General Information:

Id: 2,046
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mus musculus
genetically diabetic C57BL/KSJ db/db mouse
BTO:0000991 pancreatic islet
article
Reference: Cheng Q et al.(2008) Combination of the dipeptidyl peptidase IV inhibitor LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] with the angiotensin II type 1 receptor antagonist valsartan [N-(1-oxopentyl)-N-[[2-(1H-tetrazol-5-yl)-[1,1-biphenyl]-4-yl]methyl]-L-valine] enhances pancreatic islet morphology and function in a mouse model of type 2 diabetes. J. Pharmacol. Exp. Ther. 327: 683-691 [PMID: 18787107]

Interaction Information:

Comment LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] is an inhibitor of dipeptidyl peptidase IV that delays the degradation of glucagon-like peptide-1 (GLP-1).
Formal Description
Interaction-ID: 16336

drug/chemical compound

LAF237

decreases_activity of

gene/protein

DPP4

Drugbank entries Show/Hide entries for DPP4
Comment Valsartan [N-(1-oxopentyl)-N-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-l-valine] is an antagonist of the angiotensin II type 1 receptor (AT1R) that reduces the incidence of type 2 diabetes mellitus.
Formal Description
Interaction-ID: 16338

drug/chemical compound

Valsartan

decreases_activity of

gene/protein

AGTR1

Drugbank entries Show/Hide entries for Valsartan or AGTR1
Comment Valsartan [N-(1-oxopentyl)-N-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-l-valine] is an antagonist of the angiotensin II type 1 receptor (AT1R) that reduces the incidence of type 2 diabetes mellitus.
Formal Description
Interaction-ID: 16339

drug/chemical compound

Valsartan

decreases_activity of

Drugbank entries Show/Hide entries for Valsartan
Comment To measure the acute effect of the treatment, pancreatic islets of db/db mice were isolated and stimulated in vitro with glucose in the presence of valsartan (1 microM) and exendin-4 (100 nM), a GLP-1 receptor agonist.
Formal Description
Interaction-ID: 16340

drug/chemical compound

Exendin-4

increases_activity of

gene/protein

GLP1R

Drugbank entries Show/Hide entries for GLP1R
Comment Glucose-stimulated insulin release was significantly reduced in islets from obese db/db mice, compared with the control mice. Exendin-4 and valsartan significantly doubled glucose-induced insulin release of db/db isolated islets. A clear synergetic effect was observed with the combination to the extent that these levels were comparable with those in normal m/db islets.
Formal Description
Interaction-ID: 16370

drug/chemical compound

Valsartan

increases_activity of

in pancreas, in pancreatic islets; in db/db mice
Drugbank entries Show/Hide entries for Valsartan
Comment Glucose-stimulated insulin release was significantly reduced in islets from obese db/db mice, compared with the control mice. Exendin-4 and valsartan significantly doubled glucose-induced insulin release of db/db isolated islets. A clear synergetic effect was observed with the combination to the extent that these levels were comparable with those in normal m/db islets.
Formal Description
Interaction-ID: 16371

drug/chemical compound

Exendin-4

increases_activity of

in pancreas, in pancreatic islets; in db/db mice
Comment After treatment with LAF237 and/or valsartan for 8 weeks, pancreatic beta-cell area was increased in all treatment groups. The improvement was similar in both LAF237- and valsartan-treated groups but was statistically greater with the combination therapy.
Formal Description
Interaction-ID: 16372

drug/chemical compound

LAF237

increases_quantity of

tissue/cell line

pancreatic beta cell

in pancreas, in pancreatic islets
Comment After treatment with LAF237 and/or valsartan for 8 weeks, pancreatic beta-cell area was increased in all treatment groups. The improvement was similar in both LAF237- and valsartan-treated groups but was statistically greater with the combination therapy.
Formal Description
Interaction-ID: 16374

drug/chemical compound

Valsartan

increases_quantity of

tissue/cell line

pancreatic beta cell

in pancreas, in pancreatic islets
Drugbank entries Show/Hide entries for Valsartan
Comment Beta-cell proliferation in the valsartan-treated group and in the LAF237-treated group was significantly higher than in the db/db diabetic mice group treated with H2O. Compared with either treatment alone, the beta-cell proliferation was highly and significantly stimulated by the combined treatment.
Formal Description
Interaction-ID: 16376

