2006
DOI: 10.2337/db05-1602
|View full text |Cite
|
Sign up to set email alerts
|

Chronic Inhibition of Dipeptidyl Peptidase-4 With a Sitagliptin Analog Preserves Pancreatic β-Cell Mass and Function in a Rodent Model of Type 2 Diabetes

Abstract: Inhibitors of dipeptidyl peptidase-4 (DPP-4), a key regulator of the actions of incretin hormones, exert antihyperglycemic effects in type 2 diabetic patients. A major unanswered question concerns the potential ability of DPP-4 inhibition to have beneficial disease-modifying effects, specifically to attenuate loss of pancreatic ␤-cell mass and function. Here, we investigated the effects of a potent and selective DPP-4 inhibitor, an analog of sitagliptin (des-fluoro-sitagliptin), on glycemic control and pancrea… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

30
297
4
16

Year Published

2008
2008
2021
2021

Publication Types

Select...
5
3

Relationship

0
8

Authors

Journals

citations
Cited by 440 publications
(347 citation statements)
references
References 49 publications
30
297
4
16
Order By: Relevance
“…It is currently unclear whether long-term use of such agents will prevent or slow down the continuous decline in ␤-cell function and mass associated with progression of type 2 diabetes. Animal experiments show an increase in ␤-cell mass within weeks of treatment with dipeptidyl peptidase IV inhibitors and enhanced ␤-cell preservation (38).…”
Section: Diabetes and Pancreatic Exocrine Dysfunction Due To Mutationmentioning
confidence: 99%
“…It is currently unclear whether long-term use of such agents will prevent or slow down the continuous decline in ␤-cell function and mass associated with progression of type 2 diabetes. Animal experiments show an increase in ␤-cell mass within weeks of treatment with dipeptidyl peptidase IV inhibitors and enhanced ␤-cell preservation (38).…”
Section: Diabetes and Pancreatic Exocrine Dysfunction Due To Mutationmentioning
confidence: 99%
“…Previous studies have shown that low-dose STZ injection leads to the partial destruction of pancreatic beta cells and a high-fat diet (HFD) induces insulin resistance in rodents [21][22][23]. The degree of beta cell destruction and insulin resistance can be adjusted by dosage, duration and condition of STZ injection and HFD feeding [11,24].…”
Section: Introductionmentioning
confidence: 99%
“…The degree of beta cell destruction and insulin resistance can be adjusted by dosage, duration and condition of STZ injection and HFD feeding [11,24]. The effects of various glucose-lowering drugs (sulfonylurea, metformin, thiazolidinedione etc) have been examined in mice treated with low-dose STZ and HFD as a model of type 2 diabetes [22,23]. In the present study, we too generated a mouse model mimicking human type 2 diabetes using low-dose STZ and HFD to examine the effect of leptin infusion.…”
Section: Introductionmentioning
confidence: 99%
“…We also studied possible changes in alpha cells that could be affected by DPP4 inhibitors [7] and could influence glucose profile of diabetic mice. Contrary to the widespread conception that beta cells are selectively destroyed in type 1 diabetes, alpha cell mass was significantly reduced in untreated diabetic NOD mice compared with prediabetic NOD mice (ESM Fig.…”
Section: Resultsmentioning
confidence: 99%
“…However, the supply of islets for transplantation is limited, precluding widespread application of islet transplantation for the treatment of type 1 diabetes. Strategies with potential beneficial effects on beta cell mass include glucagon-like peptide 1 (GLP-1) agonists [5,6] or inhibitors of dipeptidyl peptidase 4 (DPP4) [7,8], which degrades GLP-1 [9]. We have reported that a DPP4 inhibitor ameliorated diabetes induced by streptozotocin (STZ), and that this was attributable an increased beta cell mass [10].…”
mentioning
confidence: 99%