The Experts below are selected from a list of 258 Experts worldwide ranked by ideXlab platform
Laurie J Goodyear - One of the best experts on this subject based on the ideXlab platform.
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Effects of Streptozocin-induced diabetes and islet cell transplantation on insulin signaling in rat skeletal muscle.
Endocrinology, 1999Co-Authors: Jeffrey F. Markuns, Michael F Hirshman, R. Napoli, A M Davalli, Bentley Cheatham, Laurie J GoodyearAbstract:Streptozocin-induced diabetes is associated with alterations in insulin signaling in rat skeletal muscle, including increased insulin receptor substrate-1 phosphorylation and phosphotidylinositol 3-kinase activity. In the current study, we determined the effects of Streptozocin-induced diabetes and treatment of diabetes by islet cell transplantation on several proximal insulin-activated signaling proteins. Three groups of male Lewis rats (untreated Streptozocin-diabetic animals, islet cell-transplanted diabetic rats, and nondiabetic control rats) were studied in the basal state or 30 min after i.p. insulin injection (20 U/rat). Mixed hindlimb skeletal muscle lysates were used to determine the expression and enzymatic activities of the extracellular regulated kinase 2 (ERK2), p90 ribosomal S6 kinase (RSK2), Akt, and p70 S6 kinase (p70S6k). In all three groups of rats, insulin significantly increased ERK2, RSK2, Akt, and p70S6k activities. There was no effect of diabetes on insulin-stimulated ERK2 activity or ERK2 protein levels. RSK2 expression and insulin-stimulated RSK2 activity were significantly elevated in diabetic rats compared with those in the control animals. Insulin-stimulated Akt activity was also significantly greater in the diabetic animals, but there was no change in protein expression. In contrast, there was a decrease in insulin-stimulated p70S6k activity with no change in protein expression in the diabetic rats. Islet transplantation partially (RSK2) or fully (Akt, p70S6k) normalized these diabetes-induced changes in insulin signaling proteins. We conclude that Streptozocin diabetes results in the dysregulation of several critical insulin-activated proteins in rat skeletal muscle, but islet cell transplantation is an effective therapy to partially correct these alterations in insulin signaling.
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Effects of Streptozocin-Induced Diabetes and Islet Cell Transplantation on Insulin Signaling in Rat Skeletal Muscle*This work was supported by NIH-NIAMS Grant AR-42238 (to L.J.G.).
Endocrinology, 1999Co-Authors: Jeffrey F. Markuns, Michael F Hirshman, R. Napoli, A M Davalli, Bentley Cheatham, Laurie J GoodyearAbstract:Streptozocin-induced diabetes is associated with alterations in insulin signaling in rat skeletal muscle, including increased insulin receptor substrate-1 phosphorylation and phosphotidylinositol 3-kinase activity. In the current study, we determined the effects of Streptozocin-induced diabetes and treatment of diabetes by islet cell transplantation on several proximal insulin-activated signaling proteins. Three groups of male Lewis rats (untreated Streptozocin-diabetic animals, islet cell-transplanted diabetic rats, and nondiabetic control rats) were studied in the basal state or 30 min after i.p. insulin injection (20 U/rat). Mixed hindlimb skeletal muscle lysates were used to determine the expression and enzymatic activities of the extracellular regulated kinase 2 (ERK2), p90 ribosomal S6 kinase (RSK2), Akt, and p70 S6 kinase (p70S6k). In all three groups of rats, insulin significantly increased ERK2, RSK2, Akt, and p70S6k activities. There was no effect of diabetes on insulin-stimulated ERK2 activity or ERK2 protein levels. RSK2 expression and insulin-stimulated RSK2 activity were significantly elevated in diabetic rats compared with those in the control animals. Insulin-stimulated Akt activity was also significantly greater in the diabetic animals, but there was no change in protein expression. In contrast, there was a decrease in insulin-stimulated p70S6k activity with no change in protein expression in the diabetic rats. Islet transplantation partially (RSK2) or fully (Akt, p70S6k) normalized these diabetes-induced changes in insulin signaling proteins. We conclude that Streptozocin diabetes results in the dysregulation of several critical insulin-activated proteins in rat skeletal muscle, but islet cell transplantation is an effective therapy to partially correct these alterations in insulin signaling.
