Chronic treatment of ob/ob mice with
growth hormone (GH) increases plasma
insulin and
blood glucose concentrations, and enhances
insulin resistance in peripheral tissues. The purpose of the present study was: (1) to determine the length of time required for the development of increased circulating
insulin concentration and adipose tissue
insulin resistance in response to GH in the ob/ob mouse, (2) to examine the relationship between the rise in
insulin concentration and the development of
insulin resistance, and (3) to test whether the
hormone derivative could enhance
insulin resistance in isolated adipose tissue when added in vitro. Female ob/ob mice were injected intraperitoneally (ip) with either saline or 200 micrograms of S-carboxymethylated human GH (
RCM-hGH), a diabetogenic GH derivative, which lacks significant insulinlike or growth-promoting activities. A threefold increase in plasma
insulin concentration was observed three and six hours after
RCM-hGH injection, but increased
hyperglycemia was evident only after six hours. The in vitro stimulatory effect of
insulin on [14C]
glucose oxidation by parametrial adipose tissue was unchanged at three hours but suppressed six hours following administration of
RCM-hGH. When the plasma
insulin level of ob/ob mice was increased threefold by the administration of neutral
protamine Hagedorn (
NPH) insulin, the in vitro stimulatory effect of
insulin on [14C]
glucose oxidation by adipose tissue isolated from these animals was not altered, suggesting that
insulin-induced receptor or postreceptor changes do not account for the increased
insulin resistance produced by
RCM-hGH.(ABSTRACT TRUNCATED AT 250 WORDS)