The contribution of different organs and tissues of the rat to assimilation of glucose

Pb, Curtis-Prior; Trethewey, John; Ga, Stewart; Hanley, T.

doi:10.1007/bf00427976

Cited by 46 publications

(23 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On a weight basis, skeletal muscle is the most important glucose-utilizing tissue [11]. In man, it has been demonstrated that skeletal muscles are primarily responsible for the disposal of an intravenous glucose toad in an euglycaemic clamp [12].…”

Section: Discussionmentioning

confidence: 99%

Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats

1991

View full text Add to dashboard Cite

Summary.Our previous work has suggested the presence of an insulin resistance in the adult offspring of streptozotocindiabetic pregnant rats. In this study we used the euglycaemic hyperinsulinaemic clamp technique with an isotope-dilution method to define and quantify this postulated insulin resistance in adult offspring of streptozotocin-diabetic rats. Under basal conditions, these rats had a lower body weight than control rats, but their glucose and insulin concentrations were normal. During the hyperinsulinaemic clamp, the steady-state glucose infusion rate was significantly lower in the offspring of streptozotocin-diabetic rats than in both ageand weight-matched controls, indicating insulin resistance. Basal peripheral tissue glucose utilization was normal in the offspring of streptozotocin-diabetic rats, but the dose-response curve was shifted to the right: insulin concentrations causing half-maximal stimulation of glucose utilization were increased by about 60% in the offspring of diabetic rats; the maximal stimulation of glucose utilization, however, was unaltered. Basal hepatic glucose production was normal, but again, half-maximal suppression of glucose production occurred at insulin concentrations 50% higher than in controt rats; in addition, the maximal suppression of glucose production was significantly decreased, even at insulin concentrations of 5700 btU/ml. These data are evidence for an insulin resistance in the adult offspring of streptozotocin-diabetic rats, characterized by: (1) a decreased insulin sensitivity by peripheral glucose-utilizing tissues, and, (2) a decreased sensitivity and responsiveness of the liver. Key words:Insulin resistance, euglycaemic hyperinsulinaemic clamp, offspring of streptozotocin-diabetic rats.Metabolic changes in the pregnant streptozotocindiabetic rat have been shown to affect fetal development and fetal glucose homeostasis [1, 21. A severe hyperglycaemia ( > 20 mmol/1) in the maternal rat results in hyperglycaemia and hypoinsulinaemia of their fetuses. On histology and electronmicroscopy, we found evidence of islet hypertrophy, Beta-cell hyperplasia and Beta-cell degranulation in these fetuses: a 'Beta-cell exhaustion phenomenon' is probably the cause of decreased insulin levels in fetal serum [1,2]. Malnutrition of the newborn rats by their mothers, causes frequent postnatal death and subnormal glucose and insulin levels in the survivors until weaning [1,3]. Body weight in the offspring of severely hyperglycaemic rats is significantly lower than normal from day 20 of gestation and it remains significantly lower during postnatal life: during the lactation period and after weaning [1][2][3]. The adult offspring of severely hyperglycaemic pregnant rats (SDF-rats) have a normal pancreas on histology and normal serum glucose and insulin concentrations in basal conditions, but their glucose tolerance is clearly impaired [3,4]. Data from an in vivo 123I-insulin captation study would suggest an insulin resistance in SDF-rats [5]. In this study, we used the euglycaemic ...

show abstract

Section: Discussionmentioning

confidence: 99%

Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats

1991

View full text Add to dashboard Cite

show abstract

“…4 B) again confirmed that the insulin-stimulated glycogen repletion was severely impaired in diabetic rats and was completely restored to normal by the treatment with vanadate, but not with phlorizin. Because muscle mass in the rat represents 40% of the body weight (43,45), it is possible to calculate the contribution of skeletal muscle glycogen synthesis to the whole body glucose uptake. In normal rats (group 1), 35% of the tissue glucose uptake (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The whole body muscle glycogenic rates displayed in this figure are obtained from the data shown in Fig. 4 B assuming that total body muscle mass in the rat is 40% of the body weight (43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

Correction of chronic hyperglycemia with vanadate, but not with phlorizin, normalizes in vivo glycogen repletion and in vitro glycogen synthase activity in diabetic skeletal muscle.

