymes that can rapidly reduce a cheeseburger and fries to so many particles of amino acids, carbohydrates and fats, without digesting its own tissue in the process. They suspect that the organ's set of self-protective mechanisms has a terrible downside, and helps explain why pancreatic cancer can be so difficult to treat -- insights that are just beginning to offer hope in the fight against one of the most lethal of all malignancies.

Early anatomists were certainly aware of the pancreas but mostly ignored it, and the organ's name reflects that ho-hum attitude. Pancreas is Greek for all-meat, a reference to its seeming homogeneity from one end to the other.

Much of the neglect may well have been practical. "The pancreas has always been difficult to study," Dr. Liddle said. For one thing, it's hidden. Measuring some 6 to 8 inches, or 15 to 20 centimeters, in length, and slippery and lobular to the touch, the yellowish- brown pancreas is located deep in the abdomen, wedged between the stomach and the spinal cord and extending horizontally right above the waistline. Think of it as an oblong eel.

Add to that inaccessibility a prima donna sensitivity. "If you do anything to the pancreas, you initiate an inflammatory response," Dr.Liddle said. "It tends to become inflamed more easily than other organs."

In fact, inflammation of the pancreas, or pancreatitis, is a relatively common and often debilitating condition, brought on by excess alcohol, drug reactions, gallstones, genetic predisposition or other reasons. Unfortunately, said Dr. Anthony Kalloo, a professor of medicine at the Johns Hopkins University School of Medicine, the symptoms of pancreatitis, like chronic abdominal pain radiating into the back, could be misdiagnosed or dismissed as a hypochondriac's lament.

As a result, Dr. Kalloo said, patients do not always receive the right pain medications, the optimal diet, surgery when necessary.

For all the difficulty of studying the pancreas, researchers eventually came to appreciate the organ as a gland of many talents, serving both an exocrine role -- secreting its products through ducts, as the breast secretes milk and the sweat glands perspiration -- and an endocrine role, fabricating hormones and squirting them into the bloodstream, as the ovaries and testes dispense sex hormones and the thyroid thyroxine.

Roughly 90 percent of the pancreas is devoted to its exocrinic role of generating digestive enzymes and funneling them into the small intestine, a burbling broth that flows forth from the pancreas at a rate of perhaps a quart a day.

The other 10 percent of pancreatic tissue consists of so-called islet cells, the endocrine players that synthesize insulin and glucagon to manipulate and titrate blood sugar, the body's energy currency, as needed. In people with Type 1, or juvenile-onset, diabetes -- among them Justice Sonia Sotomayor of the Supreme Court - - an autoimmune reaction ends up destroying many of these islet cells, resulting in the need for lifelong insulin injections. Among sufferers of Type 2, or adult-onset, diabetes, the reasons for insulin imbalance are more varied, and the condition can often be treated through diet and exercise alone.

Imagine the pancreas as a tree, Dr. Liddle suggested. The trunk and branches are the ducts that deliver digestive juices, the leaves the factories that make digestive enzymes, and the islet cells birds' nests scattered throughout -- in the tree but not of it.

When cancer strikes, it generally arises in the ductal tissue of the pancreas, the woody parts of our metaphoric tree, and intriguingly, they feel the part. "These tumors are rock-hard masses," said Peter Olson, an oncology researcher at the University of California, San Francisco. "They're white on dissection, very tough and fibrous."

Pancreatic cancer is almost impossible to cure. About 34,000 Americans will be diagnosed with it this year, and nearly as many will die of it. As doctors have long known, some of that lethality is positional: There is no easy way to screen the deep-set pancreas for early signs of malignancy, and by the time symptoms arise, the cancer already has spread to other organs.

Another reason for the ferocity, however, might be the nature of the tumors themselves. Most cancers are thought to spur the growth of new blood vessels to supply them with the extra oxygen and nutrients necessary for frenzied cell division, but pancreatic tumors are markedly devascularized.

"The number of blood vessels in a pancreatic tumor is 10 percent what it is in normal tissue, of the pancreas or anywhere else," said David A. Tuveson of the Cambridge Research Institute in England. The results are devastating. In the anoxic microenvironment beneath the fibrous, bloodless capsule, any malignant cells that survive become increasingly unstable and virulent, like super-roaches proliferating in the wake of a pesticide bomb. Moreover, without blood vessels, nothing can get into the tumor to kill the renegade cells, so chemotherapy is almost useless.

Reporting recently in the journal Science on results with genetically engineered mice, Dr. Tuveson and his colleagues described a new approach to treating pancreatic cancer, in which the tumors were revascularized and thus made sensitive to cancer drugs. Clinical trials are now under way to test the basic strategy in people, and with all due caveats, Dr. Tuveson said, "I am cautiously optimistic."