Drug Information
Drug (ID: DG00461) and It's Reported Resistant Information
Name |
Insulin
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Synonyms |
BrioDurance; Insulin (agglomerated vesicle technology, diabetes), Cense Biosciences; Insulin (subcutaneous/nanoparticle/suspension/sustained release formulation, diabetes); Insulin (subcutaneous/nanoparticle/suspension/sustained release formulation, diabetes), Cense Biosciences
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Indication |
In total 1 Indication(s)
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Drug Resistance Disease(s) |
Disease(s) with Clinically Reported Resistance for This Drug
(3 diseases)
COVID-19 [ICD-11: 1D92]
[2]
Nonalcoholic fatty liver disease [ICD-11: DB92]
[3]
Type 2 diabetes mellitus [ICD-11: 5A11]
[4]
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Click to Show/Hide the Molecular Information and External Link(s) of This Drug | |||||
TTD Drug ID | |||||
DrugBank ID |
Type(s) of Resistant Mechanism of This Drug
UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-05: Endocrine/nutritional/metabolic diseases
Type 2 diabetes mellitus [ICD-11: 5A11]
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Key Molecule: CREB/ATF bZIP transcription factor (CREBZF) | [4] | |||
Molecule Alteration | Expression | Down-regulation |
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Resistant Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Adipocyte-specific basic region-leucine zipper (B-ZIP) transcription factor knockout mice, which are called A-ZIP/F-1 fatless mice due to a lack of white fat tissue, are hyperinsulinemic and hyperglycemic, due to severe defects in IRS-1 and -2 associated PI3K activity in muscle and liver. The overexpression of preadipocyte factor-1 (Pref-1), a secreted protein that inhibits adipocyte differentiation, also induced the characteristics of lipodystrophic models, that is, reduced adipose tissue mass, dyslipidemia, and insulin resistance. In addition, the inhibition of de novo sphingolipid biosynthesis by adipocyte-specific knockout of serine palmitoyltransferase 2 (Sptlc2), which catalyzes the first step of de novo sphingolipid synthesis, exhibited impaired adipose tissue development and a lipodystrophic phenotype, which progressed to systemic insulin resistance. The ability to form unilocular lipid droplets in white adipocytes is required to maintain the ability of white adipocytes to store lipids. Knock out mice of fat-specific protein 27 (Fsp27) showed multilocular lipid droplets in adipocytes and increased lipolysis, resulting in hepatic steatosis and insulin resistance. | |||
Key Molecule: Cell death activator CIDE-3 (CIDEC) | [4] | |||
Molecule Alteration | Expression | Down-regulation |
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Resistant Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Adipocyte-specific basic region-leucine zipper (B-ZIP) transcription factor knockout mice, which are called A-ZIP/F-1 fatless mice due to a lack of white fat tissue, are hyperinsulinemic and hyperglycemic, due to severe defects in IRS-1 and -2 associated PI3K activity in muscle and liver. The overexpression of preadipocyte factor-1 (Pref-1), a secreted protein that inhibits adipocyte differentiation, also induced the characteristics of lipodystrophic models, that is, reduced adipose tissue mass, dyslipidemia, and insulin resistance. In addition, the inhibition of de novo sphingolipid biosynthesis by adipocyte-specific knockout of serine palmitoyltransferase 2 (Sptlc2), which catalyzes the first step of de novo sphingolipid synthesis, exhibited impaired adipose tissue development and a lipodystrophic phenotype, which progressed to systemic insulin resistance. The ability to form unilocular lipid droplets in white adipocytes is required to maintain the ability of white adipocytes to store lipids. Knock out mice of fat-specific protein 27 (Fsp27) showed multilocular lipid droplets in adipocytes and increased lipolysis, resulting in hepatic steatosis and insulin resistance. | |||
Key Molecule: Preadipocyte factor (PREF-1) | [4] | |||
Molecule Alteration | Expression | Up-regulation |
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Resistant Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Adipocyte-specific basic region-leucine zipper (B-ZIP) transcription factor knockout mice, which are called A-ZIP/F-1 fatless mice due to a lack of white fat tissue, are hyperinsulinemic and hyperglycemic, due to severe defects in IRS-1 and -2 associated PI3K activity in muscle and liver. The overexpression of preadipocyte factor-1 (Pref-1), a secreted protein that inhibits adipocyte differentiation, also induced the characteristics of lipodystrophic models, that is, reduced adipose tissue mass, dyslipidemia, and insulin resistance. In addition, the inhibition of de novo sphingolipid biosynthesis by adipocyte-specific knockout of serine palmitoyltransferase 2 (Sptlc2), which catalyzes the first step of de novo sphingolipid synthesis, exhibited impaired adipose tissue development and a lipodystrophic phenotype, which progressed to systemic insulin resistance. The ability to form unilocular lipid droplets in white adipocytes is required to maintain the ability of white adipocytes to store lipids. Knock out mice of fat-specific protein 27 (Fsp27) showed multilocular lipid droplets in adipocytes and increased lipolysis, resulting in hepatic steatosis and insulin resistance. | |||
