Acute treatment of ob/ob mice with S-carboxymethylated hGH (
RCM-hGH), a diabetogenic derivative of GH which lacks significant
insulin-like and growth-promoting activities, results in an increase in fasting plasma
insulin and
blood glucose levels and enhanced peripheral tissue
insulin resistance. Plasma
insulin level increases within 3 h after
RCM-hGH is administered, whereas increased
blood glucose concentration and enhanced peripheral tissue
insulin resistance became evident 6 h after the
hormone derivative is given. The lag period seen in the manifestation of these diabetogenic effects of
RCM-hGH is consistent with the time required for gene expression. Therefore, the present study was undertaken to determine whether the above acute responses to the diabetogenic action of
RCM-hGH would be expressed in ob/ob mice in which
protein synthesis was blocked with
cycloheximide. Female ob/ob mice were given either saline or
cycloheximide (0.1 mg/g BW) ip and 1 h later were fasted and treated with either saline or 200 micrograms
RCM-hGH ip. The mice were given a second injection of
cycloheximide during the middle of the
hormone treatment period to insure that
protein synthesis remained blocked for the entire 6 h. In the animals not receiving
cycloheximide, fasting plasma
insulin level and
blood glucose concentration were markedly elevated 6 h after the injection of
RCM-hGH. Also, the GH derivative attenuated the ability of
insulin added in vitro to stimulate
glucose oxidation by adipose tissue segments isolated from the animals.(ABSTRACT TRUNCATED AT 250 WORDS)