Abstract: The present invention is directed to substituted pyrazolo[1,5-a]pyridines and related methods for their synthesis and use.

Abstract: The present invention provides pyrazole derivatives represented by the general formula: wherein R1 represents H, an optionally substituted C1-6 alkyl, etc.; one of Q and T represents a group selected from the following: and the other represents -Z-Ar wherein Z represents —O—, —S—, etc.; Ar represents an optionally substituted C6-10 aryl, etc.; R represents an optionally substituted C3-8 cycloalkyl, an optionally substituted C6-10 aryl, etc., pharmaceutically acceptable salts thereof, and prodrugs thereof, which exhibit an excellent inhibitory activity in human sodium/glucose cotransporter (SGLT) and are useful as agents for the prevention, inhibition of progression or treatment of a disease associated with the excess uptake of at least a kind of carbohydrates selected from glucose, fructose and mannose (diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications, etc.

Abstract: The present invention provides pyrazole derivatives represented by the general formula: wherein R1 represents H, an optionally substituted C1-6 alkyl group etc.; one of Q and T represents a group selected from the following groups: and the other represents —(CH2)n—Ar wherein Ar represents an optionally substituted C6-10 aryl group or an optionally substituted C1-9 heteroaryl group; and n represents an integral number from 0 to 2, an optionally substituted C1-6 alkoxyl group, an optionally substituted amino group, an optionally substituted C2-9 heterocycloalkyl group or an optionally substituted heterocycle-fused phenyl group; R represents an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group etc.

Abstract: Pharmaceutical compositions relating to vasoactive intestinal polypeptides and methods for the treatment of metabolic disorders, including diabetes, insulin resistance, metabolic acidosis and obesity are presented. Methods of using the vasoactive intestinal polypeptide compositions are also disclosed.

Abstract: The invention relates to the use of an adsorption material which has been modified with polynuclear metal oxide hydroxides for influencing the calcium level and, in particular, for treating or/and preventing atherosclerotic vascular diseases or/and disturbances of bone metabolism.

Abstract: Activators of peroxisome proliferator-activated receptors comprising a polyprenyl compound, preferably (2E,4E,6E,10E)-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid, as an active ingredient, and medicaments for preventive and/or therapeutic treatment of hyperlipidemia, non-insulin dependent diabetes mellitus or the like comprising a polyprenyl compound as an active ingredient.

Abstract: A process is disclosed for controlling inflammatory tissue access through release of neuropeptides, such as substance P (sP), to insulin-responsive sensory neurons, whereby simultaneous control of insulin sensitivity/resistance is manifested. In models of Type 1 and Type 2 diabetes, sensory afferents, in particular TRPV1, have fundamental roles in insulin/glucose homeostasis, islet physiology and autoimmune tissue inflammation. By manipulation of the TRPV1 neuro-?-cell circuit or enhancement of pancreatic sP levels, normalization of insulin resistance, clearance of inflammation and prevention of both Type 1 and Type 2 diabetes is realized.

Abstract: Method of treating autoimmune conditions are disclosed comprising administering to a mammalian subject IL-12 or an IL-12 antagonist. In certain preferred embodiments the autoimmune condition is one which is promoted by an increase in levels of IFN-? or TNF-?. Suitable conditions for treatment include multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation, Guillain-Barre syndrome, autoimmune thyroiditis, insulin dependent diabetes melitis and autoimmune inflammatory eye disease.

Abstract: A method for preventing or delaying the onset of autoimmune diseases is disclosed.

Abstract: This invention relates to novel compounds that are liver selective glucocorticoid receptor antagonists, to methods of preparing such compounds, and to methods for using such compounds in the regulation of metabolism, especially lowering serum glucose levels, insulin levels, or lipid levels, and/or decreasing body weight.

Abstract: Systemic delivery of insulin to a mammalian host is accomplished by inhalation of a dry powder of insulin. It has been found that dry insulin powders are rapidly absorbed through the alveolar regions of the lungs.

