Tag: Dr. Norris

A group of researchers have identified a key protein complex in muscle cells that regulates the body’s response to nutrients and helps maintain healthy blood sugar levels. The researchers focused on the role of this complex, known as LRRC8, in muscle lysosomes. Lysosomes are tiny compartments inside cells that act like recycling centers. The researchers found that lysosomal LRRC8 plays a critical role in governing cellular growth and metabolism. When LRRC8 was disrupted in lab-grown muscle cells, lysosomal function was impaired, weakening how muscle cells responded to nutrients and to insulin. Furthermore, mice lacking lysosomal LRRC8 developed increased body fat, insulin resistance, and poor glucose tolerance — conditions closely linked to type 2 diabetes. This research uncovers a previously unknown connection between LRRC8 lysosomal function in muscle cells and whole-body metabolic health, opening new avenues for understanding and potentially treating metabolic diseases such as type 2 diabetes. Dr. Norris from our division was part of the research team and is a co-author on the manuscript. The peer-reviewed findings are published in Science Advances under the title: “Lysosomal LRRC8 complex impacts lysosomal pH, morphology, and systemic glucose metabolism.” The abstract is available on PubMed: https://pubmed.ncbi.nlm.nih.gov/41004571/.

Several years ago, researchers at the University of Iowa discovered that the balance between endocrine and exocrine cells in the pancreas is impacted by cystic fibrosis. The distribution of cell types in pancreases affected by cystic fibrosis suggested the emergence of a dynamic regenerative process. To better understand this possibility, the researchers teamed up with experts at the University of Colorado. The results of this collaborative work are now published in the journal iScience (PubMed link).

Cystic fibrosis is caused by the loss of CFTR function. The published work shows that when all CFTR function is lost from certain pancreatic ductal cells, these cells begin to express a protein named PDX1. This is important because PDX1 drives the development of several different components of the pancreas during organ formation. Indeed, the pancreatic ductal cells that expressed PDX1 exhibited the potential to produce several cell types, including pancreatic endocrine cells. Consistent with this, the researchers identified the presence of insulin-expressing cells within the ductal epithelium of pancreases affected by cystic fibrosis.

These findings enhance our understanding of the cellular formation of ductal versus endocrine cells in the injured pancreas and could be beneficial for future attempts at pancreatic endocrine and/or exocrine regeneration. Dr. Norris from our division was involved in the research.

What is Hemoglobin A1c? Hemoglobin A1c (HbA1c) is a blood test that measures the amount of glucose that is attached to a persons hemoglobin — the oxygen carrying protein found in red blood cells. The higher a person’s blood sugar, the more glucose that becomes attached. Because red blood cells last about 90 days, the HbA1c value reflects a person’s average blood glucose over the past 3 months. A HbA1c value over 6.4% indicates that a person has diabetes. For persons with diabetes, higher blood glucoses increase the risk of long term complications. Higher HbA1c levels are associated with increased rates of complications including diabetic eye disease, kidney disease, and neuropathy. For this reason, the American Diabetes Association recommends that most persons with diabetes have a goal of maintaining their HbA1c at less than 7%.

What is average blood glucose? In the past, HbA1c was the only widely available method to assess a person’s recent average blood glucose levels. Fortunately, technological advances over the past decades have enabled frequent testing of blood glucose using portable meters and even more powerfully using continuous glucose monitors (CGMs). CGMs are wearable devices that measure a persons approximate blood glucose every few minutes. Modern glucose meters and CGMs can report a user’s recent average blood glucoses.

Converting between average blood glucose and HbA1c A common question asked by persons with diabetes is what HbA1c is predicted by their recent average blood glucose. There are multiple online conversion calculators that address this question, allowing the user to enter an average glucose for which a predicted HbA1c is returned. However, two scientists at the University of Iowa recently identified and reported a small mathematical error in the equations commonly used by online calculators to predict HbA1c from recent average blood glucose. As a result, the erroneous online calculators do not provide optimal predictions. The two scientists were Dr. Joseph Lang from the Department of Statistics and Actuarial Science and Dr. Andrew Norris from our Division. The two then derived new equations that correct the error. Their findings and new equations have been peer reviewed and now are published as a letter in the prominent journal Diabetes Care (link to article).  Dr Norris would like to thank Dr Lang for uncovering the error and devising the approach for its correction. The hope is that the improved equations will be adopted by online calculators. In the meantime, on a positive note, many continuous glucose monitors report an estimated HbA1c that is termed “GMI” (“glucose management indicator”) and the equations used for GMI are typically correct. Drs. Norris and Lang’s letter also comments on a recently published perspective that highlights ongoing issues in the interconversion of recent average blood glucose to HbA1c. It is important to understand that neither HbA1c nor meter/monitor derived average blood glucose are perfectly accurate. Unsurprisingly, interconversions between these two measurements often do not agree. The revised equations of Dr Lang and Dr Norris will help the situation to some degree but perfect agreement is not possible in real life. Additional data and understanding of the variances that impact the relationship between these two measurements are needed.

Obesity impairs various aspects of pituitary function. Perturbations in the thyroid, growth hormone, gonadal, and adrenal axes are well documented. However, the mechanisms involved are not well understood. Furthermore, it is possible that the pituitary dysfunction induced by obesity might contribute to the medical complications of obesity. Dr. Norris, from our division, recently assisted with new research that begins to address these knowledge gaps. The investigators found that obesity in mice impaired the ability of pituitary cells to activate their cellular unfolded protein response (UPR). The UPR is a mechanism that helps protect cells against various stressors. Importantly, when the UPR was disrupted in pituitary cells by genetic manipulation, pituitary dysfunction similar to that in obesity resulted, especially in the thyroid axis. Furthermore, primary genetic UPR disruption in the pituitary resulted in UPR disruption in the liver in a manner that could contribute to fatty liver disease. The work will be published in Cell Metabolism and its abstract is available on PubMed (link). The work was conducted in the lab of Dr. Ling Yang in the F.O.E. Diabetes Research Center at the University of Iowa.