Rossetti¹,

Lauglin²

1989

J. Clin. Invest.

117

View full text Add to dashboard Cite

Vanadate has insulin-like activity in vitro and in vivo. To characterize the in vivo mechanism of action of vanadate, we examined meal tolerance, insulin-mediated glucose disposal, in vivo liver and muscle glycogen synthesis, and in vitro glycogen synthase activity in 90% partially pancreatectomized rats. Four groups were studied: group I, sham-operated controls; group II, diabetic rats; group III, diabetic rats treated with vanadate; and group IV, diabetic rats treated with phlorizin. Insulin sensitivity, assessed with the euglycemic hyperinsulinemic clamp technique in awake, unstressed rats, was reduced by -28% in diabetic rats. Both vanadate and phlorizin treatment completely normalized meal tolerance and insulin-mediated glucose disposal. Muscle glycogen synthesis was reduced by -80% in diabetic rats (P < 0.01) and was completely restored to normal by vanadate, but not by phlorizin treatment. Glycogen synthase activity was reduced in skeletal muscle of diabetic rats (P < 0.05) compared with controls and was increased to supranormal levels by vanadate treatment (P < 0.01). Phlorizin therapy did not reverse the defect in muscle glycogen synthase.These results suggest that (a) the defect in muscle glycogen synthesis is the major determinant of insulin resistance in diabetic rats; (b) both vanadate and phlorizin treatment normalize meal tolerance and insulin sensitivity in diabetic rats; (c) vanadate treatment specifically reverses the defect in muscle glycogen synthesis in diabetic rats. This effect cannot be attributed to the correction of hyperglycemia because phlorizin therapy had no direct influence on the glycogenic pathway.

show abstract

“…Skeletal muscles are important targets for insulin, since they are the major insulin-dependent peripheral tissue in the body. They represent 40 -50% of total body weight and contribute to 35% of glucose uptake in response to an intravenous glucose injection (33). Increased muscle weight and decreased fat depot weight probably contribute to the increased sensitivity to insulin and increased muscle glucose uptake in LPS-treated rats.…”

Section: Control Lpsmentioning

confidence: 99%

Postnatal endotoxin exposure results in increased insulin sensitivity and altered activity of neuroendocrine axes in adult female rats

Nilsson

Jennische

et al. 2002

European Journal of Endocrinology

View full text Add to dashboard Cite

Objectives: Severe postnatal infection leads to a systemic inflammatory response with release of cytokines and glucocorticoids, representing a stressful event for the newborn child. The purpose of this study was to mimic this situation and to study the effects of early postnatal endotoxin exposure of female rat pups on metabolic, endocrine and anthropometric variables in adulthood. Design: Female pups were given subcutaneous injections of lipopolysaccharides (LPS; Salmonella enteriditis, 0.05 mg/kg) or vehicle 3 and 5 days after birth. Results: Six hours after injection, LPS-treated rats had higher corticosterone levels than controls. As adults, LPS-exposed female rats showed increased insulin sensitivity ðP , 0:05Þ; measured with the hyperinsulinemic euglycemic clamp (5 mU/kg per min). They exhibited a higher locomotor activity ðP , 0:05Þ and increased skeletal muscle mass in comparison with controls ðP , 0:05Þ: Basal ACTH and corticosterone levels in LPS-treated rats were elevated ðP , 0:05Þ; as were corticosterone levels after exposure to a novel environment stress ðP , 0:05Þ: The adrenals were morphologically changed and enlarged ðP , 0:05Þ in LPS-exposed rats at 11 weeks of age, and a higher density of hypothalamic but not hippocampal glucocorticoid receptor protein was found in the LPS-treated rats ðP , 0:05Þ: Furthermore, circulating progesterone levels were lower ðP , 0:05Þ and testosterone tended to be higher. Conclusion:The results indicate that postnatal exposure to LPS leads to increased insulin sensitivity in the adult female rat. In addition, LPS-treated rats showed changes in the regulation of hypothalamicpituitary -adrenal and hypothalamic -pituitary -gonadal axes. This study suggests that postnatal exposure to an endotoxin such as LPS can induce specific programming of neuroendocrine regulation, with long-term consequences in adult life.

show abstract

The contribution of different organs and tissues of the rat to assimilation of glucose

Cited by 46 publications

References 10 publications

Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats

Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats

Correction of chronic hyperglycemia with vanadate, but not with phlorizin, normalizes in vivo glycogen repletion and in vitro glycogen synthase activity in diabetic skeletal muscle.

Postnatal endotoxin exposure results in increased insulin sensitivity and altered activity of neuroendocrine axes in adult female rats

Contact Info

Product

Resources

About