Abstract: Agents useful for the treatment of various metabolic disorders, such as insulin resistance syndrome, diabetes, hyper-lipidemia, fatty liver disease, cachexia, obesity, atherosclerosis and arteriosclerosis are disclosed.

Abstract: A rat model of diabetic nephropathy is disclosed. In another embodiment of the invention, a method of evaluating a test compound's effect of diabetic nephropathy is disclosed. In one embodiment, this method comprises the steps of (a) exposing the test compound to the rat of claim 1, wherein the rat would develop progressive proteinuria and glomerulosclerosis leading to diabetic nephropathy in the absence of the test compound, and (b) comparing the rat's development of diabetic nephropathy with a control T2DN mimic rat that has not been exposed to the test compound.

Abstract: This invention relates to substituted fused heterocyclic C-glycosides, compositions containing them, and methods of using them, for example, for the treatment or prophylaxis of diabetes and Syndrome X.

Abstract: The present invention provides new chemically modified 4-dedimethylaminotetracycline compounds that can be substituted with aryl, alkenyl, or alkynyl groups. The 7, 8, and/or 9 positions and methods for preparing such compounds. Other tetracycline compounds include the 4-dedimethylaminotetracycline derivatives with an oxime group, NH-Alkyl, or N—NH-Alkyl group substituted at the C4 position as well as C2 Mannich derivatives. The present invention also provides a method of treating a mammal suffering from conditions or diseases by administering to the mammal an effective amount of the new chemically modified tetracycline compounds.

Abstract: The subject invention provides compositions and methods for treating diabetes in patients. In a preferred embodiment, the invention provides compositions methods for treating diabetes and/or preventing or alleviating complications associated with diabetes. Specifically exemplified herein is the concurrent administration of a cysteamine compound with at least one additional therapeutic agent to prevent and/or treat diabetes as well as prevent and/or treat complications associated with diabetes. In a preferred embodiment, oral administration of cysteamine hydrochloride with Metformin to a patient diagnosed with diabetes can substantially regulate the patient's glucose metabolism and insulin sensitivity.

Abstract: The use of calcium channel blockers administered intra-nasally to inhibit olfactory sensory perception to treat eating disorders, including obesity, is described. Also described is a method of reducing food intake in a subject by administering a pharmaceutical composition comprising an effective amount of a calcium channel blocker to the nasal mucosa, as well as screening methods for drugs to be used in treating obesity or associated disorders.

Abstract: An hydrogel incorporating a biologically active component is provided that is useful as an interface material for transdermal sensing applications. Specifically, the hydrogel has a crosslinked gel structure and a biologically active component incorporated into the crosslinked gel structure, the biologically active component being capable of converting glucose into a compound having potentiometric activity.

Abstract: The present invention is directed to polypeptides containing at least three amino acids randomly joined in a linear array; wherein at least one of the three amino acids is an aromatic amino acid, at least one of the three amino acids is a charged amino acid and at least one amino acid is an aliphatic amino acid. In a preferred embodiment the polypeptide contains three or four of the following amino acids: tyrosine, alanine, glutamic acid or lysine. According to the present invention, the present polypeptides bind to antigen presenting cells, purified human lymphocyte antigens (HLA) and/or Copolymer 1-specific T cells. Moreover, according to the present invention, these polypeptides can be formulated into pharmaceutical compositions for treating autoimmune disease. The present invention further contemplates methods of treating an autoimmune disease in a mammal by administering a pharmaceutically effective amount of any one of the present polypeptides to the mammal.

Abstract: The present invention relates generally to a method of blunting the postprandial glycemic response to a meal by feeding an acid controlled induced viscosity fiber system. The first component of the induced viscosity fiber system is anionic soluble fiber. The second component of the induced viscosity fiber system is water-insoluble, acid-soluble multivalent cations. The fiber system will typically be incorporated into a meal replacement nutritional. The present invention also refers to a method of delivering soluble fiber to diabetics and to persons needing to lose weight. Additionally, the invention refers to a method of promoting the feeling of fullness and satiety by feeding a nutritional product containing the induced viscosity fiber system.

