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, […]
Read MoreCategory: Diabetes
Gut-Derived GLP-1 Released by Rare Sugar d -Allulose Cooperates With Insulin to Activate Left-Sided Vagal Afferents and Enhance Insulin Sensitivity
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 […]
Read MoreCHD4 and NKX2.2 Cooperate to Regulate β-Cell Function by Repressing Non–β-Cell Gene Programs
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 […]
Read MoreThe Glucagonotropic Effect of GIP Is Negated During Insulin-Induced Hypoglycemia in Type 1 Diabetes: A Randomized, Placebo-Controlled, Crossover Study
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. […]
Read MoreEstrogen Mediates Capacity for Hyperplastic Adipose Expansion and Preserves Adipose Progenitor Cell Availability in Subcutaneous Depots of Female Mice
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. […]
Read MoreHMGA1 Lactylation–Mediated Regulation of the SP1/VEGFA Axis in Pathological Angiogenesis Under Diabetic Retinopathy
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 […]
Read MoreDistinct Interplay Between β-Cell Function and Insulin Resistance in Latent Autoimmune Diabetes in Adults Versus Type 2 Diabetes
We conducted a cross-sectional study to explore the interplay between β-cell function and peripheral insulin resistance in latent autoimmune diabetes in adults (LADA) compared with type 2 diabetes. Thirty-one people with LADA were matched for sex, BMI, and disease duration with 31 people with type 2 diabetes. Insulin resistance was estimated using established surrogate indexes, […]
Read MoreGlycemic Improvement and Active Charcot Neuroarthropathy: Osteocalcin as a Candidate Biomarker of Transient Skeletal Vulnerability
Active Charcot neuroarthropathy (CN) remains difficult to predict. This hypothesis-generating article proposes a deliberately restricted, testable model in which a clinically meaningful fall in HbA1c may temporally coincide with active CN in a subset of people with diabetes, established neuropathy, and a vulnerable foot. The signal is based on a sequence of observations—an initial case […]
Read MoreProtection Against Periodontitis by Improving Mitochondrial Function in Diabetes
Diabetes is a major risk factor for severe periodontitis. This is partly due to impaired wound healing associated with concomitant failure to resolve inflammation and chronic infection. Studies from the Joslin Medalist Cohort, people with >50 years of type 1 diabetes, have reported that protective factors exist to delay the onset of severe retinopathy, nephropathy, […]
Read MoreActivation of Intestinal Type 3 Innate Lymphoid Cells and Regulatory T Cells Through Free Fatty Acid Receptor 2 Ameliorates Type 1 Diabetes in Mice
Reduction in intestinal type 3 innate lymphoid cells (ILC3) frequency is associated with type 1 diabetes (T1D) pathogenesis in humans and in animal models. The current study showed that, after T1D induction by multiple–low-dose streptozotocin in male C57BL/6 mice, ILC3 were reduced in both blood and pancreas and produced less IL-22 and IL-2, and a […]
Read More