non-obese diabetic

ML351 is a potent and selective inhibitor of human 15-lipoxygenase-1 (15 LOX)(IC50: 200 nM).

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) is an bioactive peptide corresponding to residues 206–214 of the murine islet-specific glucose-6-phosphatase catalytic subunit–related protein (IGRP). It induces diabetes in non-obese diabetic (NOD) mice by being specific for T cells targeting both proinsulin and IGRP.

GAD65 (524-543) is a biologically active peptide comprising amino acids 524 to 543 of glutamic acid decarboxylase 65 (GAD65). It represents an early islet antigen fragment that elicits proliferative T cell responses in the non-obese diabetic (NOD) mouse model, instrumental in spontaneous autoimmune diabetes research. The peptide serves as a specific, possibly low-affinity stimulant for the diabetogenic T cell clone BDC2.5. Notably, immunization with GAD65 (524-543) heightens NOD mice's vulnerability to type 1 diabetes when subjected to the adoptive transfer of BDC2.5 T cells.

BDC2.5 mimotope 1040-51 is a mimotope peptide for the diabetogenic T cell clone BDC2.5, isolated from non-obese diabetic (NOD) mice. This effectively agonistic peptide prompts T cells from prediabetic and diabetic NOD mice to respond to BDC2.5 mimotope peptides.