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Exercise training normalizes glucose metabolism in a rat model of impaired glucose tolerance.
Metabolism-clinical and Experimental, 1991Co-Authors: Laurie J Goodyear, E. D. Horton, Sonja M. Knutson, L. J. Wardzala, Michael F Hirshman, Edward S HortonAbstract:Abstract The purpose of this study was to characterize an animal model of impaired glucose tolerance produced by Streptozocin treatment of rats (45 mg/kg, intravenously [IV]) and selection of animals with plasma glucose concentrations less than 150 mg/dL. In addition, we determined the effects of physical training on glucose tolerance and metabolism in these animals. During 10 weeks of monitoring, it was determined that these animals have nearly normal plasma glucose concentrations; however, they have an impaired glucose tolerance when challenged with an oral glucose load. They also have normal fasting insulin, free fatty acid, and triglyceride concentrations, normal body weight and food consumption patterns, and normal rates of skeletal muscle glucose uptake, but impaired basal and insulin-stimulated glucose metabolism in isolated adipose cells. Ten weeks of exercise training normalized both the impaired glucose tolerance and adipose cell function present in the untrained Streptozocin-treated rats. Low-dose Streptozocin treatment of rats with appropriate selection of animals based on plasma glucose concentrations appears to be an excellent model of impaired glucose tolerance for studies of factors affecting insulin resistance and altered glucose metabolism.
David Klaassen - One of the best experts on this subject based on the ideXlab platform.
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Streptozocin–Doxorubicin, Streptozocin–Fluorouracil, or Chlorozotocin in the Treatment of Advanced Islet-Cell Carcinoma
The New England journal of medicine, 1992Co-Authors: Charles G. Moertel, Myrto Lefkopoulo, Stuart R. Lipsitz, Richard G. Hahn, David KlaassenAbstract:Abstract Background. The combination of Streptozocin and fluorouracil has become the standard therapy for advanced islet-cell carcinoma. However, doxorubicin has also been shown to be active against this type of tumor, as has chlorozotocin, a drug that is structurally similar to Streptozocin but less frequently causes vomiting. Methods. In this multicenter trial, we randomly assigned 105 patients with advanced islet-cell carcinoma to receive one of three treatment regimens: Streptozocin plus fluorouracil, Streptozocin plus doxorubicin, or chlorozotocin alone. The 31 patients in whom the disease did not respond to treatment were crossed over to chlorozotocin alone or to one of the combination regimens. Results. Streptozocin plus doxorubicin was superior to Streptozocin plus fluorouracil in terms of the rate of tumor regression, measured objectively (69 percent vs. 45 percent, P = 0.05), and the length of time to tumor progression (median, 20 vs. 6.9 months; P = 0.001). Streptozocin plus doxorubicin also ha...
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Streptozocin doxorubicin Streptozocin fluorouracil or chlorozotocin in the treatment of advanced islet cell carcinoma
The New England Journal of Medicine, 1992Co-Authors: Charles G. Moertel, Myrto Lefkopoulo, Stuart R. Lipsitz, Richard G. Hahn, David KlaassenAbstract:Abstract Background. The combination of Streptozocin and fluorouracil has become the standard therapy for advanced islet-cell carcinoma. However, doxorubicin has also been shown to be active against this type of tumor, as has chlorozotocin, a drug that is structurally similar to Streptozocin but less frequently causes vomiting. Methods. In this multicenter trial, we randomly assigned 105 patients with advanced islet-cell carcinoma to receive one of three treatment regimens: Streptozocin plus fluorouracil, Streptozocin plus doxorubicin, or chlorozotocin alone. The 31 patients in whom the disease did not respond to treatment were crossed over to chlorozotocin alone or to one of the combination regimens. Results. Streptozocin plus doxorubicin was superior to Streptozocin plus fluorouracil in terms of the rate of tumor regression, measured objectively (69 percent vs. 45 percent, P = 0.05), and the length of time to tumor progression (median, 20 vs. 6.9 months; P = 0.001). Streptozocin plus doxorubicin also ha...
