42 results about "Insulin receptor substrate" patented technology

The invention discloses a CRISPR (clustered regularly interspaced short palindromic repeats) / Cas9 system and application thereof to construction of swine-derived recombinant cells with insulin receptor substrate gene defects. The invention provides an sgRNA (ribonucleic acid) combination which is composed of sgRNAIRS1-1, sgRNAIRS1-3, sgRNAIRS2-2 and sgRNAIRS2-3. The invention provides a plasmid combination. The plasmid combination is composed of four plasmids, and the four plasmids are respectively subjected to transcription to obtain sgRNAIRS1-1, sgRNAIRS1-3, sgRNAIRS2-2 and sgRNAIRS2-3. Theapplication of the sgRNA combination or the plasmid combination is as follows: preparation of recombinant cells; preparation of a diabetic cell model; preparation of a diabetic animal model. Accordingto the invention, sgRNAIRS1-1 is as shown in SEQ ID NO:8; sgRNAIRS1-3 is as shown in SEQ ID NO:10; sgRNAIRS2-2 is shown as SEQ ID NO:14; and sgRNAIRS2-3 is as shown in SEQ ID NO:15. A solid foundation is laid for the preparation of diabetic pig models, and important application value for the research and development of diabetic medicaments is achieved.

The invention provides an SgRNA (Small Guide Ribonucleic Acid) targeting sequence of specific target pig IRS1 (Insulin Receptor Substrate 1) gene and application thereof, and relates to the sgRNA targeting sequence and the application. The sgRNA targeting sequence is CGTAGTACTCGAGGCGCGCG. According to the sgRNA targeting sequence provided by the invention, the IRS1 gene can be knocked out or edited through a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) / Cas (CRISPR-associated Protein) 9 system, so that expression of IRS1 can be removed, and the foundation is laid for preparing IRS1 transgenic pigs.

The present invention relates to antisense oligonucleotides that modulate the expression of and / or function of Insulin Receptor Substrate 2 (IRS2) polynucleotides, in particular, by targeting natural antisense polynucleotides of Insulin Receptor Substrate 2 (IRS2) polynucleotides and Transcription factor E3 (TFE3). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of IRS2.

The present invention relates to antisense oligonucleotides that modulate the expression of and / or function of Transcription factor E3 (TFE3) and / or Insulin Receptor Substrate 2 (IRS2) polynucleotides, in particular, by targeting natural antisense polynucleotides of Transcription factor E3 (TFE3) and / or Insulin Receptor Substrate 2 (IRS2). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of TFE3 and / or IRK.

The miRNA miR-33 is shown to inhibit the expression of carnitine O-octaniltransferase (CROT), Carnitine palmitoyltransferase 1A (CPT1a) and hydroxyacyl-CoA-dehydrogenase (HADHB), reduce fatty acid oxidation in hepatic cells, and target the insulin receptor substrate 2 (IRS-2) independent of its ability to elevating plasma high density lipoprotein (HDL) levels. MiR-33 inhibitors are also shown to increase cholesterol efflux from peripheral cells, such as cholesterol-laden macrophages present in atherosclerotic plaques. Compositions and methods are therefore provided for treating or preventing metabolic syndrome and atherosclerosis using miR-33 inhibitors. The miR-33 inhibitors are preferably antagomirs having a single-stranded nucleic acid sequence that is complementary to at least 12 contiguous nucleotides in miR-33 and therefore forms a duplex with miR-33 under physiological conditions.

According to a technical scheme on the first aspect, the invention provides a drug for treatment of polycystic ovary syndrome (PCOS) and abnormal glucose metabolism coexisting diseases. The drug is characterized by including the following four fatty acid components by mass: 17-22% of palmitic acid, 11-23% of hexadecenoic acid, 22-28% of 9-octadecenoic acid, 13-35% of 9, 12, 15-octatecatrienoic acid, and the balance pharmaceutically acceptable additives or excipients. The components are mixed according to compatibility to be prepared into soft capsules and other oral preparations, so that the insulin receptor substrate (IRS) protein level can be effectively reduced so as to inhibit the glucose way, the insulin receptor active time can be increased and the insulin level can be enhanced, and the insulin sensitivity is increased so as to facilitate the reduction of insulin resistance degree. Thus, the drug can have the functions of improving and recuperating ovary ovulatory dysfunction, i.e. PCOS and abnormal glucose metabolism diseases. Compared with other drugs, the drug has simple components, and belongs to highly effective, safety, and simplified drugs.