Abstract: Methods for treating conditions or disorders which can be alleviated by reducing food intake are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist, alone or in conjunction with other compounds or compositions that affect satiety. The methods are useful for treating conditions or disorders, including obesity, Type II diabetes, eating disorders, and insulin-resistance syndrome. The methods are also useful for lowering the plasma glucose level, lowering the plasma lipid level, reducing the cardiac risk, reducing the appetite, and reducing the weight of subjects. Pharmaceutical compositions for use in the methods of the invention are also disclosed.

Abstract: The invention relates inter alia to pharmaceutical compositions containing an extract obtainable from a plant of the genus Trichocaulon or Hoodia having anti-diabetic activity; and to the use of such extracts and to compound (1) as herein defined and its analogues for the manufacture of medicaments having anti-diabetic activity.

Abstract: A pharmaceutical formulation and its use. The pharmaceutical formulation contains peroxidic species or reaction products resulting from oxidation of an alkene, such as geraniol, by an oxygen-containing oxidizing agent, such as ozone; a penetrating solvent, such as dimethylsulfoxide (“DMSO”); a dye containing a chelated metal, such as hematoporphyrin; and an aromatic redox compound, such as benzoquinone. The pharmaceutical formulation is used to effectively treat patients affected with diabetes and obesity.

Abstract: Novel chimeric fusion proteins comprising immunodominant epitopes of GAD and insulin are provided. Also provided are immunomodulatory methods for the use of such proteins for both the prevention and treatment of Type 1 diabetes mellitus. The chimeric fusion proteins of the invention are useful in predicting risk of onset of Type 1 diabetes, determining prognosis of Type 1 diabetes patients early in disease progression, and in evaluating patients for suitability as recipients of transplants of pancreatic cells or tissues. The administration of the proteins of the invention in accordance with the immunomodulatory methods of the invention results in beneficial effects on disease development and severity in patients suffering from or predicted to be at risk of developing Type 1 diabetes, as well as on the outcome of transplants of pancreatic cells or tissues in Type 1 diabetes patients.

Abstract: A method for treating type 1 diabetes in a human in need of such treatment, comprising administering to the human a biologically effective amount of at least one inhibitor of inducible nitric oxide synthase or a pro-inflammatory cytokine, wherein the inhibitor is an inhibitor of HMG-CoA reductase or a pharmaceutically acceptable salt thereof, and the inhibitor specifically inhibits the activity of HMG-CoA reductase.

Abstract: Methods and compositions which are useful in the treatment of amyloidosis. In particular, methods and compositions are provided for inhibiting, preventing and treating amyloid deposition, e.g., in pancreatic islets, wherein the amyloidotic deposits are islet amyloid polypeptide (IAPP)-associated amyloid deposition or deposits. The methods of the invention involve administering to a subject a therapeutic compound which inhibits IAPP-associated amyloid deposits. Accordingly, the compositions and methods of the invention are useful for inhibiting IAPP-associated amyloidosis in disorders in which such amyloid deposition occurs, such as diabetes.

Abstract: A method is provided for treating diabetes and related diseases, especially Type II diabetes, employing an aP2 inhibitor or a combination of an aP2 inhibitor and another antidiabetic agent such as metformin, glyburide, troglitazone and/or insulin.

Abstract: Novel chimeric fusion proteins comprising immunodominant epitopes of GAD and insulin are provided. Also provided are immunomodulatory methods for the use of such proteins for both the prevention and treatment of Type 1 diabetes mellitus. The chimeric fusion proteins of the invention are useful in predicting risk of onset of Type I diabetes, determining prognosis of Type 1 diabetes patients early in disease progression, and in evaluating patients for suitability as recipients of transplants of pancreatic cells or tissues. The administration of the proteins of the invention in accordance with the immunomodulatory methods of the invention results in beneficial effects on disease development and severity in patients suffering from or predicted to be at risk of developing Type 1 diabetes, as well as on the outcome of transplants of pancreatic cells or tissues in Type I diabetes patients.

