In 2020, as part of a NIH P30 application to create a joint Minnesota-Iowa Diabetes Research Center (MIDRC), the University of Minnesota and the University of Iowa launched a Pilot and Feasibility Grant program focused on new and established investigators pursuing diabetes projects individually or in collaboration with investigators at these partner institutions. In 2021, the Institute for Diabetes, Obesity and Metabolism (IDOM) at the University of Minnesota and the Fraternal Order of Eagles Diabetes Research Center (FOEDRC) at the University of Iowa awarded two Collaborative Pilot and Feasibility Grants to support a new project led by PIs at both institutions. Each award will be $70,000 for a one year period.
The program will provide time limited collaborative seed funding to a team of investigators to generate or strengthen preliminary data that will increase their competitiveness for receiving substantial competitive extramural grant funding. These awards seek to support new and innovative research projects that will increase the understanding of fundamental mechanisms that inform the pathophysiology of diabetes and its complications or lead to translational approaches and clinical innovations. Funded Collaborative Pilot and Feasibility Grant investigators will be asked to prepare a yearly progress report and present it at the FOEDRC Frontiers in Obesity, Diabetes and Metabolism Seminar Series.
Collaborative Grant Recipients
Project Title: “Mechanisms of Dysglycemia and Development of Diabetes in Children with Acute Recurrent or Chronic Pancreatitis”
Pancreatitis is characterized by painful inflammation and scarring of the pancreas. In some children with recurrent acute or chronic pancreatitis, the damage to the pancreas is severe enough to result in diabetes mellitus (DM). However, the mechanisms that drive the development of DM in children with pancreatitis are poorly understood. In this pilot study, investigators from the University of Minnesota and University of Iowa will enroll children with pancreatitis and with or without DM from the National Institutes of Health (NIH)-funded International Study Group of Pediatric Pancreatitis: In search for a cure-2 (INSPPIRE-2) to participate in mixed meal tolerance and continuous glucose monitoring (CGM) to measure islet function and glycemic (blood sugar) control. We will assess islet function in children with pancreatitis who have normal or abnormal blood glucoses on CGM (Aim 1) and determine if risk markers usually seen in type 1 or type 2 DM also contribute to the development of DM secondary to pancreatitis (Aim 2). These pilot data will be used to support a larger multicenter study.
Project Title: “Identifying Crosstalk Between Ketone and Endocrine Signaling in the Hypothalamus”
Liver-brain crosstalk is now recognized as a fundamental driver of feeding behavior and body weight regulation, which are primary determinants of obesity and type 2 diabetes. Both nutrient fuels and hormones serve as signals from the liver to the brain. A key metabolic fuel that is produced in the liver but serves important roles in the brain is the ketone body. Ketones are produced in the liver, and are by-products of burned fat, serving as an important fuel source for the brain’s neurons. Through unclear mechanisms, ketones also modulate feeding behavior and body weight through actions upon a fundamental energy and metabolism coordinating center in the brain called the hypothalamus. In addition to ketones, the liver also produces the hormone fibroblast growth factor 21 (FGF21) which signals to hypothalamic neurons. However, nothing is known about how hypothalamic function is coordinately regulated by ketones and FGF21 together. This Pilot and Feasibility application proposes the key initial experiments that will address this critical knowledge gap. The proposed experiments forge a new collaboration between an expert in integrated ketone metabolism, metabolomics, and metabolic flux analysis (Crawford) and a co-PI who is an FGF21 signaling expert who is uniquely skilled in targeting, manipulation, and quantifications of hypothalamic neuronal signaling in vivo and ex vivo (Potthoff). The approaches described here will be the first to determine how ketones modulate hypothalamic signaling in response to FGF21, and whether their cooperative effects are dependent on ketone oxidation in neurons.