Tackling Diabetes.

This week’s theme is new therapeutic possibilities for diabetes, a disease of insulin deficiency that affects over 300 million people globally.

Aging is a prominent risk factor for both insulin resistance and impaired pancreatic insulin production—and this situation can be worsened by other comorbidities associated with aging like obesity. Thus, developing new therapeutic possibilities for improving insulin production and responsiveness is an important goal in improving quality of life during aging. Below are two recently published studies that provide promising therapeutic strategies to treat diabetes.


A New Dietary Supplement to Counteract Insulin Resistance?

By, Brandon Tavshanjian

Top: Oleic acid, a “healthy” monounsaturated fat. Bottom: A FAHFA (fatty acid ester of a hydroxy fatty acid) of oleic acid, a derivative that counteracts insulin resistance and inflammation.

Top: Oleic acid, a “healthy” monounsaturated fat.
Bottom: A FAHFA (fatty acid ester of a hydroxy fatty acid) of oleic acid, a derivative that counteracts insulin resistance and inflammation.

In a new, groundbreaking study in metabolomics (the study of how our cells transform molecules we consume) work from Barbara Kahn and Alan Saghatelian at Harvard identifies a new circulating fat derivative, fatty acid esters of hydroxy fatty acids (FAHFAs), that appears to counter type-2 diabetes (insulin resistance). This develops a long history of research that shows fatty acid metabolism (particularly hydroxy fatty acid metabolism) goes awry in aging, inflammation, and cardiovascular disease. By investigating circulating fats in type-2-diabetic mice, the groups identified this particular class of fatty acid as being 16-18-fold lower in mice with disease. Importantly, they found that these levels could be improved by feeding the mice FAHFAs, and that dietary administration dramatically improved insulin responsiveness in mice as well as markers of inflammation.

Kahn and colleagues further observed that these fatty acid esters are present in widely varying concentrations in foods, being low in vegetable sources like apples, higher in broccoli, and highest in animal products like chicken meat and egg yolk.

This work suggests a new pathway that may go awry during aging and metabolic dysfunction, as well as a convenient dietary strategy to counteract it. Further work identifying which foods present the optimal concentration of FAHFAs along with healthy fats will no doubt be quickly forthcoming.

The link to the study in the current issue of cell (subscription required): Discovery of a Class of Endogenous Mammalian Lipids with Anti-Diabetic and Anti-inflammatory Effects


Generating Functional Human Pancreatic β Cells From Stem Cells

By, Karen Ring

Human β islet cells generated from human embryonic stem cells (top) and primary human β islets (bottom) transplanted immunocompromised mice.

Human β islet cells generated from human embryonic stem cells (top) and primary human β islets (bottom) transplanted immunocompromised mice.

The main cell type affected in diabetes is the pancreatic β cell, which secretes the hormone insulin in response to blood glucose levels. Douglas Melton’s group at Harvard has figured out how to generate functional human pancreatic β islet cells from embryonic stem cells (ESCs). Unlike previous studies, the authors did not use stem cell-derived pancreatic progenitor cells for transplantation into mice. Their alternate method generated large quantities of mature β islet cell clusters from ESCs in a dish. Islet clusters secreted insulin in response to glucose at comparable levels to mature islets from the pancreas within two weeks of transplantation in mice.

This development means that patient-specific islet cells can be generated and used to better understand diabetes and improve our current knowledge of β cell function. These cells could also be used for therapeutic drug screening and cell replacement therapy for patients with type-1 diabetes (an autoimmune disorder that attacks and kills β islet cells). The ability to cure type-1 diabetes patients with easily produced functional β islets would transform current treatment strategies for diabetes. Melton’s group is currently collaborating with other labs to develop an implantation device that would protect the β cell transplants from immune system attack.

For more information, check out the published study in Cell (subscription required) and an interview of Douglas Melton in the Harvard Gazette.