Key Molecule: Serine palmitoyltransferase long chain base subunit 2 (SPTLC2) | [4] | |||
Molecule Alteration | Expression | Down-regulation |
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Resistant Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Adipocyte-specific basic region-leucine zipper (B-ZIP) transcription factor knockout mice, which are called A-ZIP/F-1 fatless mice due to a lack of white fat tissue, are hyperinsulinemic and hyperglycemic, due to severe defects in IRS-1 and -2 associated PI3K activity in muscle and liver. The overexpression of preadipocyte factor-1 (Pref-1), a secreted protein that inhibits adipocyte differentiation, also induced the characteristics of lipodystrophic models, that is, reduced adipose tissue mass, dyslipidemia, and insulin resistance. In addition, the inhibition of de novo sphingolipid biosynthesis by adipocyte-specific knockout of serine palmitoyltransferase 2 (Sptlc2), which catalyzes the first step of de novo sphingolipid synthesis, exhibited impaired adipose tissue development and a lipodystrophic phenotype, which progressed to systemic insulin resistance. The ability to form unilocular lipid droplets in white adipocytes is required to maintain the ability of white adipocytes to store lipids. Knock out mice of fat-specific protein 27 (Fsp27) showed multilocular lipid droplets in adipocytes and increased lipolysis, resulting in hepatic steatosis and insulin resistance. | |||
Key Molecule: Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1) | [4] | |||
Molecule Alteration | Expression | Up-regulation |
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Resistant Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Marshall et al. first suggested O-GlcNAcylation modulated insulin sensitivity and showed that the effects of glucose-induced insulin resistance could be blocked by inhibiting GFAT using amidotransferase inhibitors such as O-diazoacetyl-L-serine (azaserine) or 6-diazo-5-oxonorleucine (DON). Subsequently, it was established that glucosamine induces insulin resistance. | |||
Key Molecule: Serine palmitoyltransferase small subunit B (SPTSB) | [4] | |||
Molecule Alteration | Expression | Up-regulation |
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Resistant Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Obese rats with insulin resistance have consistently been reported to exhibit elevated hepatic and muscle ceramide contents. Inhibition of ceramide synthesis using myriocin, an inhibitor of serine palmitoyltransferase, prevented insulin resistance and attenuated ceramide contents in fat-fed mice. | |||
Key Molecule: O-GlcNAcase (OGA) | [4] | |||
Molecule Alteration | Expression | Up-regulation |
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Resistant Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Recently, skeletal muscle-specific O-GlcNAc transferase (OGT) knockout mice on a HFD were reported to have low plasma glucose levels and glucose tolerances. Moreover, the overexpression of O-GlcNAcase (OGA), which removes O-GlcNAc from proteins, significantly improved whole-body glucose tolerance and insulin sensitivity in db/db mice, and O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) (an OGA inhibitor) suppressed insulin-mediated glucose uptake in adipocytes. | |||
Key Molecule: O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) | [4] | |||
Molecule Alteration | Expression | Up-regulation |
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Resistant Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Recently, skeletal muscle-specific O-GlcNAc transferase (OGT) knockout mice on a HFD were reported to have low plasma glucose levels and glucose tolerances. Moreover, the overexpression of O-GlcNAcase (OGA), which removes O-GlcNAc from proteins, significantly improved whole-body glucose tolerance and insulin sensitivity in db/db mice, and O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) (an OGA inhibitor) suppressed insulin-mediated glucose uptake in adipocytes. | |||
Key Molecule: Lipoprotein lipase (LPL) | [4] | |||
Molecule Alteration | Expression | Up-regulation |
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Resistant Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Several studies have shown that lipid accumulation in liver and skeletal muscle caused by short-term HFD feeding or lipid/heparin infusions induce insulin resistance in rats. In addition, overexpression of lipoprotein lipase (LPL) in liver or muscle induced peripheral insulin resistance and the accumulation of lipid in respective tissues, and skeletal muscle-specific LPL deletion enhanced insulin signaling in HFD challenged muscle. Furthermore, deleting fat transport proteins such as CD36 or FATP-1 increased insulin-mediated glucose uptake in skeletal muscle, and liver-specific knockdown of FATP2 or FATP5 significantly reduced HFD-induced hepatosteatosis and increased glucose tolerance. | |||
