Search Medical Journals & Research Articles

Neural Regulation of Blood Glucose in Acute Stress: A Report on Research Supported by Pathway to Stop Diabetes

There is significant evidence that acute stress, a challenge to an organism’s homeostasis, has dramatic effects on metabolic control. Acute stress impairs blood glucose control in people with both type 1 and type 2 diabetes. In addition, growing evidence suggests that metabolic responses to stress in people without diabetes may be a crucial determinant of health. Acute dysregulation of blood glucose in the hospital setting, including both hyper- and hypoglycemia, predicts short- and long-term morbidity and mortality in patients with critical illnesses. Animal studies indicate that exposure to physiological and psychological stressors activates a highly conserved network of neural circuits that ultimately coordinate the functions of multiple organs to increase blood glucose. In this article, we provide an overview of the neural populations and circuits that increase blood glucose in response to acute stress, including our research funded by the American Diabetes Association Pathway to Stop Diabetes program, highlighting the impacts on clinical outcomes and opportunities for the development of therapies for diabetes. This article is part of a series of perspectives that report on research funded by the American Diabetes Association Pathway to Stop Diabetes program. Article Highlights Internal and external stressors rapidly increase blood glucose, a highly conserved metabolic response. Multiple stress-modulated neural populations in the brain stem, hypothalamus, and forebrain contribute to regulation of the hypothalamo-pituitary-adrenal axis and sympathetic nervous system to elicit hyperglycemia. Exaggerated or diminished glucose responses to acute stress are associated with increased risk of type 2 diabetes and poor health outcomes. A greater understanding of the neural circuitry contributing to stress hyperglycemia and how these circuits are disrupted has the potential to provide new approaches to improve glycemic control.

Publisher’s Note

Publisher’s Note. Simon A. Hawley, Rebecca J. Ford, Brennan K. Smith, Graeme J. Gowans, Sarah J. Mancini, Ryan D. Pitt, Emily A. Day, Ian P. Salt, Gregory R. Steinberg, and D. Grahame Hardie. The Na+/Glucose Cotransporter Inhibitor Canagliflozin Activates AMPK by Inhibiting Mitochondrial Function and Increasing Cellular AMP Levels. Diabetes 2016;65:2784–2794. https://doi.org/10.2337/db16-0058

Diabetes Spotlight: Susan Bailey Gurley, MD, PhD—Charting Hypertension and Diabetic Nephropathy Through Mouse Models

A key question for scientists as they raced to understand SARS-CoV-2: what was the human entry point for the virus that causes COVID-19? The answer, angiotensin-converting enzyme 2 (ACE2), was a protein Susan Gurley had studied for decades, not as a virologist but as a nephrologist. “I still study ACE2 in the context of kidney function,” Gurley says. “Hypertension. Blood pressure regulation. But most people who study ACE2 are interested in its connection to COVID.”

Dickkopf 3 in Urine: A Help for Prioritizing Management of Kidney Disease in Type 2 Diabetes

It has never been a bigger problem than now: it is estimated that more than 800 million people have chronic kidney disease (CKD) and diabetes is the leading cause of CKD, all projections say that prevalence of both type 2 diabetes and CKD will increase in the coming years, and CKD is expected to become the fifth most common cause of death.

ABCC8 Missense Variants and Disease: Loss or Gain? This Is the Question

Establishing the relevance of a genetic variant in the causality of a given disease is crucial. Clinical molecular geneticists use a variety of tools including mode of inheritance, segregation in the family, penetrance, and determination of the variant as loss of function (LOF) or gain of function (GOF). However, this approach to determining how a variant causes disease comes into question when variants appear to cause both LOF and GOF at different times in a patient’s lifetime (hyperinsulinism [HI] at birth due to LOF and diabetes either at birth or in later years due to GOF). This, in turn, impacts the mechanism(s) of disease and ultimately the diverse phenotypes that LOF or GOF in the same gene can determine. In genes that control insulin secretion, there is the added complexity that HI leads to premature apoptosis of β-cells potentially causing premature β-cell failure and diabetes, thus mimicking a change from LOF to GOF ( 1 ). In their article in this issue of Diabetes, Scala et al. ( 2 ) describe a series of patients presenting with a phenotype consistent with maturity-onset diabetes of the young (MODY) and the surprising finding of LOF in ABCC8 variants and propose that there are two distinct forms of K ATP channel–associated MODY. Their article, and the questions they raise, indicates that for the general endocrinologist/diabetologist interpretation of genetic tests requires a far more complex understanding than simple Mendelian inheritance. This complexity, specifically in ABCC8, suggests the need for consulting with geneticists and experts in the specific disease and genes and that, for laboratories reporting genetic testing, much more careful and specific interpretation needs to be provided to the ordering physician.

Engineered enzyme turns formaldehyde pollutant into key pharmaceutical building block

Formaldehyde is a common chemical used in various industries as a disinfectant, resin precursor, and synthetic intermediate. It is volatile, highly toxic, and a key environmental pollutant with genotoxic and carcinogenic effects, harming both human health and the environment. Therefore, there is an urgent need to come up with useful strategies to convert formaldehyde into non-toxic value-added products, ensuring environmental protection as well as chemical sustainability.

Eifel volcanoes mapped in detail: Surprising new insights from Germany's largest seismological experiment

Several hundred volcanoes lie dormant beneath the Eifel in western Germany. They are typical examples of what is known as distributed volcanic fields. To better understand their formation and activity, researchers from the GFZ Helmholtz Center for Geosciences and partner institutions conducted Germany's largest seismological volcano experiment in this region between September 2022 and August 2023.

