Category: Diabetes

GRP78/BiP/HSPA5 is a widely expressed endoplasmic reticulum (ER) chaperone that also performs the critical role of regulating the unfolded protein response, an adaptive mechanism that maintains ER homeostasis. As the exclusive source of circulating insulin, pancreatic β-cells are prone to ER stress due to proinsulin synthesis workload. GRP78 is important for the ER stress response, […]

Progressive loss of pancreatic β-cell mass (BCM) is a hallmark of type 2 diabetes, yet strategies to preserve or restore BCM remain elusive due to incomplete understanding of the molecular mechanisms governing β-cell proliferation in adults. The unfolded protein response (UPR) maintains endoplasmic reticulum (ER) proteostasis, but the in vivo role of activating transcription factor 6α […]

Glucokinase and ATP-sensitive potassium (KATP) channels in pancreatic β-cells control insulin secretion in response to glucose stimulation to maintain glucose homeostasis. It is well established that loss-of-function (LOF) variants in GCK, which encodes glucokinase, are diabetogenic, whereas LOF variants in KATP channel genes lead to congenital hyperinsulinism (HI) and hypoglycemia. However, how the co-occurrence of […]

This study characterized the dose effect of whey protein isolate (WPI) ingestion on glucagon secretion, glycemia, and the underlying mechanisms in adults with type 1 diabetes. Twelve insulin pump–treated adults with type 1 diabetes (mean ± SD age 47.3 ± 16.4 years; BMI 26.1 ± 3.8 kg/m2) and six adults without diabetes (age 36.2 ± […]

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 […]