Cutting Edge: ST8Sia6-Generated α-2,8-Disialic Acids Mitigate Hyperglycemia in Multiple Low-Dose Streptozotocin-Induced Diabetes.
Paul J BelmonteMichael Jeremy ShapiroMatthew J RajculaShaylene A McCueVirginia Smith ShapiroPublished in: Journal of immunology (Baltimore, Md. : 1950) (2020)
The immune system contains a series of checks and balances that maintain tolerance and prevent autoimmunity. Sialic acid-binding Ig-type lectins (Siglecs) are cell surface receptors found on immune cells and inhibit inflammation by recruiting protein tyrosine phosphatases to ITIMs. Islet-resident macrophages express Siglec-E, and Siglec-E expression decreases on islet-resident macrophages as insulitis progresses in the NOD mouse. The sialyltransferase ST8Sia6 generates α-2,8-disialic acids that are ligands for Siglec-E in vivo. We hypothesized that engaging Siglec-E through ST8Sia6-generated ligands may inhibit the development of immune-mediated diabetes. Constitutive overexpression of ST8Sia6 in pancreatic β cells mitigated hyperglycemia in the multiple low-dose streptozotocin model of diabetes, demonstrating that engagement of this immune receptor facilitates tolerance in the setting of inflammation and autoimmune disease.
Keyphrases
- diabetic rats
- oxidative stress
- low dose
- type diabetes
- induced apoptosis
- cell surface
- cardiovascular disease
- glycemic control
- binding protein
- high fat diet
- high dose
- patient safety
- poor prognosis
- quality improvement
- multiple sclerosis
- cell cycle arrest
- metabolic syndrome
- endoplasmic reticulum stress
- protein protein
- cell death
- emergency medicine
- amino acid
- weight loss