Diabetes Action Research

Diabetes Action is committed to funding promising and innovative diabetes research with a special interest in alternative, complementary, integrative, and nutritional therapies to prevent, treat, and cure diabetes and its complications.

Researchers: Please check back in 2015 for information on our next grant application cycle.

Microscope Image & Diabetes Action Research Information



Research Grants for 2015


Cure for Type 1 Diabetes

A Program for the Cure of Type 1 Diabetes Using a Generic Drug: Phase II

Denise L. Faustman, MD, PHD.

Denise L. Faustman, MD, PhD., Associate Professor
Harvard Medical School and Director Immunobiology Laboratory
Massachusetts General Hospital
Charlestown, MA

After a successful completion of the Phase I clinical trial which investigated the safety of BCG vaccination in individuals with type 1 diabetes, in 2011 Dr. Faustman’s lab launched the Phase II study which will determine what doses will be needed to make BCG a functional type 1 diabetes therapy and how frequently this treatment will be needed to maintain normal blood sugar levels. In August, 2012 publication of the full Phase I trial showed that the pancreas of long-term diabetics was able to transiently make insulin after two repeat injections of the generic vaccine, BCG. Unlike other type 1 diabetes trials which focused only on new-onset diabetics, this study is concentrating on reversing type 1 diabetes in people with longstanding disease. The current Phase II trial will provide more direction for turning BCG into a long-lasting treatment by identifying the right dose and frequency of vaccination needed to sustain a therapeutic response over several years.

Complementary / Nutrition Research


The Metabolic Basis of Obesity caused by Consumption of Sucrose-Containing Beverages


Dr. Ruth Harris

Ruth B. Harris, Ph.D., Professor
Georgia Regents Research Institute, Inc.
Augusta, GA


Consumption of sugar sweetened beverages increases risk for obesity and type 2 diabetes. We recently observed that rats given access to 30% sucrose solution rapidly develop leptin resistance. Leptin is an adipocyte-derived negative feedback signal in the control of energy balance that also inhibits adipocyte insulin sensitivity and lipogenesis. We hypothesize that leptin resistance will lift these brakes on lipid storage and the potential for increased accumulation of body fat will be exaggerated. Aim 1 will identify which aspects of the leptin signaling pathways are modified in isolated adipocytes exposed to high glucose concentrations. Aim 2 will test whether access to sucrose solution increases adipocyte insulin responsiveness and glucose uptake in rats. These Aims will provide significant new information on a mechanism linking consumption of sucrose sweetened beverages and increased adiposity and will provide support for dietary recommendations aimed at reducing obesity, metabolic syndrome, and type II diabetes.


Reversal of Diabetic Complications by Low Carbohydrate Diets


Dr. Mobbs

Charles Mobbs, Ph.D., Professor
Icahn School of Medicine at Mount Sinai
New  York, NY


A major obstacle in treating patients with diabetes is a phenomenon called metabolic memory. This phenomenon prevents complete reversal of diabetes-induced organ damage even after complete normalization of glucose levels. We have now reported that after the development of diabetic kidney damage, as indicated by elevated urinary albumin to creatine ratios and a novel panel of genes associated with diabetic kidney damage, was completely reversed by a ketogenic diet for 8 weeks. We have now also shown that neuropathy is similarly reversed by the ketogenic diet. A major question raised by these studies is whether the reversal of diabetic complications will persist after returning to a normal diet. We therefore propose to assess if reversal of diabetic complications by a ketogenic diet and a similarly low-carbohydrate but not ketogenic diet persists after returning to a normal diet.


Bypass Surgery

The Role of Intestinal Metabolic Reprogramming in Diabetes Resolution After Gastric Bypass Surgery in Human Patients

Dr. Stylopoulos

Nicholas Stylopolos, MD, Assistant Professor
Boston Children’s Hospital
Boston, MA


Roux-en-Y gastric bypass surgery (RYGBS) is considered the best treatment option for obesity-related diabetes. The mechanisms by which RYGBS improves glycemic control have not been determined. This proposal focuses on a novel mechanism that has emerged from studies in diabetic rodents by our laboratory. It was shown that after RYGBS, the intestine exhibits reprogramming of intestinal glucose metabolism and becomes a very important tissue for glucose disposal. It is speculated that reprogramming of intestinal glucose metabolism is a key mechanism that accounts for the glycemic control observed after RYGBS in human patients. This project will specifically test this hypothesis by performing a prospective longitudinal study in human patients before and after RYGBS. These studies could establish that the intestine could be a very attractive target for the treatment of diabetes and could pave the way for the development of novel non-invasive therapies for diabetes.


