Effects of various insulin dosages on hepatic lipogenesis

Insulin treatment of diabetic rats fed a high-carbohydrate, fat-free diet produces a dramatic accumulation of hepatic lipids. However, this increase in hepatic lipids may only be a response to injections of exceptionally high doses of insulin. This study addresses this possibility. Alloxan-diabetic rats, fed a high-carbohydrate, fat-free diet, were given insulin every 12 h for 60 h at the following dosages: 1/2 unit each, 1 unit each, 2 units each, and 4 units each of regular and NPH insulins. At the end of the treatment period, liver samples were collected and used for morphological and biochemical analyses. Histologic examination revealed hepatic lipid accumulations at all insulin doses; the amount of lipid increased until maximal levels were reached at an insulin dosage of 1 + 1, which was maintained at doses of 2 + 2 and 4 + 4. Thus, hepatic lipid accumulation occurs regardless of the dosage of insulin administered to the diabetic animal. It is not simply an abnormal cellular response to excessive hormone levels. Similarly, the activity of the hepatic lipogenic enzyme, malic enzyme, increased at initial insulin dosages and reached maximal levels at 2 + 2. However, in contrast to lipid accumulation, enzyme activity decreased at the final insulin dosage of 4 + 4. Thus, there appears to be a direct relationship between increasing insulin levels and malic enzyme activity until an optimal insulin concentration is reached. After this point, excessive insulin levels do inhibit malic enzyme activity.