The present invention relates to a method for promoting expression of insulin receptor substrate-2, comprising administering an effective amount of plasminogen to a subject; furthermore, the present invention relates to a medicament for promoting expression of insulin receptor substrate-2.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more biomarkers selected from the group consisting of Beta-nerve growth factor, Interleukin-17A, Follitropin subunit beta, Collagenase 3, Follistatin, Vitamin D Binding Protein, Islet amyloid polypeptide, Insulin C-peptide, Complement Factor H, Gastric inhibitory polypeptide, Glucagon-like peptide 1, Glucagon, Involucrin, Type II cytoskeletal Keratin-1 / Keratin-10, Type II cytoskeletal Keratin-6A / 6B / 6C, Osteocalcin, Lipopolysaccharide, Pancreatic prohormone, Peptide YY, Agouti-related protein, Ciliary neurotrophic factor, Appetite-regulating hormone, Transthyretin, Insulin receptor substrate 1, and NF-kappa-B inhibitor alpha as diagnostic and prognostic biomarker assays in renal injuries.

Provided is a treatment of cancer using a dual modulator of Insulin Receptor Substrate (IRS) and signal transducer and activator of transcription 3 (Stat3), as well with other agents. The combination can be used to treat a tumor that has developed resistance to an EGFR inhibitor, EGFR antibody, mTOR inhibitor, MEK inhibitor, mutated B-Raf inhibitor, chemotherapeutic agents, and certain combinations thereof, or to prevent acquired resistance of a tumor to any of said inhibitors or agents, or to prevent tumor recurrence following cease of treatment with any of said inhibitors or agents or a combination thereof. The subject matter further provides a treatment of cancer using combination therapy comprising a dual modulator of IRS and Stat3, in combination with an immunotherapy agent. The combination can be used to sensitize a tumor to immunotherapy.

This invention relates to plant extracts containing nutritionally beneficial or medicinally active compounds. Some of these extracts, or the purified compounds contained therein, may be used for the nutritional support, prevention, treatment, or possible cure of various metabolic and other diseases and disorders in human beings and animals, including type 1 and type 2 diabetes, by regulating insulin signaling. This regulatory effect may include modulations of the levels and / or activity of the Insulin Receptor (IR), the Insulin-like Growth Factor (IGF) Receptor, and / or the Insulin Receptor Substrate (IRS) proteins in cells and tissues in the body.

Disclosed are compositions and methods useful in the regulation of cell proliferation. The invention provides TGF-β (transforming growth factor β) and IGFBP-3 (insulin like growth factor binding protein 3) as ligands that engage LRP (low density lipoprotein receptor-related protein), heretofore known as TβR-V (TGF-β receptor V) and IGFBP-3 receptor, to effect a change in the phosphorylation and activation status of IRS (insulin receptor substrate) proteins. Compositions comprising TGF-β or IGFBP-3 and LRP or IRS protein are useful in the inhibition of cell proliferation and in the treatment of various diseases associated with unregulated cell proliferation.

The invention discloses shRNA (short hairpin ribonucleic acid) suppressing IRS1 (insulin receptor substrate 1) gene expression and an application, and belongs to the technical field of gene engineering. A nucleotide sequence of the shRNA is represented by SEQ ID NO.1. The invention further discloses a shRNA interference vector capable of lowering swine-origin IRS1 and IRS2 gene expression simultaneously through connection with a plasmid vector comprising IRS2 genes. Results of swine liver cell IRS gene expression tests indicate that IRS1 genes and the IRS2 genes of swine are lowered by 78% and 64% by the shRNA interference vector respectively. Meanwhile, lowering of the IRS gene expression level affects glucolipid metabolism of swine liver cells, so that the blood sugar concentration of the swine liver cells is increased. According to the shRNA, a foundation is laid for establishment of a type 2 diabetes mellitus swine model, and helpful exploration for increase of the swine blood sugar concentration is conducted.

The invention provides a fructan consisting of 25 beta-D-fructoses and 1 alpha-D-glucose, and a method for preparing the fructan from Hubei dwarf lilyturf tuber serving as a raw material. The fructan has obvious effect of reducing blood sugar of mice with type 2 diabetes, simultaneously improves the sugar tolerance of the mice with the type 2 diabetes, and obviously enhances the expression of insulin receptor (InsR), insulin receptor substrate (IRS-1), protein kinase and phosphatidylinositol3-kinase (PI3-K) to further accelerate the glucose to be converted into glycogen and improve the activities of glucose-6-phosphate and glucose-6-phophatase so as to obvious reduce the insulin resistance.