Key Molecule: Protein kinase C theta (PRKCT) | [4] | |||
Molecule Alteration | Expression | Up-regulation |
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Resistant Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | The DAG hypothesis of lipid-induced insulin resistance is that interference of insulin signaling by activated protein kinase C (PKC) results from the accumulation of DAG within insulin-sensitive tissues. In a manner similar to that observed in liver, the accumulation of intramyocellular DAG impairs insulin signaling and muscle glucose uptake by activating PKCtheta (muscle-type nPKC), which elicits the phosphorylation of IRS-1 at Ser1101 and blocks the insulin-stimulated phosphorylation of IRS-1. Large-scale studies have also corroborated the DAG-PKC induced hypothesis of insulin resistance. |
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Key Molecule: Ceramide synthase 6 (CERS6) | [4] | |||
Molecule Alteration | Expression | Down-regulation |
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Sensitive Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Also, liver-specific knock out of ceramide synthase 6 (CerS6) decreased hepatic ceramide levels (especially C16:0 species), protected against HFD-induced obesity, and improved glucose tolerance. | |||
Key Molecule: Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1) | [4] | |||
Molecule Alteration | Expression | Down-regulation |
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Sensitive Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Marshall et al. first suggested O-GlcNAcylation modulated insulin sensitivity and showed that the effects of glucose-induced insulin resistance could be blocked by inhibiting GFAT using amidotransferase inhibitors such as O-diazoacetyl-L-serine (azaserine) or 6-diazo-5-oxonorleucine (DON). Subsequently, it was established that glucosamine induces insulin resistance. | |||
Key Molecule: Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1) | [4] | |||
Molecule Alteration | Expression | Down-regulation |
||
Sensitive Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Marshall et al. first suggested O-GlcNAcylation modulated insulin sensitivity and showed that the effects of glucose-induced insulin resistance could be blocked by inhibiting GFAT using amidotransferase inhibitors such as O-diazoacetyl-L-serine (azaserine) or 6-diazo-5-oxonorleucine (DON). Subsequently, it was established that glucosamine induces insulin resistance. | |||
Key Molecule: Serine palmitoyltransferase small subunit B (SPTSB) | [4] | |||
Molecule Alteration | Expression | Down-regulation |
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Sensitive Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Obese rats with insulin resistance have consistently been reported to exhibit elevated hepatic and muscle ceramide contents. Inhibition of ceramide synthesis using myriocin, an inhibitor of serine palmitoyltransferase, prevented insulin resistance and attenuated ceramide contents in fat-fed mice. | |||
Key Molecule: O-GlcNAcase (OGA) | [4] | |||
Molecule Alteration | Expression | Down-regulation |
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Sensitive Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Recently, skeletal muscle-specific O-GlcNAc transferase (OGT) knockout mice on a HFD were reported to have low plasma glucose levels and glucose tolerances. Moreover, the overexpression of O-GlcNAcase (OGA), which removes O-GlcNAc from proteins, significantly improved whole-body glucose tolerance and insulin sensitivity in db/db mice, and O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) (an OGA inhibitor) suppressed insulin-mediated glucose uptake in adipocytes. | |||
Key Molecule: O-GlcNAcase (OGA) | [4] | |||
Molecule Alteration | Expression | Down-regulation |
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Sensitive Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Recently, skeletal muscle-specific O-GlcNAc transferase (OGT) knockout mice on a HFD were reported to have low plasma glucose levels and glucose tolerances. Moreover, the overexpression of O-GlcNAcase (OGA), which removes O-GlcNAc from proteins, significantly improved whole-body glucose tolerance and insulin sensitivity in db/db mice, and O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc) (an OGA inhibitor) suppressed insulin-mediated glucose uptake in adipocytes. | |||
Key Molecule: CD36 molecule (CD36) | [4] | |||
Molecule Alteration | Expression | Down-regulation |
