Long-Term Regulation of Adipocyte Glucose Transport Capacity by Circulating Insulin in Rats

The effects of chronic insulin administration on the metabolism of isolated adipose cells and muscle were studied. Adipose cells from 2 and 6 wk insulin-treated and control rats, fed either chow or chow plus sucrose, were prepared, and insulin binding, 3-0-methylglucose transport, glucose metabolism, and lipolysis were measured at various insulin concentrations. After 2 wk of treatment, adipose cell size and basal glucose transport and metabolism were unaltered, but insulin-stimulated transport and glucose metabolism were increased two-to threefold when cells were incubated in either 0.1 mM glucose (transport rate limiting) or 10 mM glucose (maximum glucose metabolism). Insulin binding was increased by 30%, but no shift in the insulin dose-response curve for transport or metabolism occurred. After 6 wk of treatment, the effects of hyperinsulinemia on insulin binding and glucose metabolism persisted and were superimposed on the changes in cell function that occurred with increasing cell size in aging rats. Hyperinsulinemia for 2 or 6 wk did not alter basal or epinephrine-stimulated lipolysis in adipose cells or the antilipolytic effect of insulin. In incubated soleus muscle strips, insulin-stimulated glucose metabolism was significantly increased after 2 wk of hyperinsulinemia, but these increases were not observed after 6 wk of treatment. We conclude that 2 wk of continuous hyperinsulinemia results in increased insulin-stimulated glucose metabolism in both adipose cells and soleus muscle. Despite increased insulin binding to adipose cells, no changes in insulin sensitivity were observed in adipose cells or muscle. In adipose cells, the increased glucose utilization resulted from both increased transport (2 wk only) and intracellular glucose metabolism (2 and 6 wk). In muscle, after 2 wk of treatment, both glycogen synthesis and total glucose metabolism were increased. These effects of hyperinsulinemia were lost in muscle after 6 wk of treatment, when compared with sucrose-supplemented controls.

Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of glucose utilization in adipose cells and muscle after long-term experimental hyperinsulinemia in rats.

Wardzala¹,

Hirshman²,

Pofcher³

et al. 1985

“…4). Despite the (17)(18)(19)(20). Values for apparent Vmax were significantly higher (P < 0.02), however, in T3-treated (3.91±0.25 ,umol/109 cells per 10 min) than in control (3.45±0.28 ,umol/109 cells per 10 min) groups.…”

Section: Resultsmentioning

confidence: 87%

Stimulation by Triiodothyronine of the In Vitro Uptake of Sugars by Rat Thymocytes

Segal¹,

Ingbar²

1979

A B S T R A C T Studies were conducted to ascertain the in vitro effect of 3,5,3'-triiodothyronine (T3) on the accumulation of the glucose analogue, 2-deoxyglucose (2-DG), by thymocytes freshly isolated from weanling rats. At a concentration of 1 ,uM, T3 stimulated the 15-min uptake of 3H-2-DG after cells had been exposed to T3 for only 30 min. Significant stimulation of 2-DG accumulation was produced by 1 nM T3, with increasing stimulation at doses ranging up to 10 ,uM. T3 did not alter the fraction of accumulated 2-DG that was phosphorylated, and kinetic studies indicated that its effect was associated with a significant increase in the apparent Vmax of 2-DG accumulation, but not the apparent Km. T3 also enhanced the accumulation by thymocytes of the nonmetabolized glucose analogue, 3-0-methylglucose (3-0-MG), an effect that was evidently the result of an increase in 3-0-MG transport into the cell, because it was seen in cells incubated with 3H-3-O-MG for only 30 s. The proportionate increase in 2-DG accumulation produced by T3 was not altered by preincubating cells with concentrations of puromycin or cycloheximide sufficient to reduce [3H]-leucine incorporation by 95%, and T3 over a period of >2 h had no effect on [3H]leucine incorporation itself.These results indicate that T3 stimulates the uptake of sugars in rat thymocytes in vitro by an effect on their inward transport. The promptness of the effect and its failure to be inhibited during profound inhibition of protein synthesis further indicate that this effect of T3 is not mediated through a nuclear-dependent mechanism. Rather, the properties of this response, and of the increases in amino acid and 2-DG accumulation produced by T3 in other tissue preparations, strongly suggest that these effects of T3 are mediated at the level of cell membrane.

“…Adipocytes from insulininfused, hypoglycemic animals had a similarly increased total glucose transporter number by cytochalasin B binding (22) and also increased insulin-stimulated glucose uptake in vitro (22)(23)(24). The findings of Wardzala et al (23) that soleus muscle strips from insulin-infused rats have enhanced insulinstimulated glucose metabolism and glycogen synthase activity suggest that muscle may have similarly enhanced insulin-stimulated glucose disposal in vitro.…”

Section: Introductionmentioning

confidence: 99%

Effects of altered glucose homeostasis on glucose transporter expression in skeletal muscle of the rat.

Bourey

Korányi²,

James³

et al. 1990

Previous studies have suggested that alteration in the expression of the insulin-regulatable glucose transporter of muscle (GLUT4 protein) may be an important determinant of insulin action. In the present studies, we have examined GLUT4 mRNA and protein concentrations in muscle after variations in the metabolic status of the intact animal (i.e., 7 d streptozotocin-induced diabetes, 7 d insulin-induced hypoglycemia, and 3 d fasting). These changes in glucose homeostasis were associated with the following changes in GLUT-4 gene products: a decrease of 30% in both mRNA and protein with diabetes; a 50% increase in mRNA and a 2.4-fold increase in protein with insulin injection; and normal mRNA in spite of a 2.7-fold increase in protein with fasting. Fasted diabetics exhibited an increase of 50% in GLUT4 mRNA and a 2.4-fold increase in protein relative to fed diabetics. In diabetic and insulin-injected groups, the changes in GLUT-4 protein were similar to changes in mRNA, but in fasting, GLUT-4 protein increased without a concomitant change in mRNA. Overall there was no correlation between muscle concentrations of GLUT4 protein and mRNA. Muscle GLUT4 protein concentration tended to correlate with plasma glucose (r = -0.57, P < 0.001), but not with plasma insulin. These results indicate that (a) chronic changes in glucose homeostasis are associated with changes in expression of GLUT4 protein in muscle; (b) GLUT-4 protein increased in fasted soleus muscle without change in mRNA, thereby differing from fasted adipocytes in which both GLUT4 products diminish; and (c) no simple relationship exists between total muscle GLUT-4 protein content and whole-body insulin sensitivity. (J. Clin. Invest. 1990. 86:542-547.)