Abstract: Novel methods, tissues and compositions for increasing the pancreatic mass of a mammalian recipient including harvesting immature pancreatic tissue from a mammalian donor and transplanting said tissue into the peritoneal cavity of a mammalian recipient under conditions that allow the pancreatic tissue to become vascularized and mature, thereby developing a functioning chimeric, endocrine pancreas that produces at least insulin in the recipient. The invention also includes mammalian immature pancreatic tissue adapted for transplantation into the peritoneal cavity of a mammalian recipient for increasing the pancreatic mass of the mammalian recipient as well as methods and compositions for treatment of the pancreatic tissue, recipient immunosuppression and recipient co-stimulatory blockade.

Abstract: Use for the diabetes treatment of compounds or salts thereof, having the following general formula (I): A-(B)b0—(C)c0—NO2 wherein A contains the radical of a drug having an antiinflammatory or analgesic activity, B is a bivalent linking group wherein the precursor must meet the tests described in the application, C is a a bivalent linking group as defined in the invention.

Abstract: A time release composition is provided containing: a chromium complex having formula 3 [Cr3O(carboxylate)6(ligand)3]+??(3) wherein carboxylate is a C2-C5 alkyl carboxylate and wherein ‘ligand’ is a ligand that (i) renders the chromium complex insoluble or only slightly soluble in water and (ii) is acid labile, being readily displaced under acidic conditions below pH=4 and replaced by water to make the resulting water soluble complex 2 [Cr3O(carboxylate)6(H2O)3]+,??(2) and the use of the time release composition for the time release delivery of complex 2.

Abstract: The present invention provides an isolated population of cells containing an expressible nucleic acid encoding proinsulin containing a proinsulin cleavage site and a glucose-regulated expressible nucleic acid encoding a protease capable of cleaving the proinsulin cleavage site to produce insulin. The invention also provides an isolated population of cells which further express a hexosamine synthetic pathway enzyme. The invention additionally provides vectors containing an expressible nucleic acid encoding proinsulin containing a proinsulin cleavage site and a glucose-regulated expressible nucleic acid encoding a protease capable of cleaving the proinsulin cleavage site to produce insulin. The invention further provides a method of treating or preventing diabetes by implanting into an individual cells coexpressing proinsulin containing a proinsulin cleavage site and a glucose-regulated protease capable of cleaving the proinsulin cleavage site to produce insulin.

Abstract: 2-Substituted-5?-O-(1-boranotriphosphate)adenosine derivatives having at position 2 a radical R1 selected from the group consisting of H; halogen; O-hydrocarbyl; S-hydrocarbyl; NR3R4; and hydrocarbyl optionally substituted by halogen, CN, SCN, NO2, OR3, SR3 or NR3R4; wherein R3 and R4 are each independently H or hydrocarbyl or R3 and R4 together with the nitrogen atom to which they are attached form a saturated or unsaturated heterocyclic ring optionally containing 1-2 further heteroatoms selected from oxygen, nitrogen and sulfur, and pharmaceutically acceptable salts or diastereoisomers thereof or a mixture of diastereoisomers, are useful for treatment of type 2 diabetes.

Abstract: The present invention is concerned with a pharmaceutical formulation comprising an amylin agonist and optionally a buffer, a tonicifier or stabilizer, and a preservative in a container, for example, a vial, prefilled cartridge, prefilled syringe or disposable pen. This formulation may be in liquid, gel, solid or powdered form for delivery, for example, via nasal, pulmonary, oral, sublingual, buccal, transdermal, or parenteral routes. Formulation with biocompatible polymers and release modifiers, such as sugars, can facilitate controlled release after injection, minimizing the number of administrations to a patient. These formulations maintain stability upon storage under refrigerated or room temperature conditions. Such formulations can be further combined with insulin for administration to a patient.

