The naturally occurring peptide, liver-expressed antimicrobial peptide 2 (LEAP2), has gained interest as a ghrelin receptor antagonist. We previously reported reduced food intake and plasma glucose–lowering effects of LEAP2 infusion in lean healthy men; however, the effects of this competitive antagonist and inverse agonist of the ghrelin receptor in men with obesity have not been […]
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Inhibition of miR-181c-5p Rescues Diabetes-Impaired Angiogenesis in Ischemia and Wound Healing
Diabetes-related vascular complications are characterized by impaired ischemia-driven angiogenesis and delayed wound healing. MicroRNAs (miRNAs) are emerging as powerful targets for multifaceted diseases. We previously identified that miRNA-181c-5p has anti-angiogenic properties, but its role in diabetes is unknown. In a hindlimb ischemia model, streptozotocin-rendered diabetic mice treated with an miRNA-181c-5p inhibitor (anti–miR-181c-5p) exhibited improved blood […]
Read MoreThe Downregulation of Type 1 Diabetes Susceptibility Gene PGM1 Induces Metabolic Imbalance and Stress in Pancreatic β-Cells
Phosphoglucomutase 1 (PGM1) is a type 1 diabetes susceptibility gene that potentially plays a key role in regulating central carbon metabolism in β-cells. Previous work suggested that β-cell PGM1 transcription is lowered after coxsackievirus B4 infection. Thus, we hypothesized that decreased PGM1 levels disrupt β-cell metabolic homeostasis and result in β-cell fragility and type 1 […]
Read MoreA Self-Reinforcing LGR5–Wnt/β-Catenin–Nedd4L Circuit Drives Fibrotic Progression in Diabetic Kidney Disease
Diabetic kidney disease (DKD) is a major cause of end-stage renal failure, driven by tubulointerstitial fibrosis. While persistent Wnt/β-catenin signaling promotes fibrosis, its sustained activation mechanism was unclear. This study, using DKD patient samples, db/db mice, and Nedd4L knockout models combined with molecular techniques, identified a key pathogenic circuit. LGR5, upregulated in diabetic kidneys, amplifies […]
Read MoreGut-Derived FGF15 Modulates Lean Mass, Bone, and Bile Acid Responses to Weight Loss
Dietary, surgical, and pharmacological methods can effectively reduce body weight; however, rapid weight loss can also be accompanied by a loss of lean mass. Previously, we found that intestinal fibroblast growth factor 15 (FGF15; mouse ortholog of human FGF19) protects against lean mass loss after sleeve gastrectomy in mice and that circulating FGF19 predicts lean […]
Read MoreHuman iPSC-Based Modeling Identifies Epigenetic Regulation at the KCNQ1 Locus During Early Islet Development That Contributes to Lower β-Cell Mass
The strongest type 2 diabetes signal in Indigenous Americans from Arizona is in intron 15 of KCNQ1. We previously identified a functional region in this intron that contained four type 2 diabetes–associated single nucleotide polymorphisms (SNPs) (rs2299620, rs2237896, rs2237897, and rs74046911) and demonstrated functionality of this fragment using Indigenous American induced pluripotent stem cell (iPSC)-derived […]
Read MoreDifferent Metabolic Responses to Long-term Weight Loss After Lifestyle Intervention Among Type 2 Diabetes Risk Clusters: Results From the TULIP Study
We previously identified six clusters of people at different risks of type 2 diabetes and/or comorbidities, of which cluster 3 (β-cell deficient) and 5 (older age, higher BMI, severe insulin resistance) had a high risk of progression to diabetes. We have now investigated whether cluster 3 and 5 individuals differed from those of the other […]
Read MoreCooperative Action of Cathepsin K Inhibitor and hUMSC-EVs in Attenuating Ferroptosis Sensitivity for Superior Diabetic Wound Healing
Refractory chronic diabetic wounds severely threaten patient survival; however, current treatments do not adequately promote healing. Cathepsin K (CTSK), a collagen-degrading protease upregulated in early diabetic wounds, presents a potential therapeutic target, and human umbilical cord mesenchymal stem cell–derived extracellular vesicles (hUMSC-EVs) show promise in regeneration but are associated with challenges related to production yield […]
Read MoreDiabetes Spotlight: Jonathan Campbell, PhD—Understanding Incretins Through α-Cell–to–β-Cell Communication and Receptor Signaling Pathways
“It was always sports,” Jonathan Campbell says, describing his childhood. He grew up in Toronto, where his father worked as a hydrogeologist and his mother as a grade school teacher. His initial interest was soccer, but by high school his focus had shifted entirely to basketball. “I spent a lot of time on a basketball […]
Read MoreBeyond Blood Sugar: Exploring the Contribution of Metabolic Syndrome to Peripheral Neuropathy
American Neuromuscular Foundation10.13039/100025799Mid-career Research Grant Source link
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