Vildagliptin selectively ameliorates GLP-1, GLUT4, SREBP-1c mRNA levels and stimulates β-Cell proliferation resulting in improved glucose homeostasis in rats with streptozotocin-induced diabetes

Akarte, Atul Sureshrao; Srinivasan, B.P.; Gandhi, Sonia

doi:10.1016/j.jdiacomp.2012.03.013

Cited by 31 publications

(25 citation statements)

References 43 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with these reports, our results showed an increase in TNF-a and IL-6 levels in diabetic myocardial tissues as well as fat deposition in diabetic myocardial and epicardial tissues. However, sitagliptin could reduce the expression of TNF-a and IL-6 and fat deposition in the diabetic heart, so sitagliptin might lower the morbidity and mortality of diabetic complications associated with inflammation (22,23).…”

Section: Discussionmentioning

confidence: 99%

Sitagliptin alleviated myocardial remodeling of the left ventricle and improved cardiac diastolic dysfunction in diabetic rats

Liu

Huang

Wang

et al. 2015

Journal of Pharmacological Sciences

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Sitagliptin alleviated myocardial remodeling of the left ventricle and improved cardiac diastolic dysfunction in diabetic rats

Liu

Huang

Wang

et al. 2015

Journal of Pharmacological Sciences

View full text Add to dashboard Cite

show abstract

“…In fact, pancreatic beta-cell specific C/EBPbeta transgenic mice exhibit diabetes and decreased beta-cell mass associated with increased apoptosis, decreased proliferation, and aggravated ER stress, and these can be restored by oral administration of vildagliptin [34]. Treatment of rats with vildagliptin significantly increased insulin content and decreased inflammatory markers such as nitric oxide and TNF-α [35,36]. Chronic administration of vildagliptin in IRS-2 KO mice improved glucose metabolism and suppressed beta-cell apoptosis, suggesting that vildagliptin may also activate beta-cell proliferation independent of IRS-2 axis [37].…”

Section: Discussionmentioning

confidence: 99%

Effects of combination therapy with vildagliptin and valsartan in a mouse model of type 2 diabetes

Miyagawa

Kondo

Goto

et al. 2013

Cardiovasc Diabetol

View full text Add to dashboard Cite

BackgroundDipeptidyl peptidase-4 (DPP-4) inhibitors modulate incretin hormones and exert anti-diabetic effects in type 2 diabetes mellitus. Treatment with angiotensin II type 1 receptor blockers (ARB) is a proven successful intervention for hypertension with type 2 diabetes. The present study investigated the combined effects of the DPP-4 inhibitor vildagliptin and the ARB valsartan in a mouse model of type 2 diabetes.MethodsC57BL/6 J mice fed with high-fat diet (HFD) or db/db mice were treated with placebo, phloridzin (PHZ), vildagliptin alone (ViL), valsartan alone (VaL) or ViL with VaL (ViLVaL) for 8 weeks.ResultsGlucose metabolism was improved in response to PHZ, ViL and ViLVaL in both HFD and db/db mice. Upon glucose challenge, ViLVaL showed the greatest suppression of blood glucose excursions, with increased insulin secretion, in db/db mice. ViLVaL treatment also showed an improvement of insulin sensitivity in db/db mice. Serum inflammatory cytokines were significantly decreased, and adiponectin was highest, in the ViLVaL group. ViLVaL improved insulin signaling and attenuated stress signaling in liver with amelioration of hepatic steatosis due to activated fatty acid oxidation in db/db mice. Furthermore, immunohistochemical analysis of the pancreas revealed that the combination treatment resulted in an increased expression of insulin and PDX-1, and increased insulin content.ConclusionsThe combination therapy of ViL and VaL improves both pancreatic beta-cell function and insulin sensitivity, with a reduction of the inflammatory and cell stress milieu in mouse models of T2DM. Our results suggest that this combination therapy exerts additive or even synergistic benefits to treat T2DM.

show abstract

“…The iPLA 2 ␤ gene contains a sterol regulatory element (SRE) ( 126 ). Under stressful conditions SREBPs are processed to mature forms of SREBPs (127)(128)(129)(130)(131)(132)(133)(134)(135), which translocate to the nucleus and bind to SRE. This leads to induction of iPLA 2 ␤ transcription and protein expression, which are suppressed in the presence of a dominant negative form of SREBP-1 ( 136-138 ).…”

Section: Proposed Roles For Ipla 2 ␤mentioning

confidence: 99%

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

Ramanadham

Ali

Ashley

et al. 2015

Journal of Lipid Research

168

190

View full text Add to dashboard Cite

The Ca 2+ -independent phospholipases A 2 (iPLA 2 s) are part of a diverse family of PLA 2 s that hydrolyze the sn -2 substituent from membrane phospholipids to release a free fatty acid and a lysolipid ( 1, 2 ). These enzymes are ubiquitously expressed, and in contrast to secretory PLA 2 s (sPLA 2 s) and cytosolic PLA 2 s (cPLA 2 s), do not require Ca 2+ for either translocation or activity. Some of the fi rst descriptions of iPLA 2 activity were in the mid-to late-1980s with the identifi cation of a plasmalogen-selective PLA 2 in Abstract Among the family of phospholipases A 2 (PLA 2 s) are the Ca 2+ -independent PLA 2 s (iPLA 2 s) and they are designated group VI iPLA 2 s. In relation to secretory and cytosolic PLA 2 s, the iPLA 2 s are more recently described and details of their expression and roles in biological functions are rapidly emerging. The iPLA 2 s or patatin-like phospholipases (PNPLAs) are intracellular enzymes that do not require Ca 2+ for activity, and contain lipase (GXSXG) and nucleotide-binding (GXGXXG) consensus sequences. Though nine PNPLAs have been recognized, PNPLA8 (membraneassociated iPLA 2 ␥ ) and PNPLA9 (cytosol-associated iPLA 2 ␤ ) are the most widely studied and understood. The iPLA 2 s manifest a variety of activities in addition to phospholipase, are ubiquitously expressed, and participate in a multitude of biological processes, including fat catabolism, cell differentiation, maintenance of mitochondrial integrity, phospholipid remodeling, cell proliferation, signal transduction, and cell death. As might be expected, increased or decreased expression of iPLA 2 s can have profound effects on the metabolic state, CNS function, cardiovascular performance, and cell survival; therefore, dysregulation of iPLA 2 s can be a critical factor in the development of many diseases. This review is aimed at providing a general framework of the current understanding of the iPLA 2 s and discussion of the potential mechanisms of action of the iPLA 2 s and related involved lipid mediators. -Ramanadham, S

show abstract

Vildagliptin selectively ameliorates GLP-1, GLUT4, SREBP-1c mRNA levels and stimulates β-Cell proliferation resulting in improved glucose homeostasis in rats with streptozotocin-induced diabetes

Cited by 31 publications

References 43 publications

Sitagliptin alleviated myocardial remodeling of the left ventricle and improved cardiac diastolic dysfunction in diabetic rats

Sitagliptin alleviated myocardial remodeling of the left ventricle and improved cardiac diastolic dysfunction in diabetic rats

Effects of combination therapy with vildagliptin and valsartan in a mouse model of type 2 diabetes

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

Contact Info

Product

Resources

About