Angiotensin II (AngII) activation, a key driver of diabetes pathogenesis and associated complications, induces kidney injury by promoting oxidative stress and inflammation. Ferroptosis is an iron-dependent regulated cell death, playing a crucial role in kidney injury. This study aimed to explore the contribution of ferroptosis to AngII-induced kidney injury and its regulatory mechanisms. Our findings […]
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Long Duration of Type 2 Diabetes Drives Erythrocyte-Induced Vascular Endothelial Dysfunction: A Link to miRNA-210-3p
Type 2 diabetes increases cardiovascular risk, with endothelial dysfunction playing a key role. Prolonged disease duration exacerbates cardiovascular risk, but the underlying mechanisms remain unclear. We previously demonstrated that red blood cells (RBCs) from individuals with type 2 diabetes impair endothelial function via reduced miRNA (miR)-210-3p. We investigated whether disease duration influences RBC-induced endothelial dysfunction […]
Read MoreParacrine Hormonal Signals From Islet α-Cells Regulate Microtubule Dynamics in β-Cells to Promote Insulin Secretion in Mouse and Human Islets
The microtubule network in β-cells attenuates insulin secretion by pulling insulin secretory granules away from the plasma membrane. Thus, high-glucose–induced microtubule remodeling is required for robust glucose-stimulated insulin secretion. We now demonstrate that hormones secreted by α-cells regulate microtubule dynamics in β-cells through receptors for glucagon (GcgR) and glucagon-like peptide 1 (GLP-1R). Activation of GcgR […]
Read MoreGLP-1, Pancreatic β-Cells, and Insulin Secretion: What We Know and Where We Need to Go
GLP-1 receptor agonists have emerged as key pharmacological tools in the treatment of type 2 diabetes and obesity. While their anorexigenic effects are well characterized, the mechanisms by which GLP-1 modulates pancreatic β-cell function remain only partially understood. In this article, we argue that GLP-1 receptor agonists should be viewed as integrative regulators of β-cell […]
Read MoreAmino Acid Sensing by the α-Cell Mitochondrial Phosphoenolpyruvate Cycle Regulates Intracellular Ca 2+ Levels Without Affecting Glucagon Secretion
Pancreatic islet α-cells are increasingly recognized as amino acid sensors for the organism. Building on our prior work in β-cells, we sought to determine whether the mitochondrial phosphoenolpyruvate (PEP) cycle is involved in α-cell amino acid sensing. Three different methods were used to probe the PEP cycle, including pyruvate kinase activators (TEPP-46), and mice with […]
Read MoreIdentifying Insulin Autoantibodies With Differential Risk in Type 1 Diabetes With a Novel Bridging ELISA
Insulin autoantibodies (IAAs) are commonly measured by radiobinding assays (RBAs), which detect both high- and low-affinity binding. Improved assays that preferentially detect high-affinity IAA are likely to provide greater specificity and thereby increase the diagnostic accuracy of IAA for early-stage type 1 diabetes (T1D). This study aimed to develop and validate a novel bridging ELISA […]
Read MoreDownregulation of Hepatic PPA1 Protects Against Obesity by Elevating FGF21 Production via eIF2α Phosphorylation
Chronic overnutrition promotes excessive hepatic triglyceride accumulation, subsequently leading to insulin resistance and systemic metabolic dysfunction. Inorganic pyrophosphatase 1 (PPA1), an enzyme that hydrolyzes inorganic pyrophosphate, plays a key role in driving synthetic biochemical reactions. Here, we identified PPA1 as a novel regulator of systemic energy expenditure that functions by controlling hepatic production of fibroblast […]
Read MoreIntegrating SMRT and Bulk RNA Sequencing With Metabolic Phenotyping to Examine Reduced Skeletal Muscle Mitochondrial Respiration in Type 2 Diabetes
Recent advances in RNA sequencing (RNA-seq) techniques allow the identification of tissue-specific alternative splicing and can thereby provide new insights into molecular mechanisms of energy metabolism. Full-length transcriptomics based on single-molecule real-time sequencing (SMRT-seq) enable precise detection of isoforms with 99% accuracy in an unbiased manner. In this proof-of-concept study, we integrated SMRT-seq, bulk RNA-seq, […]
Read MorePhase I Clinical Trial of Islet Antigen–Specific Plasmid Coexpressing Tolerogenic Proteins Demonstrates Safety in Adults With Type 1 Diabetes
There is significant interest in antigen-specific approaches to delaying type 1 diabetes in preclinical stages and supporting tolerance after diagnosis. We conducted a phase I trial of a nonintegrating DNA plasmid constructed to secrete the type 1 diabetes antigen preproinsulin (PPI) and the immune modulatory cytokines transforming growth factor-β1 (TGF-β1), interleukin-10 (IL-10), and IL-2. In […]
Read MoreDiabetes Spotlight: Martin Myers, MD, PhD—Understanding Metabolism and Glucose Through Neural Networks
“We moved a lot, but I did most of my growing up outside Iowa City, Iowa,” Martin Myers says. His father was a physician, but his family lived on a farm that grew corn and soybeans. They had horses. He and his brother raised sheep. “We got up to no good,” he says. “Banging around […]
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