Category: Diabetes

Weight cycling has been demonstrated, in humans and animal models, to increase cardiometabolic disease and disrupt glucose homeostasis. Both obesity itself and weight cycling cause adipose tissue inflammation and metabolic dysfunction. Studies show that even after weight loss, increased numbers of lipid-associated macrophages and memory T cells persist in adipose tissue and become more inflammatory […]

Diabetic cardiomyopathy (DCM), characterized by myocardial hypertrophy and fibrosis, is a severe complication of diabetes. Activation of Yes-associated protein (Yap) has been implicated in myocardial remodeling and cardiac dysfunction. This study aimed to elucidate the role and underlying molecular mechanisms of Yap in DCM. Yap expression was evaluated in mice with type 2 diabetes mellitus […]

Metabolic syndrome (MetS) is a growing health concern that increases risk for peripheral neuropathy (PN), defined by nerve degeneration and sensory dysfunction. Although lifestyle strategies, like ketogenic diet (KD) and exercise, are known to mitigate MetS, their efficacy in maintaining nerve health or reversing established PN is less clear. First, in a maintenance paradigm, we […]

An inflection point (IP) marking accelerated β-cell decline occurs ∼1–2 years before type 1 diabetes diagnosis. Precisely determining this timing could optimize clinical intervention. We developed machine learning models to predict proximity to the inferred metabolic IP using oral glucose tolerance test (OGTT) data from islet autoantibody-positive individuals in the TrialNet Pathway to Prevention study. […]

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 […]

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 […]

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 […]

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 […]

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 […]

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 […]