Month: June 2026

Attrition of islet function is observed over time following total pancreatectomy with islet autotransplantation (TPIAT). Metabolic stress on a suboptimal islet mass is a suspected, but unconfirmed, contributor. We measured proinsulin–to–C-peptide (PI:C) ratios as an indicator of β-cell stress in TPIAT recipients >5 years post-TPIAT. Individuals ≥16 years old with TPIAT 5–20 years prior underwent […]

MicroRNAs (miRNAs) are small RNAs that posttranscriptionally repress gene expression of their target mRNAs. miRNA discovery dates to 1993, when Ambros and Ruvkun identified them in nematodes. More than two decades later, their pioneering research was recognized with the Nobel Prize in Medicine, a fitting acknowledgment of the profound impact these tiny molecules exert on […]

Neuropathic pain associated with diabetic peripheral neuropathy (DPN) is a common and hard-to-treat complication of diabetes. Ion channels of plasma membrane are major mechanisms and targets for DPN pain. This study explores the role of a major lysosomal ion channel, TRPML1, in DPN pain. Mouse models of DPN pain and TRPML1 knockout were combined with […]

The salutary effects of physical exercise in mitigating metabolic disorders, particularly type 2 diabetes, are well recognized. Several studies have demonstrated that endurance training boosts the production of exercise-induced myokines, which are pivotal for interorgan communication enhancing insulin sensitivity. However, several challenges, including an incomplete understanding of underlying molecular mechanisms, hinder their therapeutic application. Here, […]

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) ameliorate hyperglycemia by directly stimulating insulin secretion from the pancreas. In contrast, the physiological role of short-lived endogenous GLP-1 remains unclear largely because of its limited access to pancreatic β-cells. Here, we used d-allulose, a nonmetabolizable noncaloric rare sugar, as a GLP-1 secretagogue. We show that d-allulose–induced intestinal GLP-1 […]

NKX2.2 is a transcription factor that regulates pancreatic islet β-cell identity and function; however, cofactor proteins that modulate the functional activity of NKX2.2 in β-cells are relatively unexplored. An unbiased proteomics screen identified chromodomain helicase DNA-binding protein 4 (CHD4) as an NKX2.2 interacting partner. CHD4 is a nucleosome remodeler that directs the appropriate differentiation, maturation […]

Glucose-dependent insulinotropic polypeptide (GIP[1–42]) increases glucagon levels in the presence of normal-to-low plasma glucose concentrations in individuals with type 1 diabetes (T1D), suggesting its potential use as a safeguard against hypoglycemia. We investigated the dose-dependent effects of exogenous full-length GIP[1–42] and its truncated variant GIP[1–30]NH2 on glucagon concentrations during insulin-induced hypoglycemia in individuals with T1D. […]

Female protection against cardiometabolic disease wanes after menopause, concomitant with a transition toward the male-like pattern of visceral adiposity. Since recruitment of adipose progenitor cells (APCs) to support adipose expansion is depot-specific and thought to maintain metabolic homeostasis, sex differences in the capacity for APC differentiation were explored as a mechanism underlying female cardiometabolic protection. […]

Diabetic retinopathy (DR), a major complication of diabetes that causes blindness, is characterized by hyperglycemia-induced vascular dysfunction of incompletely defined mechanisms. Our study demonstrated glycolytic pathway activation in a DR rat model, which led to lactate accumulation and elevated pan lysine lactylation. Reduced lactate levels ameliorate vascular dysfunction. Global lactylome analysis of rat retinal tissues […]