Michael F Hirshman - One of the best experts on this subject based on the ideXlab platform.
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Effects of Streptozocin-induced diabetes and islet cell transplantation on insulin signaling in rat skeletal muscle.
Endocrinology, 1999Co-Authors: Jeffrey F. Markuns, Michael F Hirshman, R. Napoli, A M Davalli, Bentley Cheatham, Laurie J GoodyearAbstract:Streptozocin-induced diabetes is associated with alterations in insulin signaling in rat skeletal muscle, including increased insulin receptor substrate-1 phosphorylation and phosphotidylinositol 3-kinase activity. In the current study, we determined the effects of Streptozocin-induced diabetes and treatment of diabetes by islet cell transplantation on several proximal insulin-activated signaling proteins. Three groups of male Lewis rats (untreated Streptozocin-diabetic animals, islet cell-transplanted diabetic rats, and nondiabetic control rats) were studied in the basal state or 30 min after i.p. insulin injection (20 U/rat). Mixed hindlimb skeletal muscle lysates were used to determine the expression and enzymatic activities of the extracellular regulated kinase 2 (ERK2), p90 ribosomal S6 kinase (RSK2), Akt, and p70 S6 kinase (p70S6k). In all three groups of rats, insulin significantly increased ERK2, RSK2, Akt, and p70S6k activities. There was no effect of diabetes on insulin-stimulated ERK2 activity or ERK2 protein levels. RSK2 expression and insulin-stimulated RSK2 activity were significantly elevated in diabetic rats compared with those in the control animals. Insulin-stimulated Akt activity was also significantly greater in the diabetic animals, but there was no change in protein expression. In contrast, there was a decrease in insulin-stimulated p70S6k activity with no change in protein expression in the diabetic rats. Islet transplantation partially (RSK2) or fully (Akt, p70S6k) normalized these diabetes-induced changes in insulin signaling proteins. We conclude that Streptozocin diabetes results in the dysregulation of several critical insulin-activated proteins in rat skeletal muscle, but islet cell transplantation is an effective therapy to partially correct these alterations in insulin signaling.
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Effects of Streptozocin-Induced Diabetes and Islet Cell Transplantation on Insulin Signaling in Rat Skeletal Muscle*This work was supported by NIH-NIAMS Grant AR-42238 (to L.J.G.).
Endocrinology, 1999Co-Authors: Jeffrey F. Markuns, Michael F Hirshman, R. Napoli, A M Davalli, Bentley Cheatham, Laurie J GoodyearAbstract:Streptozocin-induced diabetes is associated with alterations in insulin signaling in rat skeletal muscle, including increased insulin receptor substrate-1 phosphorylation and phosphotidylinositol 3-kinase activity. In the current study, we determined the effects of Streptozocin-induced diabetes and treatment of diabetes by islet cell transplantation on several proximal insulin-activated signaling proteins. Three groups of male Lewis rats (untreated Streptozocin-diabetic animals, islet cell-transplanted diabetic rats, and nondiabetic control rats) were studied in the basal state or 30 min after i.p. insulin injection (20 U/rat). Mixed hindlimb skeletal muscle lysates were used to determine the expression and enzymatic activities of the extracellular regulated kinase 2 (ERK2), p90 ribosomal S6 kinase (RSK2), Akt, and p70 S6 kinase (p70S6k). In all three groups of rats, insulin significantly increased ERK2, RSK2, Akt, and p70S6k activities. There was no effect of diabetes on insulin-stimulated ERK2 activity or ERK2 protein levels. RSK2 expression and insulin-stimulated RSK2 activity were significantly elevated in diabetic rats compared with those in the control animals. Insulin-stimulated Akt activity was also significantly greater in the diabetic animals, but there was no change in protein expression. In contrast, there was a decrease in insulin-stimulated p70S6k activity with no change in protein expression in the diabetic rats. Islet transplantation partially (RSK2) or fully (Akt, p70S6k) normalized these diabetes-induced changes in insulin signaling proteins. We conclude that Streptozocin diabetes results in the dysregulation of several critical insulin-activated proteins in rat skeletal muscle, but islet cell transplantation is an effective therapy to partially correct these alterations in insulin signaling.