drug/chemical compound

Valsartan

increases_activity of

in pancreas, in pancreatic islets; in db/db mice
Drugbank entries Show/Hide entries for Valsartan
Comment Beta-cell proliferation in the valsartan-treated group and in the LAF237-treated group was significantly higher than in the db/db diabetic mice group treated with H2O. Compared with either treatment alone, the beta-cell proliferation was highly and significantly stimulated by the combined treatment.
Formal Description
Interaction-ID: 16378

drug/chemical compound

LAF237

increases_activity of

in pancreas, in pancreatic islets; in db/db mice
Comment A decrease in ROS-induced islet apoptosis was observed in both valsartan- and LAF237-treated groups, the combined treatment reduced islet apoptosis further.
Formal Description
Interaction-ID: 16379

drug/chemical compound

Valsartan

decreases_activity of

in pancreas, in pancreatic islets
Drugbank entries Show/Hide entries for Valsartan
Comment A decrease in ROS-induced islet apoptosis was observed in both valsartan- and LAF237-treated groups, the combined treatment reduced islet apoptosis further.
Formal Description
Interaction-ID: 16380

drug/chemical compound

LAF237

decreases_activity of

in pancreas, in pancreatic islets
Comment Fibronectin and collagen I mRNA expression was similarly decreased in db/db mice treated with LAF237 or valsartan monotherapy. However, the reduction of those genes was significantly stronger in db/db mice groups with the combined treatment.
Formal Description
Interaction-ID: 16381

drug/chemical compound

Valsartan

decreases_expression of

gene/protein

FN1

in pancreas, in pancreatic islets; in db/db mice
Drugbank entries Show/Hide entries for Valsartan
Comment Fibronectin and collagen I mRNA expression was similarly decreased in db/db mice treated with LAF237 or valsartan monotherapy. However, the reduction of those genes was significantly stronger in db/db mice groups with the combined treatment.
Formal Description
Interaction-ID: 16382

drug/chemical compound

Valsartan

decreases_expression of

gene/protein

COL1A1

in pancreas, in pancreatic islets; in db/db mice
Drugbank entries Show/Hide entries for Valsartan or COL1A1
Comment Fibronectin and collagen I mRNA expression was similarly decreased in db/db mice treated with LAF237 or valsartan monotherapy. However, the reduction of those genes was significantly stronger in db/db mice groups with the combined treatment.
Formal Description
Interaction-ID: 16383

drug/chemical compound

LAF237

decreases_expression of

gene/protein

FN1

in pancreas, in pancreatic islets; in db/db mice
Comment Fibronectin and collagen I mRNA expression was similarly decreased in db/db mice treated with LAF237 or valsartan monotherapy. However, the reduction of those genes was significantly stronger in db/db mice groups with the combined treatment.
Formal Description
Interaction-ID: 16384

drug/chemical compound

LAF237

decreases_expression of

gene/protein

COL1A1

in pancreas, in pancreatic islets; in db/db mice
Drugbank entries Show/Hide entries for COL1A1
Comment Fibronectin and collagen I mRNA expression was similarly decreased in db/db mice treated with LAF237 or valsartan monotherapy. However, the reduction of those genes was significantly stronger in db/db mice groups with the combined treatment.
Formal Description
Interaction-ID: 16385

drug/chemical compound

Valsartan

decreases_activity of

phenotype

fibrosis

in pancreas, in pancreatic islets; in db/db mice
Drugbank entries Show/Hide entries for Valsartan
Comment Fibronectin and collagen I mRNA expression was similarly decreased in db/db mice treated with LAF237 or valsartan monotherapy. However, the reduction of those genes was significantly stronger in db/db mice groups with the combined treatment.
Formal Description
Interaction-ID: 16386

drug/chemical compound

LAF237

decreases_activity of

phenotype

fibrosis

in pancreas, in pancreatic islets; in db/db mice
Comment In the db/db mice with H2O treatment, strong labeling of fibronectin and collagen I was observed relative to m+/db mice.
Formal Description
Interaction-ID: 16387

organism model

db/db mouse

increases_expression of

gene/protein

FN1

in pancreas, in pancreatic islets
Comment In the db/db mice with H2O treatment, strong labeling of fibronectin and collagen I was observed relative to m+/db mice.
Formal Description
Interaction-ID: 16388

