High Fat Diet and High Fructose Diet-fed Male and Female Liv-ARKO Mice Displayed Impair Glucose-Stimulated Insulin Secretion.

Insulin resistance affects up to a third of the US adult population and polycystic ovary syndrome (PCOS) affects up to 10% of reproductive-age adult women. The liver plays an essential component in the metabolism of insulin and androgen signaling. Hyperandrogenism in females can also increase predisposition to insulin resistance. In our study, we placed female and male liver androgen receptor knock-out mice (Liv-ARKO) on high fructose diets (HFrD) and high fat diets (HFD) to determine if Liv-ARKO mice demonstrated altered glucose-stimulated insulin secretion on special diets compared to a control diet. In this study, female and male Liv-ARKO mice were placed on three distinct diets: Control (Research Diets Inc), High Fat (HFD), and High Fructose (HFrD). After one month and two months on these diets, Glucose-Stimulated Insulin Secretion tests were performed: each group was injected with a 20% glucose solution at 2g of glucose/kg body mass and blood samples were taken via tail milking at 0 minutes, 15 minutes, and 30 minutes. Blood samples were immediately centrifuged and serum supernatant was extracted for further analysis via Sigma Insulin Assay. In the current study, after two months, female mice on HFrD demonstrated lower basal insulin levels compared to female mice fed a control diet. Interestingly, mice on a HFD showed insulin levels that were lower than the basal levels of both control mice and HFrD mice. Furthermore, compared to the control mice, the HFD mice demonstrated lower insulin levels at both basal level and 30 minutes post-glucose administration. It was hypothesized that HFD and HFrD-fed Liv-ARKO mice would impair glucose-stimulated insulin secretion, which our current study supports. These data suggest that diets high in fructose and fat both blunt insulin secretion following a meal, and to a greater extent in high fat diets. This dysfunction may ultimately play a role in the development of insulin resistance. More research is necessary in order to further investigate the effects of high fat and high fructose diets on glucose-stimulated insulin secretion and consequent development of insulin resistance.