Inhibition of DPP-4 with sitagliptin improves glycemic control and restores islet cell mass and function in a rodent model of type 2 diabetes

Both sitagliptin analogue & pioglitazone preserve the β-cell proportion in the islets with different mechanism in non-obese and obese diabetic mice

“…This may be a consequence of unresolved hyperglycemic excursion or a characteristic difference specifically inherent to the db/db mouse itself. In this study, islet mass did not increase after administration of either SITA or PIO in either model, which is inconsistent with the results of other studies (7,18,31).We suggest that the 4-6-week treatment period used in this study was not sufficiently long for the β-cell mass to be altered significantly in either animal model. Moreover, the β-cell mass at any specific time should not be viewed as an accurate reflection of the actual β-cell reservoir, since islet cells retain their plasticity via a dynamic mechanism involving regeneration, proliferation, and apoptosis (32)(33)(34).…”

“…Thus, in this study, we employed db/ db and Akita mice as models of obese and non-obese patients with T2DM, respectively. Recently, incretin-based therapy has attracted increasing attention in regard to its possible use for the treatment of type 2 http://bmbreports.org diabetes, via the potentiation of glucose-dependent insulin secretion (16) and prevention of β-cell mass loss in diabetic animal models (17,18), which has never previously been achieved by any treatments. Theoretically, SITA, which is a DPP-4 inhibitor, should be more potent in Akita mice due to an improvement in the principal defect, i.e., impaired insulin secretion, but not in db/db mice, which exhibit basal hyperinsulinemia that results from insulin resistance.…”

Impaired expression of sex hormone receptors in male reproductive organs of diabetic rat in response to oral antidiabetic drugs

“…This study aimed to evaluate the effects of the commonly used oral antidiabetics; metformin, pioglitazone and sitagliptin on the structure of male reproductive system in a STZ-induced diabetic rats. It was observed that the therapies studied in this work succeeded in controlling the STZ-induced diabetic [24], pioglitazone [23] and sitagliptin [36,37]. Although the weights of testis, epididymis and seminal vesicle as well as testosterone hormone level was significantly reduced in the STZ-induced diabetic rats and these findings were consistent with those of previous studies [38][39][40][41], metformin succeeded to restore it back to values with insignificant difference compared to the NC group while the pioglitazone and sitagliptin failed to do that.…”

Use of DPP-4 inhibitors in type 2 diabetes: focus on sitagliptin

“…The long-term durability is now important to consider and of high importance for the future long-term value of this class of compounds. Whether sitagliptin may have additional beneficial effects on islet mass, as has been shown in rodents, 26 remains to be established in humans. In the clinical context, sitagliptin offers similar indication as the other DPP-4 inhibitors and the GLP-1 receptor agonists.…”

“…24,25 Rodent studies have also shown that DPP-4 inhibitors (vildagliptin and sitagliptin) increase islet mass and normalize islet cell topography in diabetes models in mice. 26,27 This would suggest that DPP-4 inhibition targets the important islet dysfunctions in type 2 diabetes. It should be emphasized, however, that no evidence of increased β-cell mass by DPP-4 inhibitors exists in humans.…”