The Effect of Exercise on Hepatic Glucose Metabolism

It is known that obesity and/or physical inactivity greatly increase a person's risk of developing heart disease and other serious health problems. This is partly because diabetes is associated with inflammation, oxidative stress, and insulin resistance. Diabetes is also associated with high levels of triglycerides in the blood and tissues such as the liver (known as fatty liver or steatosis). This elevation of fat in the liver is known to cause liver insulin resistance and impair the function of the liver and this impairment contributes to the development of diabetes.

Studies have shown that both aerobic exercise and weight loss have beneficial results on insulin resistance. However, the cause of this benefit remains unclear. We know that both aerobic exercise and/or weight loss can improve how muscle responds to insulin. However, it is also known that aerobic exercise and/or weight loss lowers liver fat content, thereby making it possible that the liver's response to insulin is also improved by weight loss and/or exercise training. An improved responsiveness of the liver to insulin could lower blood sugar levels after a meal and it could also lower morning blood sugar levels. However, very little is known about how exercise and/or weight loss improves liver function in people with type 2 diabetes.

Hypothesis 1: Improved hepatic insulin sensitivity, as a result of either exercise training or weight loss, will increase the amount of glucose from an oral load that is taken up by the liver in subjects with DM. We also hypothesize that the amount of glucose taken up by the liver will be increased even further in response to exercise training plus weight loss compared to either treatment alone.

Hypothesis 2: Increases in hepatic insulin sensitivity as a result of exercise with weight loss will cause reductions in EGP during the fasted state, and will improve the suppression of EGP seen in response to hyperinsulinemia.