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Exercise training normalizes glucose metabolism in a rat model of impaired glucose tolerance.
Metabolism-clinical and Experimental, 1991Co-Authors: Laurie J Goodyear, E. D. Horton, Sonja M. Knutson, L. J. Wardzala, Michael F Hirshman, Edward S HortonAbstract:Abstract The purpose of this study was to characterize an animal model of impaired glucose tolerance produced by Streptozocin treatment of rats (45 mg/kg, intravenously [IV]) and selection of animals with plasma glucose concentrations less than 150 mg/dL. In addition, we determined the effects of physical training on glucose tolerance and metabolism in these animals. During 10 weeks of monitoring, it was determined that these animals have nearly normal plasma glucose concentrations; however, they have an impaired glucose tolerance when challenged with an oral glucose load. They also have normal fasting insulin, free fatty acid, and triglyceride concentrations, normal body weight and food consumption patterns, and normal rates of skeletal muscle glucose uptake, but impaired basal and insulin-stimulated glucose metabolism in isolated adipose cells. Ten weeks of exercise training normalized both the impaired glucose tolerance and adipose cell function present in the untrained Streptozocin-treated rats. Low-dose Streptozocin treatment of rats with appropriate selection of animals based on plasma glucose concentrations appears to be an excellent model of impaired glucose tolerance for studies of factors affecting insulin resistance and altered glucose metabolism.
Jeffrey F. Markuns - One of the best experts on this subject based on the ideXlab platform.
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Effects of Streptozocin-Induced Diabetes and Islet Cell Transplantation on Insulin Signaling in Rat Skeletal Muscle*This work was supported by NIH-NIAMS Grant AR-42238 (to L.J.G.).
Endocrinology, 1999Co-Authors: Jeffrey F. Markuns, Michael F Hirshman, R. Napoli, A M Davalli, Bentley Cheatham, Laurie J GoodyearAbstract:Streptozocin-induced diabetes is associated with alterations in insulin signaling in rat skeletal muscle, including increased insulin receptor substrate-1 phosphorylation and phosphotidylinositol 3-kinase activity. In the current study, we determined the effects of Streptozocin-induced diabetes and treatment of diabetes by islet cell transplantation on several proximal insulin-activated signaling proteins. Three groups of male Lewis rats (untreated Streptozocin-diabetic animals, islet cell-transplanted diabetic rats, and nondiabetic control rats) were studied in the basal state or 30 min after i.p. insulin injection (20 U/rat). Mixed hindlimb skeletal muscle lysates were used to determine the expression and enzymatic activities of the extracellular regulated kinase 2 (ERK2), p90 ribosomal S6 kinase (RSK2), Akt, and p70 S6 kinase (p70S6k). In all three groups of rats, insulin significantly increased ERK2, RSK2, Akt, and p70S6k activities. There was no effect of diabetes on insulin-stimulated ERK2 activity or ERK2 protein levels. RSK2 expression and insulin-stimulated RSK2 activity were significantly elevated in diabetic rats compared with those in the control animals. Insulin-stimulated Akt activity was also significantly greater in the diabetic animals, but there was no change in protein expression. In contrast, there was a decrease in insulin-stimulated p70S6k activity with no change in protein expression in the diabetic rats. Islet transplantation partially (RSK2) or fully (Akt, p70S6k) normalized these diabetes-induced changes in insulin signaling proteins. We conclude that Streptozocin diabetes results in the dysregulation of several critical insulin-activated proteins in rat skeletal muscle, but islet cell transplantation is an effective therapy to partially correct these alterations in insulin signaling.
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Effects of Streptozocin-induced diabetes and islet cell transplantation on insulin signaling in rat skeletal muscle.
