non-obese diabetic

ML351 是一种高度特异的15-LOX-1抑制剂，其 IC50=200 nM。它对 T1D 非肥胖糖尿病小鼠模型的血糖异常和β细胞氧化应激有抑制作用。它对相关同工酶 (5-LOX、血小板 12-LOX、15-LOX-2、绵羊 COX-1 和人 COX-2) 表现出良好的选择性(>250倍)。

FKGK 18 is an inhibitor of group VIA (GVIA) calcium-independent phospholipase A2 (iPLA2). It inhibits GVIA iPLA2 by 99.9% at 0.091 mole fraction in a mixed micelle activity assay and is selective for GVIA iPLA2 over GIVA cPLA2 and GV sPLA2 where it shows 80.8 and 36.8% inhibition, respectively. FKGK 18 inhibits iPLA2β activity in cytosolic extracts from INS-1 cells overexpressing iPLA2β (IC50 = ~50 nM) as well as iPLA2γ activity in mouse heart membrane fractions (IC50s = ~1-3 μM). It inhibits glucose-induced increases in prostaglandin E2 production and insulin secretion in human pancreatic islets when used at a concentration of 10 μM and inhibits thapsigargin-induced apoptosis in INS-1 cells overexpressing iPLA2β in a concentration-dependent manner. FKGK 18 (20 mg/kg, 3 times per week) reduces blood glucose levels in an intraperitoneal glucose tolerance test, decreases the incidence of diabetes, and increases serum insulin levels in non-obese diabetic (NOD) mice.

MBX-8025 is an agonist of peroxisome proliferator-activated receptor δ (PPARδ).1 It is greater than 750- and 2,500-fold selective for PPARδ over PPARα and PPARγ. MBX-8025 (10 mg/kg per day for eight weeks) reduces increases in fasting blood glucose and serum insulin levels, and decreases insulin resistance in Alms1 mutant (foz/foz) mice fed an atherogenic diet as a model of diet-induced obesity, type 2 diabetes, and non-alcoholic steatohepatitis (NASH).2 It also decreases serum alanine transaminase (ALT), as well as serum and hepatic cholesterol and triglyceride, levels and reduces markers of NASH in the same model. |1. Bays, H.E., Schwartz, S., Littlejohn, T., 3rd, et al. MBX-8025, a novel peroxisome proliferator receptor-δ agonist: Lipid and other metabolic effects in dyslipidemic overweight patients treated with and without atorvastatin. J. Clin. Endocrinol. Metab. 96(9), 2889-2897 (2011).|2. Haczeyni, F., Wang, H., Barn, V., et al. The selective peroxisome proliferator-activated receptor-delta agonist seladelpar reverses nonalcoholic steatohepatitis pathology by abrogating lipotoxicity in diabetic obese mice. Hepatol. Commun. 1(7), 663-674 (2017).

IGRP(206-214) 是一种肽，具有生物活性。它对应于非肥胖糖尿病型(NOD)小鼠中胰岛特异性葡萄糖6磷酸酶催化亚基相关蛋白（IGRP）的206-214残基，并能诱导此类小鼠产生糖尿病。此外，该肽对胰岛素原特异性T细胞有着特定的作用。

GAD65 (524-543) 是具有生物活性的肽，属于谷氨酸脱羧酶 65 (GAD65) 氨基酸片段 524-543。作为胰岛抗原的关键片段之一，该肽在自发性自身免疫性糖尿病非肥胖糖尿病 (NOD) 小鼠模型中，可诱导增殖性 T 细胞反应。GAD65 (524-543) 对T细胞克隆BDC2.5具有特异性刺激作用，但可能存在亲和力较低的问题。此外，p524-543免疫可增强NOD小鼠对通过BDC2.5 T细胞过继转移诱导的1型糖尿病的敏感性。

BDC2.5 mimotope 1040-51 is an effectively agonistic mimotope peptide for the diabetogenic T cell clone BDC2.5, isolated from non-obese diabetic (NOD) mice.