The miRNA miR-33 is shown to inhibit the expression of carnitine O-octaniltransferase (CROT), Carnitine palmitoyltransferase 1A (CPT1a) and hydroxyacyl-CoA-dehydrogenase (HADHB), reduce fatty acid oxidation in hepatic cells, and target the insulin receptor substrate 2 (IRS-2) independent of its ability to elevating plasma high density lipoprotein (HDL) levels. MiR-33 inhibitors are also shown to increase cholesterol efflux from peripheral cells, such as cholesterol-laden macrophages present in atherosclerotic plaques. Compositions and methods are therefore provided for treating or preventing metabolic syndrome and atherosclerosis using miR-33 inhibitors. The miR-33 inhibitors are preferably antagomirs having a single-stranded nucleic acid sequence that is complementary to at least 12 contiguous nucleotides in miR-33 and therefore forms a duplex with miR-33 under physiological conditions.

This invention relates to plant extracts containing nutritionally beneficial or medicinally active compounds. Some of these extracts, or the purified compounds contained therein, may be used for the nutritional support, prevention, treatment, or possible cure of various metabolic and other diseases and disorders in human beings and animals, including type 1 and type 2 diabetes, by regulating insulin signaling. This regulatory effect may include modulations of the levels and / or activity of the Insulin Receptor (IR), the Insulin-like Growth Factor (IGF) Receptor, and / or the Insulin Receptor Substrate (IRS) proteins in cells and tissues in the body.

Provided is a treatment of cancer using a dual modulator of Insulin Receptor Substrate (IRS) and signal transducer and activator of transcription 3 (Stat3), as well with other agents. The combination can be used to treat a tumor that has developed resistance to an EGFR inhibitor, EGFR antibody, mTOR inhibitor, MEK inhibitor, mutated B-Raf inhibitor, chemotherapeutic agents, and certain combinations thereof, or to prevent acquired resistance of a tumor to any of said inhibitors or agents, or to prevent tumor recurrence following cease of treatment with any of said inhibitors or agents or a combination thereof. The subject matter further provides a treatment of cancer using combination therapy comprising a dual modulator of IRS and Stat3, in combination with an immunotherapy agent. The combination can be used to sensitize a tumor to immunotherapy.

The invention discloses shRNA (short hairpin ribonucleic acid) capable of inhibiting IRS (insulin receptor substrate) 2 gene expression and application thereof, belonging to the technical field of gene engineering. The nucleotide sequence of the shRNA is shown in SEQ ID No.1. The invention also provides an interference vector of shRNA capable of inhibiting IRS 2 gene expression. Through cloning the compared and analyzed pig source IRS 2 gene conserved sequence, interference fragments with restriction enzyme cutting site BamH I and Hind III are synthesized, the interference fragments are connected onto a plasmid vector linearized by BamH I and Hind III, and effective interference vectors are screened out. The shRNA and the interference vector thereof can effectively inhibit IRS2 gene expression, affects cell glucolipid metabolism, and lays a foundation for construction of type 2 diabetic pig model.

The present invention relates to a pharmaceutical composition for preventing or treating diabetes or a complication of diabetes, which includes a TENC1 (tensin like C1 domain-containing phosphatase) expression or activity suppressor, and, more specifically, relates to a pharmaceutical composition for preventing or treating diabetes or a complication of diabetes, which either suppresses the degradation of IRS-1 (insulin receptor substrate-1) or suppresses the phosphorylation of IRS-1 due to the PTPase activity of TENC1. The pharmaceutical composition according to the present invention, which is for preventing or treating diabetes or a complication of diabetes and comprises the TENC1 expression or activity suppressor as an active ingredient, can be expected to be widely usable in preventing and treating diabetes or a complication of diabetes since the pharmaceutical composition can effectively prevent the muscular dystrophy and reduction in sugar adsorption that occur due to reduction in IRS-1 by suppressing degradation of IRS-1 caused by TENC1.

The invention discloses a use of a long non-coding ribonucleic acid NONRATT021972 small interfering RNA in preparation of a drug for treating diabetes mellitus with cardiac autonomic nervous system diseases. An experiment observation result shows that the long non-coding ribonucleic acid NONRATT021972 small interfering RNA can improve diabetic model rat cardiac function anomalous change, reduce risen blood sugar, a serum inflammatory factor level and an oxidative stress level, and improve antioxidation substance activity. Through long non-coding ribonucleic acid NONRATT021972 small interfering RNA-based treatment, up-regulated expression of diabetic model rat superior cervical ganglia gap junction hemichannel protein 1 (Pannexin-1) is substantially inhibited, insulin receptor substrate-1 (IRS-1) abnormal serine 302 phosphorylation is inhibited and down-regulated IRS-1 expression is improved. The NONRATT021972 small interfering RNA can be used in Pannexin-1 and IRS-1 dysfunction mediated disease treatment drugs. The long non-coding ribonucleic acid NONRATT021972 small interfering RNA in forms of an oral medicine, an injection, a lozenge or other local or whole body agents can prevent and treat the above diseases.