Endocrinology, 1999Co-Authors: Jeffrey F. Markuns, Michael F Hirshman, R. Napoli, A M Davalli, Bentley Cheatham, Laurie J GoodyearAbstract:Streptozocin-induced diabetes is associated with alterations in insulin signaling in rat skeletal muscle, including increased insulin receptor substrate-1 phosphorylation and phosphotidylinositol 3-kinase activity. In the current study, we determined the effects of Streptozocin-induced diabetes and treatment of diabetes by islet cell transplantation on several proximal insulin-activated signaling proteins. Three groups of male Lewis rats (untreated Streptozocin-diabetic animals, islet cell-transplanted diabetic rats, and nondiabetic control rats) were studied in the basal state or 30 min after i.p. insulin injection (20 U/rat). Mixed hindlimb skeletal muscle lysates were used to determine the expression and enzymatic activities of the extracellular regulated kinase 2 (ERK2), p90 ribosomal S6 kinase (RSK2), Akt, and p70 S6 kinase (p70S6k). In all three groups of rats, insulin significantly increased ERK2, RSK2, Akt, and p70S6k activities. There was no effect of diabetes on insulin-stimulated ERK2 activity or ERK2 protein levels. RSK2 expression and insulin-stimulated RSK2 activity were significantly elevated in diabetic rats compared with those in the control animals. Insulin-stimulated Akt activity was also significantly greater in the diabetic animals, but there was no change in protein expression. In contrast, there was a decrease in insulin-stimulated p70S6k activity with no change in protein expression in the diabetic rats. Islet transplantation partially (RSK2) or fully (Akt, p70S6k) normalized these diabetes-induced changes in insulin signaling proteins. We conclude that Streptozocin diabetes results in the dysregulation of several critical insulin-activated proteins in rat skeletal muscle, but islet cell transplantation is an effective therapy to partially correct these alterations in insulin signaling.
Charles G. Moertel - One of the best experts on this subject based on the ideXlab platform.
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Streptozocin–Doxorubicin, Streptozocin–Fluorouracil, or Chlorozotocin in the Treatment of Advanced Islet-Cell Carcinoma
The New England journal of medicine, 1992Co-Authors: Charles G. Moertel, Myrto Lefkopoulo, Stuart R. Lipsitz, Richard G. Hahn, David KlaassenAbstract:Abstract Background. The combination of Streptozocin and fluorouracil has become the standard therapy for advanced islet-cell carcinoma. However, doxorubicin has also been shown to be active against this type of tumor, as has chlorozotocin, a drug that is structurally similar to Streptozocin but less frequently causes vomiting. Methods. In this multicenter trial, we randomly assigned 105 patients with advanced islet-cell carcinoma to receive one of three treatment regimens: Streptozocin plus fluorouracil, Streptozocin plus doxorubicin, or chlorozotocin alone. The 31 patients in whom the disease did not respond to treatment were crossed over to chlorozotocin alone or to one of the combination regimens. Results. Streptozocin plus doxorubicin was superior to Streptozocin plus fluorouracil in terms of the rate of tumor regression, measured objectively (69 percent vs. 45 percent, P = 0.05), and the length of time to tumor progression (median, 20 vs. 6.9 months; P = 0.001). Streptozocin plus doxorubicin also ha...
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Streptozocin doxorubicin Streptozocin fluorouracil or chlorozotocin in the treatment of advanced islet cell carcinoma
The New England Journal of Medicine, 1992Co-Authors: Charles G. Moertel, Myrto Lefkopoulo, Stuart R. Lipsitz, Richard G. Hahn, David KlaassenAbstract:Abstract Background. The combination of Streptozocin and fluorouracil has become the standard therapy for advanced islet-cell carcinoma. However, doxorubicin has also been shown to be active against this type of tumor, as has chlorozotocin, a drug that is structurally similar to Streptozocin but less frequently causes vomiting. Methods. In this multicenter trial, we randomly assigned 105 patients with advanced islet-cell carcinoma to receive one of three treatment regimens: Streptozocin plus fluorouracil, Streptozocin plus doxorubicin, or chlorozotocin alone. The 31 patients in whom the disease did not respond to treatment were crossed over to chlorozotocin alone or to one of the combination regimens. Results. Streptozocin plus doxorubicin was superior to Streptozocin plus fluorouracil in terms of the rate of tumor regression, measured objectively (69 percent vs. 45 percent, P = 0.05), and the length of time to tumor progression (median, 20 vs. 6.9 months; P = 0.001). Streptozocin plus doxorubicin also ha...