Gene Research

Role of Dopamine D4 Receptors in Activation of Insulin Receptors


Xiaoyan Wang, MD, Ph.D., Assistant Professor
University of Maryland Medical System
Baltimore, MD

We hypothesize that D4 dopamine receptor (D4R) positively regulates insulin sensitivity through its activation of insulin receptor B (IRB) and prevents insulin resistance in lean and obese mice. Specific Aim 1 will test the hypothesis that the molecular disruption of Drd4 gene or pharmacological D4R inhibition by antagonists decrease phosphorylation of IRB and cause insulin resistance/pre-diabetes in lean mice fed normal-fat diet. Specific Aim 2 will test the hypothesis that molecular disruption of Drd4 gene decreases phosphorylation of IRB and promotes insulin resistance/diabetes while pharmacological D4R stimulation by agonists increases phosphorylation of IRB and prevents insulin resistance/diabetes in high-fat induced obese C57BL/6J mice. The studies may allow the design of D4R mimics/agonists that can be used to prevent and treat diabetes in the future.


Beta Cell/Pancreas Research


Biofabrication of a Novel Bioink for 3D Pancreatic Organ Printing

Dr. Ozbolat

Ibrahim Ozbolat, Ph.D., Assistant. Professor
The University of Iowa
Iowa City, IA


Type 1 diabetes (T1D) is a devastating disease that develops after the auto-destruction of beta cells in the pancreas, which often leads to severe complications including blindness, limb amputations, kidney failure, nervous system diseases, and macrovascular disease, including heart disease and strokes. Up to now, it can be effectively treated with islet or cadaveric organ transplantation; however, both approaches are limited in meeting the increasing need of organ transplantation. In this project, we propose a novel scaffold-free bioink made of islet-like aggregate encapsulating connective tissues that can be used as building blocks in pancreatic organ fabrication. Successful completion of the proposed study, which aims to combine state-of-the-art 3D bioprinting and tissue engineering technologies, would be complement to our ongoing pancreatic tissue fabrication work and justify the initiation of a breakthrough development as an alternative therapy for diabetes.


Vascular Research

Acute Effect of a Mixed Meal with or without Extra-Insulin on Arterial Stiffness, a Prospective Randomized Study


Dr. Meehan

Colette Meehan, M.D., Pediatric Endocrine Fellow
University of Florida
Gainesville, FL

Blood Vessel Stiffness, specifically arterial stiffness, is an important marker of cardiovascular risk. These risks include increased atherosclerosis, high blood pressure, heart attack, and stroke. The immediate effects of high blood glucose levels on the stiffness of blood vessels in children with Type 1 diabetes (T1D) who frequently forget to take insulin with a meal (“bolusing”), are unknown. We hypothesize that an uncovered meal acutely increases arterial stiffness. Children with T1D will come into the office after fasting overnight, will be given a meal replacement drink (Boost), and randomized to either receive insulin or not receive insulin. We will then measure blood glucose level and assess their arterial stiffness. This test can be performed in the doctor’s office, is non-invasive, and provides visual feedback. We hope this project will give children with T1D the message that not bolusing insulin has an immediate and possible long term consequence.

Insulin Resistance

Role of TRBP and its Phosphorylation in Obesity-Induced Insulin Resistance and Type 2 Diabetes


Takahisa Nakamura, Ph.D., Assistant Professor of Pediatrics
Cincinnati Children’s Hospital Medical Center
Cincinnati, Ohio

With obesity in developed and developing countries on the rise, the prevalence of metabolic diseases such as fatty liver disease and type 2 diabetes has pandemically increased. Hepatic steatosis, a strong depot for triglycerides in the liver, is frequently accompanied by hepatic insulin resistance, which contributes to the development of glucose intolerance and eventually to type 2 diabetes. Growing evidence indicates that hepatic steatosis coexists with a state of metabolic inflammation in which excess nutrients trigger inflammatory and stress responses including elevated production of immune mediators and activation of stress kinase pathways. Activation of these inflammatory and stress signaling pathways underlies one of the pathologies of hepatic insulin resistance. Thus, there is a critical need to determine the pathways that initiate metabolic inflammation. In this proposal, we intend to clarify a role of TRBP-PKR protein signaling pathway in metabolic inflammation leading to hepatic steatosis, insulin resistance, and type 2 diabetes.


Exploring the Mechanism of Insulin Resistance


Janet H. Silverstein, M.D., Professor of Pediatrics & Chief, Pediatric Endocrinology
University of Florida College of Medicine
Gainesville, FL


This study is a collaborative investigation between the Univ. of Florida and The Institute for Endocrinology in Ecuador where a unique population isolate has been identified with intrauterine growth retardation (IUGR), failure of catch up growth, and absence of an adolescent growth spurt resulting in adult short stature. Although a specific cycline dependent kinase mutation appears to cause these growth problems, the exact mechanism by which this presumed limitation of beta cell reserve results in insulin resistance is unknown. This population, which all appears to have insulin resistance unrelated to obesity or other signs of metabolic syndrome, offers an opportunity to study insulin resistance in a unique phenotype without confounding factors of differing environments and metabolic comorbidities, as well as with ideal control subjects among unaffected relatives. In order to determine the relationship between overall growth inhibition and likely hyperplasia of the pancreatic islets, MRI photos of the pancreas will be performed in affected subjects and controls. These studies have the potential for identifying sites of metabolic derangement specific to insulin resistance which could have therapeutic potential.