New FOEDRC study reveals how too much fat in insulin producing cells in the pancrease may lead to type 2 diabetes
Pancreatic beta cells are only cells that can make insulin in humans. In type 2 diabetes, pancreatic beta cells are damaged and cannot make sufficient insulin to keep blood glucose levels normal. As overnutrition and obesity is a well-known risk factor for type 2 diabetes, it is important to find a way to protect beta cells from over nutrition.
In a recently published study in the scientific journal JCI Insight, led by Dr. Yumi Imai, Associate Professor of Internal Medicine and member of the FOEDRC, her laboratory has discovered that a protein known as Perilipin 2 plays an important role in protecting beta cells under nutritional challenge. Perilipin 2, regulates an organelle called lipid droplets that prevent toxic lipids from being released from these lipid droplets. When these lipids or fats are released into the cell, they will damage beta cells and reduce their ability to produce insulin. Diabetes increases the number of lipid droplets that accumulate in beta cells in the pancreas. Therefore, it is very important under these circumstances that more perilipin is available to prevent these lipid droplets from releasing toxic lipids. Their study showed that lowering the levels of perilipin 2 led to increased injury of beta cells and reduced insulin secretion. The study was performed through collaboration with other members of FOEDRC including, Drs. James Ankrum, Brian O’Neill, Samuel Stephens, William Sivitz, and Stefan Strack. Each of these researchers brought specific expertise to the project. For example, they visualized a previously unrecognized connection between perilipin 2 and another organelle the mitochondria (that makes energy for insulin release), using sophisticated techniques and in human islet cells. This study increases our understanding of why beta cells fail during states of overnutrition and identified a new target Perilipin, whose levels if increased can protect beta cells and reduce the risk of developing type 2 diabetes.
FOEDRC research discover a new brain pathway that regulates body weight gain that is independent of the complications of obesity such as diabetes and high blood pressure
Obesity has reached epidemic proportions in the US and around the world. This is a problem because being obese increases the likelihood of developing serious medical problems such as type 2 diabetes, high blood pressure and cardiovascular diseases such as heart attacks and heart failure. Obesity also increases the risks of complications from COVID-19 infections. We still do not understand all of the reasons why obesity develops and why some people develop complications and others do not. In work recently published in the Journal Molecular Metabolism, FOEDRC member Dr. Kamal Rahmouni, PhD, professor of Neuroscience, Pharmacology, and Internal Medicine, in collaboration with FOEDRC colleagues at the University of Iowa, identified a protein complex, called the BBSome. These are present in neurons (nerve cells) in a part of the brain called the hypothalamus. The hypothalamus is a small area in the brain that determines whether the calories derived from the food we eat is burned or stored in the form of fat. The BBsome in these nerve cells regulate body fat and development of obesity. Dr. Rahmouni’s team found when the BBSome was removed from neurons of the hypothalamus, animals progressively increased body fat and weight resulting in obesity. This is due to inability of the hypothalamus to properly send signals to peripheral tissues that burn calories. As a result, these animals had lower metabolic rates as indicated by reduced energy expenditure. Because of this, their bodies were burning less calories than they should. Therefore, most of the ingested calories were directed to the fat tissues for storage, which increased the mass of fat tissue leading to obesity. These findings indicate that defects in the BBSome could be a potential cause of obesity. Very interestingly, the obesity that resulted from absence of the BBSome in the hypothalamus did not lead to diabetes, insulin resistance or high blood pressure. These findings are very similar to what is seen in a small subset of obese humans, referred to as “healthy obese,” who do not develop type 2 diabetes and cardiovascular diseases. The Rahmouni group is now conducting follow up studies to further understand what confers this remarkable protection against obesity-related conditions. Answering this question will reveal how metabolic and cardiovascular disease develop in obesity and may lead to more specific ways to treat these complications, particularly in individuals who struggle to lose weight.
Rouabhi M, Guo DF, Morgan DA, Zhu Z, López M, Zingman L, Grobe JL, Rahmouni K.. BBSome Ablation in SF1 Neurons Causes Obesity without the Comorbidities. Mol Metab. 2021 Mar 12:101211. doi: 10.1016/j.molmet.2021.101211. Epub ahead of print. PMID: 33722691.
FOE Investigators invited to educate the diabetes research community on new hormones from the liver that regulate metabolism
FOEDRC member Matthew Potthoff, Ph.D., Associate Professor of Neuroscience and Pharmacology, and graduate student Sharon Jensen-Cody recently wrote a review article entitled: “Hepatokines and metabolism: Deciphering communication from the liver” that was published in the Journal Molecular Metabolism. This article was featured on the cover of the February issue of the Journal, that increased the visibility of their work. In that article Drs. Potthoff and Jensen-Cody note that the liver plays an important role in the regulation of the body’s energy metabolism. It is able to sense when nutrients are present in excess or are deficient. In response to these nutritional changes, the liver will release hormones that will instruct other tissues in the body how to respond. This means that the liver is now recognized as an endocrine organ (gland) that secretes hormones, which are now known as hepatokines. These liver-derived factors can signal to and communicate with distant tissues. In this review, Potthoff’s lab describe the growing list of hepatokines and their role in metabolic control. They also examine how each of these hepatokines function at the cellular and molecular level. They also discuss their potential to be used as as therapies for metabolic disorders such as diabetes and obesity. Dr. Potthoff’s laboratory in the FOEDRC has made major advances to this area of research, and his influence in this area is exemplified in this article.
FOEDRC Pioneering the Way
This month, the Spring 2021 issue of the Iowa Magazine devoted its cover and featured the University of Iowa Fraternal Order of Eagles Diabetes Research Center (FOEDRC). The heartwarming article shares real life testimonies of diabetic individuals, cared for at the University of Iowa and the impact of diabetes on their daily life. The desire for relief is real and certainly not lost on physicians and scientists at the FOEDRC. The Center’s mission is to improve the lives of individuals with the disease and find a cure. Every day dedicated FOEDRC scientists conduct a wide range of research projects to improve and benefit the lives of many.
In addition to featuring the work of specific FOEDRC members and highlighting the commitment of the FOEDRC to training the next generation of diabetes researchers, the article reminds us of the generous $25 million gift from the Fraternal Order of Eagles. Without the generosity of the Eagles, we would not have been able to make these wonderful strides in diabetes research. Thank you.
Below is the link to the Iowa Magazine article, I know you will enjoy reading it as much as I did.