Expansion of invasive Chinese hwamei into alpine habitats in Japan: First record of songs

Researchers at University of Tsukuba have, for the first time, recorded the songs of the Chinese hwamei Garrulax canorus (designated as an invasive alien species) in the alpine zone of Mt. Kisokoma in the Central Alps (approximately 2,770 m above sea level). These songs, produced by males during the breeding season, serve to establish territories and attract females. This finding, published in Bird Research, raises concerns that the breeding range of Chinese hwamei may be expanding from lowland habitats into the alpine zone.

Potentially toxic elements in bananas grown in the Mariana disaster region exceed United Nations limits

Scientists specializing in soil geochemistry, environmental engineering, and health affiliated with the University of São Paulo (USP) and the Federal University of Espírito Santo (UFES) in Brazil and the University of Santiago de Compostela in Spain assessed the risks of consuming bananas, cassava, and the pulp of cocoa grown in soils impacted by iron mining waste in the Doce River estuary in Linhares in the Brazilian state of Espírito Santo. The region has received the material since the Fundão tailings dam collapsed in the neighboring state of Minas Gerais in November 2015.

How ancient viral DNA shapes early embryonic development

A new study from the MRC Laboratory of Medical Sciences (LMS) in London, UK reveals how ancient viral DNA once written off as "junk" plays a crucial role in the earliest moments of life. The research, published in Science Advances, begins to untangle the role of an ancient viral DNA element called MERVL in mouse embryonic development and provides new insights into a human muscle wasting disease.

How mountain building and climate change have shaped alpine biodiversity over 30 million years

In a study published in Science Advances on December 19, researchers from Xishuangbanna Tropical Botanical Garden (XTBG) of the Chinese Academy of Sciences, along with collaborators from international institutions, explored the impact of mountain building and climate cooling over 30 million years across five major mountain systems in the Northern Hemisphere and revealed that these processes are key drivers of the rich plant diversity found in Earth's alpine biome.

A molecular gatekeeper that controls protein synthesis

Researchers at ETH Zurich recently explained the role of a molecular complex that orchestrates the production of proteins in our cells. They now show that this complex also controls the processing of proteins that compact DNA. These new insights could form the basis for new approaches in cancer treatment, but they also critically extend the current understanding of protein biosynthesis.

Wildfires reshape forest soils for decades, with recovery varying by climate

Wildfires may disappear from the landscape within weeks, but their hidden effects on the soil can persist for decades. An international research team led by the University of Göttingen, together with partners in Tübingen, Berlin and Chile, has shown how wildfires in humid temperate rainforests and Mediterranean woodlands of central Chile lead to very different pathways of soil recovery and ecosystem resilience. The study shows that soil structure and nutrients continue to change for more than a decade after a fire. The results are published in the journal Catena.

Lapland's next hotspot after Santa? Torne Valley seeks sustainable tourism

In Finland, Lapland's tourism has grown so rapidly that Rovaniemi, the region's capital and number‑one destination, where Santa Claus has his office, is already operating at full capacity. There is very little room left to welcome more tourists to the city located in the Arctic Circle. Attention has therefore turned to the next rising destinations in Lapland—one of which has been found along the Swedish border in Torne Valley, an area with a long and rich but largely forgotten tourism history.

Imaging Hypoxia in the Diabetic Retina: A Potential Early-Detection Imaging Biomarker Before Detectable Retinopathy in Diabetes

Current imaging technologies cannot detect diabetic retinopathy until there has been significant permanent damage to patients’ vision. We hypothesized that hyperglycemia causes retinal hypoxia, and hypoxia may lead to apoptosis of retinal cells. We performed experiments using a mouse model of streptozotocin (STZ)-induced diabetes to investigate the role of hyperglycemia in diabetic eye disease. Our experimental results indicate that diabetic retinas are significantly hypoxic compared with nondiabetic controls. Retinal hypoxia can be detected using HYPOX-4, an early-detection imaging probe, potentially before any detectable changes in the diabetic retina. In the early stages of diabetes, we did not observe any detectable changes in electroretinography response, vascular permeability in fluorescein angiography, or retinal thickness in optical coherence tomographic imaging. In addition, increased HYPOX-4 fluorescence in the diabetic retina was not associated with focal ischemia; rather, increased levels of HYPOX-4 fluorescence were observed throughout the entire diabetic retina. Moreover, hypoxia profiles in STZ-induced diabetic retinas were colocalized with TUNEL-positive apoptotic cells. To confirm the role of hyperglycemia in the diabetic retina, human retinal cells were treated under hyperglycemic conditions, and hypoxia was monitored using the pimonidazole-adduct immunostaining method. Surprisingly, retinal cells became hypoxic under hyperglycemic conditions within the first few hours. We conclude that the diabetic retina becomes hypoxic as a result of hyperglycemia in the early stage of diabetes, which could lead to the degeneration of retinal cells at later stages of the disease. In addition, HYPOX-4 could be used as a powerful early diagnostic imaging method to detect retinal hypoxia in the diabetic retina before any detectable retinopathy. ARTICLE HIGHLIGHTS Hyperglycemia causes retinal hypoxia. Hypoxia may lead to apoptosis of retinal cells. Retinal hypoxia can be detected before any detectable changes in the diabetic retina. HYPOX-4 is a powerful early diagnostic imaging method to detect hypoxia in the diabetic retinas of living patients.