CIDeRplusGeneral Information:
| Id: | 4,285 |
| Diseases: |
Diabetes mellitus, type II
- [OMIM]
Insulin resistance Schizophrenia - [OMIM] |
| Mus musculus | |
| female | |
| article | |
| Reference: | Schmidt RH et al.(2013) Olanzapine activates hepatic mammalian target of rapamycin: new mechanistic insight into metabolic dysregulation with atypical antipsychotic drugs J. Pharmacol. Exp. Ther. 347: 126-135 [PMID: 23926289] |
Interaction Information:
| Comment | Olanzapine (OLZ) increased body weight, fat pad mass, and liver-to-body weight ratio without commensurate increase in food consumption, indicating that OLZ altered energy expenditure. |
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Formal Description Interaction-ID: 43973 |
drug/chemical compound increases_activity of phenotype |
| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Olanzapine (OLZ) increased body weight, fat pad mass, and liver-to-body weight ratio without commensurate increase in food consumption, indicating that OLZ altered energy expenditure. |
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Formal Description Interaction-ID: 43974 |
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| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Olanzapine (OLZ) increased body weight, fat pad mass, and liver-to-body weight ratio without commensurate increase in food consumption, indicating that OLZ altered energy expenditure. |
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Formal Description Interaction-ID: 43975 |
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| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Four weeks of olanzapine (OLZ) administration significantly down-regulated the expression of a number of genes involved in lipid biosynthesis, including sterol regulatory element-binding protein 1 (Srebf1), fatty acid synthase (Fasn), and ATP citrate lyase (Acly). Similarly, OLZ exposure upregulated expression of glycogen synthase kinase-3b (Gsk3b), a protein that suppresses glycogen synthesis. These changes in expression of anabolism-regulating genes were accompanied by a significant (2.5-fold) increase in expression of glucokinase (Gck), a key rate-limiting enzyme in glycolysis. Expression of carnitine palmitoyltransferase 1a (Cpt1a), which encodes the rate-limiting enzyme in fatty acid beta-oxidation, was unchanged, as were phosphoenolpyruvate carboxykinase 1 (Pck1; gluconeogenesis) and glucose transporter type 1 and glucose transporter type 4 (Glut1 and Glut4; basal and insulin-mediated glucose transport, respectively). |
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Formal Description Interaction-ID: 43976 |
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| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Four weeks of olanzapine (OLZ) administration significantly down-regulated the expression of a number of genes involved in lipid biosynthesis, including sterol regulatory element-binding protein 1 (Srebf1), fatty acid synthase (Fasn), and ATP citrate lyase (Acly). Similarly, OLZ exposure upregulated expression of glycogen synthase kinase-3b (Gsk3b), a protein that suppresses glycogen synthesis. These changes in expression of anabolism-regulating genes were accompanied by a significant (2.5-fold) increase in expression of glucokinase (Gck), a key rate-limiting enzyme in glycolysis. Expression of carnitine palmitoyltransferase 1a (Cpt1a), which encodes the rate-limiting enzyme in fatty acid beta-oxidation, was unchanged, as were phosphoenolpyruvate carboxykinase 1 (Pck1; gluconeogenesis) and glucose transporter type 1 and glucose transporter type 4 (Glut1 and Glut4; basal and insulin-mediated glucose transport, respectively). |
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Formal Description Interaction-ID: 45990 |
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| Drugbank entries | Show/Hide entries for Olanzapine or FASN |
| Comment | Four weeks of olanzapine (OLZ) administration significantly down-regulated the expression of a number of genes involved in lipid biosynthesis, including sterol regulatory element-binding protein 1 (Srebf1), fatty acid synthase (Fasn), and ATP citrate lyase (Acly). Similarly, OLZ exposure upregulated expression of glycogen synthase kinase-3b (Gsk3b), a protein that suppresses glycogen synthesis. These changes in expression of anabolism-regulating genes were accompanied by a significant (2.5-fold) increase in expression of glucokinase (Gck), a key rate-limiting enzyme in glycolysis. Expression of carnitine palmitoyltransferase 1a (Cpt1a), which encodes the rate-limiting enzyme in fatty acid beta-oxidation, was unchanged, as were phosphoenolpyruvate carboxykinase 1 (Pck1; gluconeogenesis) and glucose transporter type 1 and glucose transporter type 4 (Glut1 and Glut4; basal and insulin-mediated glucose transport, respectively). |
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Formal Description Interaction-ID: 45991 |
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| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Four weeks of olanzapine (OLZ) administration significantly down-regulated the expression of a number of genes involved in lipid biosynthesis, including sterol regulatory element-binding protein 1 (Srebf1), fatty acid synthase (Fasn), and ATP citrate lyase (Acly). Similarly, OLZ exposure upregulated expression of glycogen synthase kinase-3b (Gsk3b), a protein that suppresses glycogen synthesis. These changes in expression of anabolism-regulating genes were accompanied by a significant (2.5-fold) increase in expression of glucokinase (Gck), a key rate-limiting enzyme in glycolysis. Expression of carnitine palmitoyltransferase 1a (Cpt1a), which encodes the rate-limiting enzyme in fatty acid beta-oxidation, was unchanged, as were phosphoenolpyruvate carboxykinase 1 (Pck1; gluconeogenesis) and glucose transporter type 1 and glucose transporter type 4 (Glut1 and Glut4; basal and insulin-mediated glucose transport, respectively). |
