title: The DPP4 inhibitor linagliptin delays the onset of diabetes and preserves β-cell mass in non-obese diabetic mice.
abstract: Recent data indicate that dipeptidyl peptidase 4 (DPP4) inhibitors have anti-inflammatory and β-cell-sparing effects in animal models of type 1 diabetes. To evaluate the effects of the DPP4 inhibitor linagliptin on β-cell mass and insulinitis, we examined the progression of diabetes (blood glucose >11  mmol/l) in non-obese diabetic (NOD) mice with terminal stereological assessment of cellular pancreatic changes. Female NOD mice were fed a normal chow diet or a diet containing linagliptin 0.083  g/kg chow for 60 days. At study end, the incidence of diabetes in linagliptin-treated mice was reduced by almost 50% compared with vehicle (10 of 31 mice vs 18 of 30 mice, P=0.021). The total islet mass and total β-cell mass, identified by insulin immunoreactivity, were greater in non-diabetic linagliptin-treated mice compared with non-diabetic vehicle-treated mice (P<0.01 for both) but were greatly reduced in diabetic mice irrespective of treatment. No changes were seen in the α, δ and γ endocrine cell pool. Moreover, the total mass of lymphocyte insulinitis was significantly reduced in linagliptin-treated mice compared with vehicle. The data indicate that linagliptin treatment delays the onset of diabetes in NOD mice by protecting β-cell mass.
authors: Gubra ApS, Agern Alle 1, 2970 Hørsholm, Denmark.
authors: Jacob
authors: J
authors: Jelsing
authors: Niels
authors: N
authors: Vrang
authors: Søren B
authors: SB
authors: van Witteloostuijn
authors: Michael
authors: M
authors: Mark
authors: Thomas
authors: T
authors: Klein
mesh_terms: D017668:Age of Onset; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D000069476:Linagliptin; D051379:Mice; D016688:Mice, Inbred NOD; D011687:Purines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007328:Insulin; D011687:Purines; D011799:Quinazolines; D000069476:Linagliptin; D018819:Dipeptidyl Peptidase 4; C545245:Dpp4 protein, mouse