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.

GAD65 (524-543) acetate is a bioactive peptide, representing the amino acid sequence spanning the 524th to 543rd residues of glutamic acid decarboxylase 65 (GAD65). This compound is one of the initial segments found to induce proliferative T cell responses in the non-obese diabetic (NOD) mouse model of spontaneous autoimmune diabetes. It serves as a specific stimulator, potentially exhibiting low affinity for the spontaneously arising diabetogenic T cell clone BDC2.5. Immunization with GAD65 (524-543) acetate can increase the susceptibility of NOD mice to type 1 diabetes induced by the adoptive transfer of BDC2.5 T cells.