organism model

db/db mouse

increases_expression of

gene/protein

COL1A1

in pancreas, in pancreatic islets
Drugbank entries Show/Hide entries for COL1A1
Comment In the db/db mice with H2O treatment, strong labeling of fibronectin and collagen I was observed relative to m+/db mice.
Formal Description
Interaction-ID: 16389

organism model

db/db mouse

increases_activity of

phenotype

fibrosis

in pancreas, in pancreatic islets
Comment A significant decrease in superoxide formation in pancreatic islets was found with both LAF237 and valsartan alone, the beneficial effect against oxidative stress was twice as great with combination therapy.
Formal Description
Interaction-ID: 16390

drug/chemical compound

LAF237

decreases_quantity of

drug/chemical compound

O2-

in pancreas, in pancreatic islets
Comment A significant decrease in superoxide formation in pancreatic islets was found with both LAF237 and valsartan alone, the beneficial effect against oxidative stress was twice as great with combination therapy.
Formal Description
Interaction-ID: 16391

drug/chemical compound

Valsartan

decreases_quantity of

drug/chemical compound

O2-

in pancreas, in pancreatic islets
Drugbank entries Show/Hide entries for Valsartan
Comment A significant decrease in superoxide formation in pancreatic islets was found with both LAF237 and valsartan alone, the beneficial effect against oxidative stress was twice as great with combination therapy.
Formal Description
Interaction-ID: 16392

drug/chemical compound

LAF237

decreases_activity of

in pancreas, in pancreatic islets
Comment A significant decrease in superoxide formation in pancreatic islets was found with both LAF237 and valsartan alone, the beneficial effect against oxidative stress was twice as great with combination therapy.
Formal Description
Interaction-ID: 16393

drug/chemical compound

Valsartan

decreases_activity of

in pancreas, in pancreatic islets
Drugbank entries Show/Hide entries for Valsartan
Comment The expression and localization of nitrotyrosine were determined in pancreatic islets, the nitrotyrosine-positive-stained area was decreased after LAF237 or valsartan alone, the effect was stronger in the combined treatment group.
Formal Description
Interaction-ID: 16394

drug/chemical compound

Valsartan

decreases_quantity of

drug/chemical compound

3-Nitrotyrosine

in pancreas, in pancreatic islets
Drugbank entries Show/Hide entries for Valsartan
Comment The expression and localization of nitrotyrosine were determined in pancreatic islets, the nitrotyrosine-positive-stained area was decreased after LAF237 or valsartan alone, the effect was stronger in the combined treatment group.
Formal Description
Interaction-ID: 16395

drug/chemical compound

LAF237

decreases_quantity of

drug/chemical compound

3-Nitrotyrosine

in pancreas, in pancreatic islets
Comment Hyperglycemia and glucose intolerance in db/db diabetic mice were reduced by LAF237 or valsartan alone and after the combination therapy. Surprisingly, combination treatment was not superior to the monotherapy.
Formal Description
Interaction-ID: 16396

drug/chemical compound

LAF237

decreases_activity of

phenotype

hyperglycemia

in db/db mice
Comment Hyperglycemia and glucose intolerance in db/db diabetic mice were reduced by LAF237 or valsartan alone and after the combination therapy. Surprisingly, combination treatment was not superior to the monotherapy.
Formal Description
Interaction-ID: 16397

drug/chemical compound

Valsartan

decreases_activity of

phenotype

hyperglycemia

in db/db mice
Drugbank entries Show/Hide entries for Valsartan
Comment Hyperglycemia and glucose intolerance in db/db diabetic mice were reduced by LAF237 or valsartan alone and after the combination therapy. Surprisingly, combination treatment was not superior to the monotherapy.
Formal Description
Interaction-ID: 16398

drug/chemical compound

LAF237

decreases_activity of

in db/db mice
Comment Hyperglycemia and glucose intolerance in db/db diabetic mice were reduced by LAF237 or valsartan alone and after the combination therapy. Surprisingly, combination treatment was not superior to the monotherapy.
Formal Description
Interaction-ID: 16399

drug/chemical compound

Valsartan

decreases_activity of

in db/db mice
Drugbank entries Show/Hide entries for Valsartan