DPP-4 inhibition improves early mortality, β cell function, and adipose tissue inflammation in db/db mice fed a diet containing sucrose and linoleic acid.
BACKGROUND
Diabetes therapy that not only lowers glucose levels but also lengthens life spans is required. We previously demonstrated that DPP-4 inhibition ameliorated β cell apoptosis and adipose tissue inflammation in β cell-specific glucokinase haploinsufficient mice fed a diet containing a combination of sucrose and linoleic acid (SL).


METHODS
In this study, we investigated the effects of DPP-4 inhibition in obese diabetic db/db mice fed an SL diet or a control diet containing sucrose and oleic acid (SO). We also examined the effects of DPP-4 inhibition in IRS-1-deficient mice fed an SL or SO diet as a model of insulin resistance.


RESULTS
DPP-4 inhibition efficiently increases the active GLP-1 levels in db/db mice. Unexpectedly, the SL diet, but not the SO diet, markedly increases mortality in the db/db mice. DPP-4 inhibition reduces the early lethality in SL-fed db/db mice. DPP-4 inhibition improves glucose tolerance, β cell function, and adipose tissue inflammation in db/db mice fed either diet. No significant changes in glycemic control or β cell mass were observed in any of the IRS-1-deficient mouse groups.


CONCLUSIONS
A diet containing a combination of sucrose and linoleic acid causes early lethality in obese diabetic db/db mice, but not in lean and insulin resistant IRS-1 knockout mice. DPP-4 inhibition has protective effects against the diet-induced lethality in db/db mice.
['Shirakawa|Jun|J|', 'Okuyama|Tomoko|T|', 'Kyohara|Mayu|M|', 'Yoshida|Eiko|E|', 'Togashi|Yu|Y|', 'Tajima|Kazuki|K|', 'Yamazaki|Shunsuke|S|', 'Kaji|Mitsuyo|M|', 'Koganei|Megumi|M|', 'Sasaki|Hajime|H|', 'Terauchi|Yasuo|Y|']
Adipose tissue Life span Insulin resistance DPP-4 inhibitor Pancreatic β cell Type 2 diabetes