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Formal Description Interaction-ID: 45992 |
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| Drugbank entries | Show/Hide entries for Olanzapine or GSK3B |
| Comment | Four weeks of olanzapine (OLZ) administration significantly down-regulated the expression of a number of genes involved in lipid biosynthesis, including sterol regulatory element-binding protein 1 (Srebf1), fatty acid synthase (Fasn), and ATP citrate lyase (Acly). Similarly, OLZ exposure upregulated expression of glycogen synthase kinase-3b (Gsk3b), a protein that suppresses glycogen synthesis. These changes in expression of anabolism-regulating genes were accompanied by a significant (2.5-fold) increase in expression of glucokinase (Gck), a key rate-limiting enzyme in glycolysis. Expression of carnitine palmitoyltransferase 1a (Cpt1a), which encodes the rate-limiting enzyme in fatty acid beta-oxidation, was unchanged, as were phosphoenolpyruvate carboxykinase 1 (Pck1; gluconeogenesis) and glucose transporter type 1 and glucose transporter type 4 (Glut1 and Glut4; basal and insulin-mediated glucose transport, respectively). |
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Formal Description Interaction-ID: 45993 |
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| Drugbank entries | Show/Hide entries for Olanzapine or GCK |
| Comment | Four weeks of olanzapine (OLZ) administration significantly down-regulated the expression of a number of genes involved in lipid biosynthesis, including sterol regulatory element-binding protein 1 (Srebf1), fatty acid synthase (Fasn), and ATP citrate lyase (Acly). Similarly, OLZ exposure upregulated expression of glycogen synthase kinase-3b (Gsk3b), a protein that suppresses glycogen synthesis. These changes in expression of anabolism-regulating genes were accompanied by a significant (2.5-fold) increase in expression of glucokinase (Gck), a key rate-limiting enzyme in glycolysis. Expression of carnitine palmitoyltransferase 1a (Cpt1a), which encodes the rate-limiting enzyme in fatty acid beta-oxidation, was unchanged, as were phosphoenolpyruvate carboxykinase 1 (Pck1; gluconeogenesis) and glucose transporter type 1 and glucose transporter type 4 (Glut1 and Glut4; basal and insulin-mediated glucose transport, respectively). |
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Formal Description Interaction-ID: 45994 |
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| Drugbank entries | Show/Hide entries for Olanzapine or CPT1A |
| Comment | Four weeks of olanzapine (OLZ) administration significantly down-regulated the expression of a number of genes involved in lipid biosynthesis, including sterol regulatory element-binding protein 1 (Srebf1), fatty acid synthase (Fasn), and ATP citrate lyase (Acly). Similarly, OLZ exposure upregulated expression of glycogen synthase kinase-3b (Gsk3b), a protein that suppresses glycogen synthesis. These changes in expression of anabolism-regulating genes were accompanied by a significant (2.5-fold) increase in expression of glucokinase (Gck), a key rate-limiting enzyme in glycolysis. Expression of carnitine palmitoyltransferase 1a (Cpt1a), which encodes the rate-limiting enzyme in fatty acid beta-oxidation, was unchanged, as were phosphoenolpyruvate carboxykinase 1 (Pck1; gluconeogenesis) and glucose transporter type 1 and glucose transporter type 4 (Glut1 and Glut4; basal and insulin-mediated glucose transport, respectively). |
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Formal Description Interaction-ID: 45995 |
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| Drugbank entries | Show/Hide entries for Olanzapine or PCK1 |
| Comment | Four weeks of olanzapine (OLZ) administration significantly down-regulated the expression of a number of genes involved in lipid biosynthesis, including sterol regulatory element-binding protein 1 (Srebf1), fatty acid synthase (Fasn), and ATP citrate lyase (Acly). Similarly, OLZ exposure upregulated expression of glycogen synthase kinase-3b (Gsk3b), a protein that suppresses glycogen synthesis. These changes in expression of anabolism-regulating genes were accompanied by a significant (2.5-fold) increase in expression of glucokinase (Gck), a key rate-limiting enzyme in glycolysis. Expression of carnitine palmitoyltransferase 1a (Cpt1a), which encodes the rate-limiting enzyme in fatty acid beta-oxidation, was unchanged, as were phosphoenolpyruvate carboxykinase 1 (Pck1; gluconeogenesis) and glucose transporter type 1 and glucose transporter type 4 (Glut1 and Glut4; basal and insulin-mediated glucose transport, respectively). |
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Formal Description Interaction-ID: 45996 |
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| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Four weeks of olanzapine (OLZ) administration significantly down-regulated the expression of a number of genes involved in lipid biosynthesis, including sterol regulatory element-binding protein 1 (Srebf1), fatty acid synthase (Fasn), and ATP citrate lyase (Acly). Similarly, OLZ exposure upregulated expression of glycogen synthase kinase-3b (Gsk3b), a protein that suppresses glycogen synthesis. These changes in expression of anabolism-regulating genes were accompanied by a significant (2.5-fold) increase in expression of glucokinase (Gck), a key rate-limiting enzyme in glycolysis. Expression of carnitine palmitoyltransferase 1a (Cpt1a), which encodes the rate-limiting enzyme in fatty acid beta-oxidation, was unchanged, as were phosphoenolpyruvate carboxykinase 1 (Pck1; gluconeogenesis) and glucose transporter type 1 and glucose transporter type 4 (Glut1 and Glut4; basal and insulin-mediated glucose transport, respectively). |