Abstract: Carbonyl compounds generated and accumulated in the peritoneal dialysate can be inactivated or eliminated by a carbonyl compound-trapping agent such as aminoguanidine. Carbonyl compounds generated during sterilization and storage of the peritoneal dialysate can be eliminated by pre-contacting with the trapping agent. Further, it is possible to eliminate carbonyl compounds transferred from the blood to the peritoneal cavity of the patient during peritoneal dialysis treatment, by adding the trapping agent to the peritoneal dialysate or by circulating the fluid through a carbonyl compound-trapping cartridge. Intraperitoneal protein modification by carbonyl compounds is inhibited by the present invention, thereby sufficiently reducing peritoneal disorders associated with peritoneal dialysis treatment.

Abstract: The present invention provides glucopyranosyloxypyrazole derivatives represented by the general formula: wherein R1, R2 and R3 represent a hydrogen atom or a halogen atom; R4 represents a lower alkyl group or a halo(lower alkyl) group; and R5 represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, etc., a pharmaceutically acceptable salt thereof or a prodrug thereof., which exert an excellent inhibitory activity in human SGLT2, and therefore are useful as drugs for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, pharmaceutically acceptable salts thereof or prodrugs thereof, production intermediates thereof and pharmaceutical uses thereof.

Abstract: A GLP-1 derivative is provided including an amino acid sequence of GLP-1 (7-35) having deletion, substitution and/or addition of one or more amino acids and having Waa-(Xaa)n-Yaa (in which Waa is Arg or Lys, Xaa is Arg or Lys, n is an integer of 0 to 14, and Yaa is Arg, Arg-NH2, Lys, Lys-NH2 or Hse) added to the C-terminus of the peptide having a GLP-1 activity. These derivatives are highly absorbable via a mucous membrane. The GLP-1 derivative can be conferred with resistance to dipeptidyl peptidase IV by substituting amino acid 8 in its GLP-1 amino acid sequence with Ser, or with resistance to trypsin by substituting amino acids 26 and 34 with Gln and Asn, respectively. The absorption efficiency of the GLP-1 derivatives via mucous membranes can be further improved by preparing a composition using a charge-regulated fat emulsion regulated to be negatively charged thereon.

Abstract: The invention provides a method of treating diabetes in a subject, comprising administering to the diabetic subject an immunotoxin, thereby reducing the subject's T-cell population, and administering to the subject pancreatic islet cells from a donor. The immune tolerance inducing treatment regimen, used optionally with adjunct immunosuppressive agents, prevents pancreatic islet cell rejection while maintaining long term islet cell function following xenogeneic and allogeneic pancreatic islet cell transplantation. Thus, the methods of the present invention provide a means for treating diabetes, wherein the need for exogenous insulin or immunosuppressive agents is decreased or eliminated. Also provided is a method of inhibiting a rejection response of a transplant recipient, comprising administering an immunotoxin during the peritransplant period, thereby transiently reducing the number of T-cell lymphocytes and promoting long-term survival of the transplant.

Abstract: Drug formulations for systemic drug delivery with improved stability and rapid onset of action are described herein. The formulations may be administered via buccal administration, sublingual administration, pulmonary delivery, nasal administration, subcutaneous administration, rectal administration, vaginal administration, or ocular administration. In the preferred embodiments, the formulations are administered sublingually or via subcutaneous injection. The formulations contain an active agent and one or more excipients, selected to increase the rate of dissolution. In the preferred embodiment, the drug is insulin, and the excipients include a metal chelator such as EDTA and an acid such as citric acid. Following administration, these formulations are rapidly absorbed by the oral mucosa when administered sublingually and are rapidly absorbed into the blood stream when administered by subcutaneous injection. In one embodiment, the composition is in the form of a dry powder.

Abstract: The present invention relates to a method of preventing and/or treating diabetes type 2, also, it relates to a method of augmenting Glut4 phosphorylation and Glut4 translocation to a target cell membrane to enhance insulin signal in a signal transduction pathway; further, it relates to a simplified and inexpensive process of obtaining extract and thereafter selectively, its active n-butanol fraction and active molecule Lupinoside PA (LPA4), useful in preventing and/or treating diabetes type 2; and lastly, a pharmaceutical composition thereof.

