Glucose Utilization Rates and Insulin Sensitivity In Vivo in Tissues of Virgin and Pregnant Rats

Abstract

In vivo studies have shown that insulin resistance in late pregnancy results from a decreased sensitivity of liver and peripheral tissues. In the present study, measurements of the rates of glucose utilization by skeletal muscles (soleus, extensor digitorum longus, epitrochlearis, and diaphragm), white adipose tissue, and brain of virgin and 19-day pregnant rats were performed in the basal condition and during a euglycemic, hyperinsulinemic (400 microU/ml) clamp to quantify the partition of glucose utilization and to identify the tissues other than liver responsible for insulin resistance. Fetal and placental glucose utilization rates were also measured in pregnant rats. The fetal glucose utilization rate (22 mg/min/kg) was very high and was not stimulated by physiologic maternal hyperinsulinemia. By contrast, the placental glucose utilization rate (29 mg/min/kg) was increased by 30% during hyperinsulinemia. The glucose utilization rate of the conceptus represented 23% of the maternal glucose utilization rate in the basal state. Glucose utilization rates in the basal condition were not statistically altered by pregnancy in brain, skeletal muscles, and white adipose tissue. During hyperinsulinemia (400 microU/ml), glucose utilization rates in extensor digitorum longus, epitrochlearis, and white adipose tissue were 30-70% lower in pregnant than in virgin rats. Insulin sensitivity of glucose metabolism in all the tissues tested other than brain was 50% lower in pregnant than in virgin rats. We conclude that skeletal muscles and, to a smaller extent, adipose tissue are involved in the insulin resistance of late pregnancy.

Defects in insulin signal transduction in liver and muscle of pregnant rats

“…In vivo studies have shown that pregnant rats become progressively resistant to insulin after day 16 of gestation [5]. In these animals, the insulin resistance of skeletal muscle has been clearly demonstrated in vitro, while the insulin resistance in vivo in peripheral tissues and liver has been substantiated in studies using the euglycaemic-hyperinsulinaemic clamp technique [6,7].Insulin initiates its metabolic and growth-promoting effects by binding to the a subunit of its tetrameric receptor, thereby activating the kinase in the b subunit [8]. This interaction catalyses the intramolecular autophosphorylation of specific tyrosine residues of the b subunit which further enhances the tyrosine kinase activity of the receptor toward other protein substrates [8].…”

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Insulin resistance during pregnancy has been reported both in women and in experimental animals [1][2][3][4][5][6][7], but the mechanism of this resistance remains unclear. In vivo studies have shown that pregnant rats become progressively resistant to insulin after day 16 of gestation [5].

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Hyperthyroidism impairs pancreatic beta cell adaptations to late pregnancy and maternal liporegulation in the rat

“…Inadequate compensatory hypersecretion of insulin to counter insulin resistance is critical to the pathology of type 2 diabetes [3]. Pregnancy is a progressive state of maternal insulin resistance [4][5][6] (reviewed in [7]), which in healthy pregnancies is accompanied by reciprocal increases in insulin secretion (see [5,8]). Gestational diabetes occurs in women who secrete insufficient insulin to compensate for lowered in-sulin sensitivity during the third trimester [9] (reviewed in [3]).…”

Decreased contraction-stimulated glucose transport in isolated epitrochlearis muscles of pregnant rats

“…The similar relative decline in insulin-and contraction-stimulated glucose transport raises the possibility that pregnancy impairs a distal process that is common to mechanisms whereby each stimulus activates glucose transport. insulin resistance; gestational diabetes; fatigue; glycogen LATE PREGNANCY (gestational days 18 -22 in the rat, third trimester in humans) is characterized by whole body insulin resistance (8,27). Insulin-stimulated glucose disposal by skeletal muscle during a euglycemic-hyperinsulinemic clamp is reduced in pregnant compared with nonpregnant rats (27).…”

“…insulin resistance; gestational diabetes; fatigue; glycogen LATE PREGNANCY (gestational days 18 -22 in the rat, third trimester in humans) is characterized by whole body insulin resistance (8,27). Insulin-stimulated glucose disposal by skeletal muscle during a euglycemic-hyperinsulinemic clamp is reduced in pregnant compared with nonpregnant rats (27). Insulin resistance is also a normal characteristic of late pregnancy in humans, presumably to ensure adequate availability of maternal nutrients to the fetus during this period of rapid growth (5,25).…”