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Formal Description Interaction-ID: 45997 |
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| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Olanzapine (OLZ) increased basal (unfasted) plasma glucose, as indicated by plasma taken at sacrific. |
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Formal Description Interaction-ID: 46100 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | The effect of olanzapine (OLZ) administration on hepatic glycogen storage was assessed by periodic acid-Schiff (PAS) staining. OLZ administration statistically significantly decreased the amount of glycogen stores in unfasted liver by 2-fold compared with control. |
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Formal Description Interaction-ID: 46101 |
drug/chemical compound decreases_activity of process |
| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Amino acids were significantly affected by olanzapine (OLZ): L-glutamine, a putative mediator of mTOR activation, was increased in animals administered OLZ. OLZ also caused a decrease in L-leucine and a parallel increase in L-glutamate, which can act as nitrogen donor and nitrogen acceptor, respectively, in the transamination reaction that regulates the glutamate-glutamine cycle. |
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Formal Description Interaction-ID: 46102 |
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| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Amino acids were significantly affected by olanzapine (OLZ): L-glutamine, a putative mediator of mTOR activation, was increased in animals administered OLZ. OLZ also caused a decrease in L-leucine and a parallel increase in L-glutamate, which can act as nitrogen donor and nitrogen acceptor, respectively, in the transamination reaction that regulates the glutamate-glutamine cycle. |
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Formal Description Interaction-ID: 46103 |
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| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Amino acids were significantly affected by olanzapine (OLZ): L-glutamine, a putative mediator of mTOR activation, was increased in animals administered OLZ. OLZ also caused a decrease in L-leucine and a parallel increase in L-glutamate, which can act as nitrogen donor and nitrogen acceptor, respectively, in the transamination reaction that regulates the glutamate-glutamine cycle. |
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Formal Description Interaction-ID: 46104 |
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| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Given the key role of mTOR in mediating carbohydrate and lipid metabolism and the effects of olanzapine (OLZ) on these pathways, the effect of OLZ administration on the activation of mTOR and dependent signaling cascades was determined by Western blot analysis. OLZ administration increased mTOR activation, as indicated by a statistically significant increase in phosphorylation at Ser248. |
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Formal Description Interaction-ID: 46105 |
drug/chemical compound increases_activity of gene/protein |
| Drugbank entries | Show/Hide entries for Olanzapine or MTOR |
| Comment | Olanzapine (OLZ) treatment also concomitantly increased AMPK activation, as indicated by an increase in phosphorylation at Thr172. |
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Formal Description Interaction-ID: 46106 |
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| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Olanzapine (OLZ) administration caused a complex phenotypic alteration in hepatic carbohydrate metabolism. OLZ administration increased glycolysis without an apparent increase in mitochondrial respiration and favored glycogen depletion. |
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Formal Description Interaction-ID: 46107 |
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| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Olanzapine (OLZ) administration caused a complex phenotypic alteration in hepatic carbohydrate metabolism. OLZ administration increased glycolysis without an apparent increase in mitochondrial respiration and favored glycogen depletion. |
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Formal Description Interaction-ID: 46108 |
drug/chemical compound NOT affects_activity of complex/PPI Mitochondrial respiratory chain |
| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Olanzapine (OLZ) administration caused a slight but significant increase in glucose intolerance and unfasted plasma glucose. |
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Formal Description Interaction-ID: 46109 |
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| Drugbank entries | Show/Hide entries for Olanzapine |
| Comment | Hepatic and plasma triglycerides were elevated by olanzapine (OLZ) administration without a commensurate increase in nonesterified fatty acids (NEFA). |
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Formal Description Interaction-ID: 46110 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Olanzapine |