Abstract: The present invention provides nitrogen-containing heterocyclic derivatives represented by the general formula: wherein X1 and X3 independently represent N or CH; X2 represents N or CR2; X4 represents N or CR3; and with the proviso that one or two of X1, X2, X3 and X4 represent N; R1 represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkoxy-substituted (lower alkyl) group, a lower alkoxy-substituted (lower alkoxy) group, a lower alkoxy(lower alkoxy)-substituted (lower alkyl) group, a cyclic lower alkyl group, a halo(lower alkyl) group or a group represented by the general formula: HO-A- wherein A represents a lower alkylene group, a lower alkyleneoxy group or a lower alkylenethio group; R2 represents a hydrogen atom, a halogen atom, a lower alkyl group, a cyclic lower alkyl group, a lower alkoxy group, an amino group, a (lower acyl)amino group, a mono(lower alkyl)amino group or a di(lower alkyl)amino group; and R3 represents a hydrogen a

Abstract: A method for treating a disease selected from diabetes mellitus and atherosclerosis, and a method for reducing triglycerides and/or increasing HDL cholesterol levels in the plasma of a subject. The method comprises administrating. to a subject an effective amount of crude Dunaliella powder, optionally together with an activator of nuclear receptors.

Abstract: The present invention provides pyrazole-O-glycoside derivatives represented by the following formulae, used as a diabetic medicine

Abstract: The present invention relates to insulin derivatives in which a lipophilic group having from 12 to 40 carbon atoms is attached to the ?-amino group of the N-terminal amino acid in the B-chain or to the carboxy group of the C-terminal amino acid in the B-chain have a protracted profile of action.

Abstract: The invention relates to treatment of patients in need of increasing insulin sensitivity by administration of growth hormone or analogues thereof, preferably human growth hormone, in a low dose and the use of growth hormone or analogues thereof, preferably human growth hormone, for the manufacturing of a medicament useful for increasing insulin sensitivity in low dose therapy. The patient is preferably a normal subject, i.e. not growth hormone deficient patient and/or a non-obese patients. By low dose therapy is preferably meant less than 0.008 mg/kg/day, preferably 0.007 mg/kg/day or less, more preferably 0.005 mg/kg/day or less and most preferably 0.003 mg/kg/day or less. The therapy is preferably performed during short term treatment, preferably less than one month.

Abstract: The present invention relates to novel derivatives of exendin-4 or exendin-4 fragments, wherein the derivatives have a lipophilic substituent attached, optionally via a spacer, to an amino acid residue, which is not the N-terminal or C-terminal amino acid residue of the derivative.

Abstract: A glycoprotein extracted from the fruiting body of Grifola frondosa is demonstrated to have antidiabetic, antihypertensive, antiobesity and antihyperlipidemic effects, and has great potential as an active component for pharmaceuticals, dietary supplements or health food preparations to treat and/or prevent the above diseases. This invention is to provide the glycoprotein and its preparation method.

Abstract: This invention relates the use of glucagon-like peptides such as GLP-1, a GLP-1 analog, or a GLP-1 derivative in methods and compositions for reducing body weight.

Abstract: The present invention relates to the use of NAD(P)H oxidase inhibitors to increase cellular uptake of glucose and in the treatment and/or prevention of diseases caused by insulin resistance or diseases related thereto, such as type II diabetes. Specifically, the invention relates to a method for identifying an agent useful for the treatment or prophylaxis of a medical condition associated with elevated levels of blood glucose, the method comprising (i) contacting a candidate agent with a mammalian NAD(P)H oxidase or NAD(P)H oxidase complex; and (ii) determining whether said candidate agent inhibits the biological activities of the NAD(P)H oxidase or NAD(P)H oxidase complex.

Abstract: Modulation of the activity of the insulin receptor, enhancement of glucose uptake by cells, and other effects significant in the control and management of diabetes are accomplished using compounds of the formula wherein each A is independently a proton-accepting substituent; each R is independently a noninterfering substituent; n is 0, 1, or 2; and each linker is independently an isostere of —NHCONH— or of —N?N— or of —NHCO—. Compounds in the genus of Formula (1) can also be used for structure activity studies to identify features responsible for the relevant activities.