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Sensitive Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Several studies have shown that lipid accumulation in liver and skeletal muscle caused by short-term HFD feeding or lipid/heparin infusions induce insulin resistance in rats. In addition, overexpression of lipoprotein lipase (LPL) in liver or muscle induced peripheral insulin resistance and the accumulation of lipid in respective tissues, and skeletal muscle-specific LPL deletion enhanced insulin signaling in HFD challenged muscle. Furthermore, deleting fat transport proteins such as CD36 or FATP-1 increased insulin-mediated glucose uptake in skeletal muscle, and liver-specific knockdown of FATP2 or FATP5 significantly reduced HFD-induced hepatosteatosis and increased glucose tolerance. | |||
Key Molecule: Long-chain fatty acid transport protein 1 (S27A1) | [4] | |||
Molecule Alteration | Expression | Down-regulation |
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Sensitive Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Several studies have shown that lipid accumulation in liver and skeletal muscle caused by short-term HFD feeding or lipid/heparin infusions induce insulin resistance in rats. In addition, overexpression of lipoprotein lipase (LPL) in liver or muscle induced peripheral insulin resistance and the accumulation of lipid in respective tissues, and skeletal muscle-specific LPL deletion enhanced insulin signaling in HFD challenged muscle. Furthermore, deleting fat transport proteins such as CD36 or FATP-1 increased insulin-mediated glucose uptake in skeletal muscle, and liver-specific knockdown of FATP2 or FATP5 significantly reduced HFD-induced hepatosteatosis and increased glucose tolerance. | |||
Key Molecule: Very long-chain acyl-CoA synthetase (S27A2) | [4] | |||
Molecule Alteration | Expression | Down-regulation |
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Sensitive Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Several studies have shown that lipid accumulation in liver and skeletal muscle caused by short-term HFD feeding or lipid/heparin infusions induce insulin resistance in rats. In addition, overexpression of lipoprotein lipase (LPL) in liver or muscle induced peripheral insulin resistance and the accumulation of lipid in respective tissues, and skeletal muscle-specific LPL deletion enhanced insulin signaling in HFD challenged muscle. Furthermore, deleting fat transport proteins such as CD36 or FATP-1 increased insulin-mediated glucose uptake in skeletal muscle, and liver-specific knockdown of FATP2 or FATP5 significantly reduced HFD-induced hepatosteatosis and increased glucose tolerance. | |||
Key Molecule: Bile acyl-CoA synthetase (S27A5) | [4] | |||
Molecule Alteration | Expression | Down-regulation |
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Sensitive Disease | Type 2 diabetes mellitus [ICD-11: 5A11.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Several studies have shown that lipid accumulation in liver and skeletal muscle caused by short-term HFD feeding or lipid/heparin infusions induce insulin resistance in rats. In addition, overexpression of lipoprotein lipase (LPL) in liver or muscle induced peripheral insulin resistance and the accumulation of lipid in respective tissues, and skeletal muscle-specific LPL deletion enhanced insulin signaling in HFD challenged muscle. Furthermore, deleting fat transport proteins such as CD36 or FATP-1 increased insulin-mediated glucose uptake in skeletal muscle, and liver-specific knockdown of FATP2 or FATP5 significantly reduced HFD-induced hepatosteatosis and increased glucose tolerance. |
ICD-09: Visual system diseases
Retinopathy [ICD-11: 9B71]
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Key Molecule: Parkinson disease protein 7 homolog (PARK7) | [1] | |||
Molecule Alteration | Expression | Up-regulation |
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Sensitive Disease | Diabetic retinopathy [ICD-11: 9B71.0] | |||
Experimental Note | Revealed Based on the Cell Line Data | |||
Cell Pathway Regulation | Cell apoptosis | Inhibition | hsa04210 | |
Nrf2 signaling pathway | Inhibition | hsa05208 | ||
Experiment for Molecule Alteration |
Western blotting analysis | |||
Experiment for Drug Resistance |
TUNEL staining assay | |||
Mechanism Description | After DJ-1 overexpression, apoptosis of rat retinal pericytes (RRPs) decreased, the ratio of B-cell lymphoma-2 (Bcl-2) to BCL2-Associated X Protein (BAX) increased, the production of ROS decreased, and the protein expression and activity of manganese superoxide dismutase (MnSOD, also called SOD2) and catalase (CAT) increased. DJ-1 overexpression activated Nrf2 expression, however, after Nrf2 silencing, apoptosis of RRPs increased, the ratio of Bcl-2 to BAX decreased, the production of ROS increased, the protein expression of MnSOD and CAT decreased, and the expression of heme oxygenase-1 (HO-1), NADP(H) quinone oxidoreductase (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC) and modifier subunit (GCLM) decreased. |
References
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