P32/98

P32/98 hemifumarateis a potent inhibitor of dipeptidyl peptidase IV with a Ki value of 130 nM. P32/98 hemifumarate improves glucose tolerance, insulin sensitivity and β-cell responsiveness in fatty Zucker rat model[1][2][3].

Signaling Pathways >> Metabolic Enzyme/Protease >> Dipeptidyl Peptidase

Research Areas >> Metabolic Disease

DPP-IV:130 nM (Ki)

GLP-1 acts function of stimulation of glucose dependent insulin secretion and induction of satiety feelings, and DPPIV is the major renal catabolic pathway for GLP-1 in vivo[2]. P32/98 hemifumarate, together with 200 pM GLP-1, (10 μM; 3 h) shows no significant inhibition of sodium re-absorption in porcine proximal tubular cells[2]. P32/98 hemifumarate (10 μM; 96 h) does not influence the mRNA expression of GLP-1R, DPPIV, Na+/H+ exchanger isoform 3 (NHE3), sodium-dependent glucose transporter slc5a1, slc5a2 (SGLT1, 2)[2]. Cell Cytotoxicity Assay[2] Cell Line: Porcine proximal tubular cells Concentration: 10 μM Incubation Time: 96 hours Result: Showed no toxic.

P32/98 hemifumarate (25 mg/kg; i.g.; once daily) long-time treatment significantly improves the glucose tolerance in Zucker diabetic fatty rats, a model of IGT (impaired glucose tolerance)[3]. Animal Model: Zucker diabetic fatty rat[3] Dosage: 25 mg/kg Administration: Oral gavage; once daily Result: Significantly improved the glucose tolerance in Zucker diabetic fatty rats.

[1]. Augstein P, et al. Efficacy of the dipeptidyl peptidase IV inhibitor isoleucine thiazolidide (P32/98) in fatty Zucker rats with incipient and manifest impaired glucose tolerance. Diabetes Obes Metab. 2008;10(10):850-861.

[2]. Schlatter P, et al. Glucagon-like peptide 1 receptor expression in primary porcine proximal tubular cells. Regul Pept. 2007 Jun 7;141(1-3):120-8. 

[3]. Wargent E, et al. Improvement of glucose tolerance in Zucker diabetic fatty rats by long-term treatment with the dipeptidyl peptidase inhibitor P32/98: comparison with and combination with rosiglitazone. Diabetes Obes Metab. 2005;7(2):170-181.