Author: sugaradmin

Finding ways to increase β-cell mass is a key goal of diabetes research. During elevated insulin demand, β-cells turn on endoplasmic reticulum (ER) stress response pathways, and some β-cells enter the cell cycle. ER stress response protein activating transcription factor 6 (ATF6α) induces β-cell proliferation, but only in high glucose. The mechanism by which ATF6α […]

Activated neutrophils contribute to retinal endothelial cell (EC) death and capillary degeneration associated with early diabetic retinopathy (DR), a major vision-threatening complication of diabetes. However, the factors and mechanisms driving neutrophil activation and cytotoxicity in diabetes remain insufficiently understood. Here, we show that lysyl oxidase (LOX), a matrix cross-linking and stiffening enzyme that increases retinal […]

Type 1 diabetes (T1D) is an autoimmune disease characterized by progressive stages culminating in T-cell–mediated destruction of the β-cells at the islets of Langerhans. The immune mechanisms that initiate T1D are not fully resolved but likely involve an interaction between proinflammatory antigen-presenting cells (APCs) and autoreactive T cells that initiate immune infiltration and activation. Previous […]

Glucokinase (GK) catalyzes the key regulatory step in glucose-stimulated insulin secretion (GSIS). Correspondingly, hetero- and homozygous mutations in human GCK cause maturity-onset diabetes of the young (GCK-MODY) and permanent neonatal diabetes mellitus, respectively. To explore the possible utility of GK activators (GKAs) and of glucagon-like peptide 1 (GLP-1) receptor agonists in these diseases, we have […]

Diabetic cardiomyopathy (DbCM) is characterized by metabolic remodeling and energetic stress independent of coronary artery disease. Increased reliance on fatty acid and ketone body metabolism has been observed in DbCM, but the regulatory mechanisms linking altered substrate use to myocardial dysfunction remain poorly understood. In particular, lysine β-hydroxybutyrate (Kbhb), a ketone body–derived, posttranslational modification, has […]

miRNAs are key regulators of metabolic homeostasis, yet their role in obesity-associated dysfunction remains incompletely understood. Here, we identify miR-432 as a driver of systemic metabolic dysregulation. Serum miRNA profiling revealed a positive correlation between miR-432 expression and obesity/type 2 diabetes mellitus. Functionally, adipose-specific miR-432 exacerbated high-fat diet–induced obesity and insulin resistance. Similarly, hepatic-specific miR-432 […]

Type 1 diabetes is a progressive autoimmune disease characterized by the selective destruction of insulin-producing β-cells by CD8+ T cells. Although the mechanisms of antigen-specific β-cell killing are well established, the broader consequences of this targeted destruction on neighboring β-cells that escape direct T-cell receptor (TCR)–mediated attack remain poorly understood. Here, we developed a coculture […]

Obstructive sleep apnea (OSA) is a common condition strongly linked to increased cardiovascular risk and poor glycemic control. Little is known about OSA, cardiovascular risk, and glycemia in maturity-onset diabetes of the young (MODY), an inherited form of diabetes, which is different than both type 1 and type 2 diabetes. We assessed OSA, resting heart […]

Polygenic scores strongly predict type 1 diabetes risk, but most scores were developed in European-ancestry populations. In this study, we leveraged recent multiancestry genome-wide association studies to create a Type 1 Diabetes Multi-Ancestry Polygenic Score (T1D MAPS). We trained the score in the Mass General Brigham (MGB) Biobank (372 individuals with type 1 diabetes) and […]

Preclinical studies show that dietary or central administration of monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) can reduce food intake, enhance energy expenditure, and attenuate hypothalamic inflammation (HI), whereas saturated fatty acids (SFAs) promote weight gain, HI, and neuronal injury. However, whether hypothalamic exposure to different fatty acids similarly influences HI and body […]