The present invention relates to the treatment of cancer using combination therapy comprising a dual modulator of Insulin Receptor Substrate (IRS) and signal transducer and activator of transcription3 (Stat3), in combination with an antibody against programmed cell death 1 (PD-1) protein, an anti-programmed cell death protein 1 ligand (PD-L1) antibody, or a combination thereof. The combination can be used to re-sensitize a tumor that may develop or has developed resistance to the anti-PD-1 and / or anti-PD-L1 antibody, by enhancing response of the tumor to the anti-PD-1 and / or anti-PD-L1 antibody, converting non- responding tumors to responders and / or blocking tumor progression.

The present invention relates to a pharmaceutical composition for preventing or treating diabetes or a complication of diabetes, which includes a TENC1 (tensin like C1 domain-containing phosphatase) expression or activity suppressor, and, more specifically, relates to a pharmaceutical composition for preventing or treating diabetes or a complication of diabetes, which either suppresses the degradation of IRS-1 (insulin receptor substrate-1) or suppresses the phosphorylation of IRS-1 due to the PTPase activity of TENC1. The pharmaceutical composition according to the present invention, which is for preventing or treating diabetes or a complication of diabetes and comprises the TENC1 expression or activity suppressor as an active ingredient, can be expected to be widely usable in preventing and treating diabetes or a complication of diabetes since the pharmaceutical composition can effectively prevent the muscular dystrophy and reduction in sugar adsorption that occur due to reduction in IRS-1 by suppressing degradation of IRS-1 caused by TENC1.

A pharmaceutical composition for preventing and treating endocrine disrupting chemicals-induced diseases and a treating method using the same. Since the composition has an effect of decreasing lipid accumulation caused by endocrine disrupting chemicals, for example, persistent organic pollutants (POPs) including polychlorinated biphenyl and the like and can improve insulin resistance caused by the POPs through reduction of insulin receptor substrate 1 (IR1), the composition can be helpfully used for treating diseases including obesity, insulin resistance, and the like caused by the endocrine disrupting chemicals. Further, according to the present disclosure, the composition has an effect of excreting the endocrine disrupting chemicals.

The research is different from other previous researches, and the action mechanism of the astragalus flavone extract for treating the type 2 diabetes mellitus is discussed by applying a biological method. Skeletal muscle cells are taken as experimental subjects, an experimental group for blocking a P13 / Akt signal channel is constructed, then the astragalus flavone extract is given, liver cell related carbohydrate gene expression is analyzed, and the cellular mechanism of the astragalus flavone extract for treating type 2 diabetes mellitus is discussed. At present, the research is not reported at home and abroad. Therefore, a novel treatment method is provided by the astragalus flavone extract. By using the method, lots of expenditures for purchasing db / db mice and double-gene knockout mice can be saved. According to the research, the protein expression level of an insulin receptor substrate P-IRS-1 is measured, then the influence of the astragalus flavone extract on the insulin sensitivity of mouse myoblasts (C2C12) is detected, and a theoretical basis is provided for treatment of type 2 diabetes mellitus.

The invention discloses newly-discovered phosphorylation sites in human IRS-1 and IRS-2, serine 1101 (Ser1101) and serine 1149 (Ser1149) respectively, and provides antibodies, both polyclonal and monoclonal, that selectively bind to IRS-1 and / or IRS-2 when phosphorylated at these respective sites, but do not bind to IRS-1 and / or IRS-2 when not phosphorylated at these respective sites. The sites are relevant to insulin-resistance in type 2 diabetes. Also provided are methods for determining the phosphorylation of IRS-1 / 2 or activity of PKC theta in a biological sample, by using a detectable reagent, such as the disclosed antibodies, that binds to IRS-1 / 2 only when phosphorylated at Ser1101 / Ser1149. Kits comprising the phosphor-IRS-1 / 2 (Ser1101 / 1149) antibodies of the invention are also provided.

The invention provides a fructan consisting of 25 beta-D-fructoses and 1 alpha-D-glucose, and a method for preparing the fructan from Hubei dwarf lilyturf tuber serving as a raw material. The fructan has obvious effect of reducing blood sugar of mice with type 2 diabetes, simultaneously improves the sugar tolerance of the mice with the type 2 diabetes, and obviously enhances the expression of insulin receptor (InsR), insulin receptor substrate (IRS-1), protein kinase and phosphatidylinositol3-kinase (PI3-K) to further accelerate the glucose to be converted into glycogen and improve the activities of glucose-6-phosphate and glucose-6-phophatase so as to obvious reduce the insulin resistance.