Vascepa protects against high-fat diet-induced glucose intolerance, insulin resistance, and impaired β-cell function

Abstract

Summary Omega-3 fatty acid prescription drugs, Vascepa (≥96% eicosapentaenoic acid [EPA] ethyl ester) and Lovaza (46.5% EPA and 37.5% docosahexaenoic acid ethyl ester) are known therapeutic regimens to treat hypertriglyceridemia. However, their impact on glucose homeostasis, progression to type 2 diabetes, and pancreatic beta cell function are not well understood. In the present study, mice were treated with Vascepa or Lovaza for one week prior to six weeks of high-fat diet feeding. Vascepa but not Lovaza led to reduced insulin resistance, reduced fasting insulin and glucose, and improved glucose intolerance. Vascepa improved beta cell function, reduced liver triglycerides with enhanced expression of hepatic fatty acid oxidation genes, and altered microbiota composition. Vascepa has protective effects on diet-induced insulin resistance and glucose intolerance in mice.

Using Mendelian randomisation to identify opportunities for type 2 diabetes prevention by repurposing medications used for lipid management

“…It is possible that the reduced T2D risk associated with IPE is only observed in the context of a high-fat diet, such as was observed in mice. 9 Despite the null associations reported for IPE in primary T2D prevention, a substantial CVD risk reduction (RR= 0·77, 95% CI= 0·66, 0·88; P = 3·0 × 10 −4 ) was observed among REDUCE-IT participants with baseline T2D who were treated with IPE compared to placebo – indicating the potential interaction (perhaps synergistic effect) between statins and IPE on CVD prevention. 31 …”

“… 7 Moreover, EPA metabolites have been shown to prevent hyperglycemia and hyperinsulinemia in humans, 8 and in mice IPE is protective against high-fat diet-induced glucose intolerance, insulin resistance, and β-cell dysfunction. 9 We therefore hypothesized that IPE could perhaps be used for T2D prevention. While researchers have rightfully focused on identifying agents for CVD prevention, discovering new putative therapies for T2D prevention could help lower T2D burden and ensuing complications, including CVD.…”

A protocol for studying glucose homeostasis and islet function in mice

“…Student’s T-test was used for the AUC bar graphs. Permission has been obtained to re-use results from Al Rijjal et al. (2021).…”

“…This protocol enables evaluation of glucose homeostasis and islets in mice which can also be applied to rat, beta cell lines and human studies. For complete details on the use and execution of this profile, please refer to Al Rijjal et al. (2021) .…”

“…For complete details on the use and execution of this profile, please refer to Al Rijjal et al. (2021) .…”