Effects of Insulin on Glucose Metabolism and Glucose Transport in Fat Cells of Hormone-Treated Hypophysectomized Rats: Evidence That Growth Hormone Restricts Glucose Transport*

Abstract

In earlier studies we have shown that insulin does not stimulate glucose incorporation in adipocytes of hypophysectomized (hypox) rats. Basal glucose incorporation is decreased, although basal 3-O-methylglycose transport is very rapid and cannot be further stimulated by insulin. In this study we treated hypox rats with human GH, ACTH, and T3, alone or in combination, and examined the effects of insulin on glucose incorporation into fat cells and on 3-O-methylglucose transport. The results show that chronic administration of T3 alone to hypox rats partially restores glucose incorporation into fat cells and, in combination with ACTH, completely restores this incorporation. The two hormones have no effect on the glucose carrier system. The transport rate under T3 and ACTH replacement therapy continues to proceed at a maximal rate, so that basal glucose incorporation is high but not further enhanced by insulin. In contrast, administration of human GH to hypox rats does not influence glucose incorporation but has a marked effect on glucose transport. The basal glucose transport rate returns toward normal and again responds to insulin. This suggests 1) that enzyme activities responsible for the lipogenetic capacity of the fat cell are decreased in hypox rats and returned toward normal by the combined T3/ACTH treatment, and 2) that the limitation of glucose transport in the fat cell is controlled by GH. GH seems to induce a change of the glucose-carrier system; it leads to a restriction of glucose transport, which is acutely modulated by insulin.

Effect of insulin on glucose transport and metabolism in adipose tissue and skeletal muscle of hypophysectomized rats

“…Fig.1 demonstrates that 3-O-methylglucose efflux from isolated fat pads of hypox rats proceeds at a maximal rate and is not further stimulated by insulin. This finding confirms earlier observations in isolated adipocytes [1,2] and extends them to the intact tissue. The lower panel of fig.1 shows that the above finding does not apply to skeletal muscle.…”

“…In contrast to adipose tissue, the glucose carrier system of skeletal muscle does not seem to be under the regulatory influence of the pituitary hormones. In adipocytes, a glucose transport-limiting factor has been postulated [2,7], which restricts glucose transport in the basal state and which is itself inhibited by the action of insulin thus giving rise to increased glucose entry into the fat cell. The limiting cofactor has been shown to be decreased or absent in adipocytes from hypox rats and to be induced by growth hormone treatment of the animals [2].…”

“…In adipocytes, a glucose transport-limiting factor has been postulated [2,7], which restricts glucose transport in the basal state and which is itself inhibited by the action of insulin thus giving rise to increased glucose entry into the fat cell. The limiting cofactor has been shown to be decreased or absent in adipocytes from hypox rats and to be induced by growth hormone treatment of the animals [2]. If, in analogy to adipose tissue, a glucose transport-limiting factor is present in skeletal muscle it must underly a completely different mode of regulation and possess different molecular characteristics.…”

“…If, in analogy to adipose tissue, a glucose transport-limiting factor is present in skeletal muscle it must underly a completely different mode of regulation and possess different molecular characteristics. In adipocytes [1,2] and intact adipose tissue [1] formation of lipids from glucose and glucose oxidation are similar for normal and hypox rats despite the highly increased glucose transport rate in the latter. Insulin barely stimulates glucose utilization in adipocytes or intact adipose tissue of hypox animals [1,2].…”

“…Growth hormone treatment of hypox rats for several days restores glucose transport in the adipocytes towards normal and also restores insulin sensitivity of the glucose carrier system and of glucose metabolism [2]. These findings raised the following question: Are similar alterations encountered in other classicial insulin target organs, such as skeletal muscle, or are they tissue-specific, i.e., characteristic for the adipocyte?…”