Researchers Find Striking Differences Between Human and Animal Insulin-Producing Islet Cells

Images of mouse and human islets
Comparing microscopic images of mouse (A) and human (B) islets show major differences in the internal composition of these cell clusters. Each islet is made up of four types of cells that interact to regulate blood sugar levels. In the mouse (A), the insulin containing beta cells (red) are located together in the center of the islet with the other endocrine cells surrounding the beta cell core. In contrast, human beta cells (B) are seen throughout the islet and closely associated with the other cells. This is unique to human islets.

Miami, FL (February, 2006) — Diabetes researchers have discovered that the internal structure of human insulin-producing islet cells is dramatically different than the well studied islets in rodents – a striking finding that will impact the way research is conducted if it is to benefit people living with diabetes.

For more than three decades, scientists have based their knowledge of the cytoarchitecture, or cell structure, of islets on the rodent model. The structure of human islets has been poorly understood, but researchers assumed the cells had a similar make up.

Now, scientists from the Diabetes Research Institute (DRI) at the University of Miami Miller School of Medicine have shown that the composition of a human islet is so different than that of the rodent model, it is no longer relevant for human studies. 
Their results are published in the Proceedings of the National Academy of Science.

“Our major finding is that human pancreatic islets have a unique architecture, and work differently than rodent islets,” said Per-Olof Berggren, adjunct professor at the Diabetes Research Institute and professor at the Rolf Luft Center for Diabetes Research at Karolinska Institutet in Stockholm, Sweden. “We can no longer rely on studies in mice and rats. It is now imperative that we focus on human islets. At the end of the day, it is the only way to understand how they function.”

The islets of Langerhans, located in the pancreas, regulate blood glucose levels. Islet cells consist of four types of secretory cells: insulin containing beta cells, glucagon containing alpha cells, somatostatin containing delta cells, and PP cells, which contain pancreatic polypeptide.

The investigators, led by Drs. Berggren and Alejandro Caicedo, compared the cellular composition of human islets to those of other mammalian species. In rodents, a layer of alpha, delta and PP cells cluster around a core of beta cells to form the islet structure. In humans however, all four cell types within the islet are mixed together, resulting in the beta cells having direct contact with the other cells.

The research team also discovered that the beta cells were the most abundant cell type in the islets of all species. However, the proportion of beta cells was higher in the mouse islets than in the human cells, 77 percent vs. 55 percent. Additionally, 71 percent of mouse beta cells “associated” with their neighboring beta cells, while only 29 percent of human beta cells did so.

Scientists think this construct affects the way all of the cells “talk” to each other, which could have a major impact on how islets respond to glucose and their ability to survive.

The cells’ survival is a key factor for successful islet transplantation, considered the most promising method for curing diabetes. During the procedure, the islets are first separated from a donor pancreas and then infused into the patient, where they begin to produce insulin.

Researchers have shown that only the healthiest islets will be able to produce enough insulin to regulate blood sugars, as well as survive long term. For this reason, they have focused on developing tests that can predict the health and viability of an islet before it is transplanted into a patient.

“This study was the first step in understanding the structure of the human islet. Now we need to better understand how human islets respond to glucose and how they secrete insulin,” said Dr. Caicedo, research assistant professor at the Diabetes Research Institute. “As we further our knowledge of human islet biology, we will be able to improve our methods to assess islet quality and determine whether to transplant them or not, “This will be very important if we are going to establish islet transplantation as a standard therapy for patients with type 1 diabetes.”

While the study shows that the next step in the research process must be focused on human cells, scientists maintain that the use of rodent models continues to be relevant in “bench to bedside” or translational research.

“The results of this study do not decrease the value of basic science and small animal based research,” explained Dr. Camillo Ricordi, scientific director of the Diabetes Research Institute and Stacy Joy Goodman Professor of Surgery. “However, it does underscore the critical importance of translational research, that is, to determine if observations obtained in rodent studies are relevant to patients. Using human tissues and pre-clinical model systems, we can transfer any new pertinent finding toward new treatments for patients in the fastest, most efficient and safest way possible.”

The Diabetes Research Institute at the University of Miami is a recognized world leader in cure-focused research. Pioneering new technologies in islet transplantation and other cellular therapies since the early 1970’s, the DRI has successfully reversed diabetes in patients involved in ongoing clinical trials. The most comprehensive diabetes research facility of its kind, the DRI conducts a broad range of scientific programs focused on gene therapy, pancreatic stem cell development, molecular biology and transplant immunology, among others, to speed the most promising findings from the lab to the patient.

For the millions of families affected by diabetes who are looking to the world of science for answers, the DRI is the best hope for a cure.


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