Abstract: Conjugates of a polymer having attached thereto an angiogenesis targeting moiety and a therapeutically active agent such as an anti-cancer agent or anti-angiogenesis agent, and processes of preparing same are disclosed. Pharmaceutical compositions containing these conjugates and uses thereof in the treatment of angiogenesis-related medical conditions such as cancer and cancer metastases are also disclosed.

Abstract: The present invention provides a compound of Formula (I) a pharmaceutically salt thereof wherein R1, R2, Ra, L, Z, Z1 and Z2 are as defined herein, that act as Ghrelin antagonists or inverse agonists; pharmaceutical compositions thereof; and methods of treating diseases, disorders, or conditions mediated by the antagonism of the Ghrelin receptor.

Abstract: One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention.

Abstract: The invention is directed to a fusion protein comprising at least one FGF-21 (fibroblast growth factor-21) compound and at least one GLP-1R (glucagon-like peptide-1 receptor) agonist as well as to pharmaceutical compositions, medical uses and methods of treatment involving the fusion protein, particularly in the field of diabetes, dyslipidemia, obesity and/or adipositas.

Abstract: The present invention provides peptides and pharmaceutical compositions thereof for appetite suppression and weight control. Preferred peptides are calcitonin analogs, preferably with specific amino acid changes to make the peptide more amylin-like.

Abstract: The present invention relates to an activin receptor type II B (ACVR2B) inhibitor which comprises the delta-like 1 homolog (DLK1) extracellular water-soluble domain. More specifically, the present invention relates to an extracellular soluble domain of DLK1; fragments of the extracellular soluble domain of DLK1; mutants of the extracellular soluble domain of DLK1; a composition for suppressing ligand linkage with the ACVR2B receptor, which includes a fragment of the mutants as an active ingredient; and a pharmaceutical composition for prevention and treatment of diseases which comprises the same. The composition of the present invention competitively binds to the ACVR2B receptor and inhibits the binding of an ACVR2B ligand to the ACVR2B receptor, which inhibits protein signalling associated with such ligands, and will be useful for prevention and treatment of diseases associated therewith.

Abstract: CXCR4 and ROBO-1 are biomarkers associated with type 1 diabetes. Expression of CXCR4 and ROBO-1 in peripheral CD3 T cells is substantially higher in patients with autoimmune diabetes (type 1 diabetes) than in non-diabetic patients. Therapies are disclosed for reducing the progression of type 1 diabetes, and to reduce the risk of developing type 1 diabetes in patients who are at risk of developing type 1 diabetes.

Abstract: The present invention relates to novel polymer conjugates of polypeptide variants of the HMGB1 high affinity binding domain Box-A (HMGB1 Box-A) or of a biologically active fragment of HMGB1 Box-A. Further, the invention relates to novel polymer conjugates of polypeptide variants of the HMGB1 high affinity binding domain Box-A (HMGB1 Box-A). Moreover, the present invention concerns the use of said polymer conjugates of polypeptide molecules of HMGB1 Box-A to diagnose, prevent, alleviate and/or treat pathologies associated with extracellular HMGB1 and/or associated with an increased expression of RAGE.

Abstract: Methods are provided of treating or preventing diabetes in a subject comprising administering to the subject an amount of oxytocin or an oxytocin analog. Methods are also provided of increasing insulin secretion in a subject comprising administering to the subject an amount of oxytocin or an oxytocin analog.

Abstract: This document provides methods and material related to natriuretic polypeptides. For example, substantially pure polypeptides having a natriuretic peptide activity, nucleic acids encoding polypeptides having a natriuretic peptide activity, host cells containing such nucleic acids, and methods for inducing a natriuretic or diuretic activity within a mammal are provided.

Abstract: ZSCAN4, a gene expressed in ES cells and 2-cell stage embryos, has been previously shown to regulate telomere elongation and genome stability in mouse ES cells. It is disclosed herein that in the adult human pancreas, a small number of ZSCAN4-positive cells are present among cells located in the islets of Langerhans, acini, and ducts. These data disclosed herein indicates that expression of ZSCAN4 is a marker for rare stem/progenitor cells in adult human pancreas. Thus, provided herein is a method of isolating pancreatic stem cells or progenitor cell from a sample by detecting expression of ZSCAN4. Also provided is a method of treating diabetes by isolating ZSCAN4+ pancreatic stem cells or progenitor cells, expanding the cells in vitro and transplanted the expanded cells into the subject. The expanded ZSCAN4+ cells can optionally be differentiated into pancreatic ? cells before transplanting the cells into the subject.

Abstract: The present invention is directed to peptide compositions and methods of using the peptide compositions to treat prediabetes, diabetes, obesity, high blood pressure and metabolic syndrome.

Abstract: In order to provide a composition for treating, improving, or preventing pain, it has been found out that a metallothionein protein is expressed in a normal peripheral nerve, and that the expression is not observed in a peripheral nerve producing pain. Moreover, it has been found out that administering metallothionein to rats having neuropathic pain suppresses the pain in the rats.

Abstract: Diseases including diabetes, metabolic syndrome, and obesity or obesity-related diseases are due to impairment in glucose metabolism. The skeleton has been shown to regulate energy metabolism and play a role in glucose metabolism. The present invention relates to methods for treating or preventing diseases such as diabetes, metabolic syndrome, and obesity or obesity-related by administering a therapeutically effective amount of osteoblast-expressed Lcn-2 or a biologically active fragment.

Abstract: The present invention describes the use of translation inhibitors for the treatment of cancer and other disorders. Described herein are translation-inhibiting compounds, and methods of using those compounds for the treatment of cancer and other disorders. In some aspects the compounds inhibit translation elongation at the ribosome. In some aspects the compounds are used alone or in combination with known therapies.

Abstract: This invention relates to a plurality of compositions for dietary health management and its use in the prevention or treatment of any one of the disease states in the group consisting of cardiovascular disease, inflammation and diarrhoea. Human evolution has been a very slow process in contrast to the relatively recent, rapid changes in our diet since the Neolithic revolution which marked the switch from hunter-gatherer to agricultural life-style around 10,000 years ago. Moreover our genome has not had time to evolve at the same pace and therefore it is postulated that our bodies will work more efficiently with an ancestral diet.

Abstract: The present invention provides methods for increasing arterial compliance. The methods generally involve administering to an individual in need thereof an effective amount of relaxin. The present invention further provides methods of increasing arterial compliance in individuals who have Type 1 or Type 2 diabetes. The present invention further provides methods of increasing arterial compliance in perimenopausal, menopausal, and post-menopausal women. The present invention further provides methods of increasing arterial compliance in individuals who have or who are at risk of developing age-associated arterial stiffness.

Abstract: Increased in vivo and/or in vitro stability is imparted to a biologically active protein by fusing to an amino acid sequence consisting of at least about 100 amino acid residues, which consist essentially of Alanine, Serine and Proline, which form a random coil conformation. Specific examples are described. Also described are related nucleic acids, vectors and cells encoding such amino acids; compositions of biologically active proteins fused to a random coil domain, and methods of making and using the compounds and compositions of the invention.

Abstract: A method for regenerating pancreatic tissue using recombinant periostin protein, a nucleic acid encoding said periostin and pharmaceutical compositions comprising said periostin are disclosed. Isolation of a nucleic acid encoding a periostin isoform, panc, is also taught.

Abstract: Methods for prevention and treatment of type-2 diabetes comprising administering to the subject an effective amount of FTY-720 or an analog are described.

Abstract: The present invention is based on the discovery that Humanin and humanin analogues protect pancreatic beta cells in vitro and in vivo from apoptosis. Accordingly, humanin and its analogues are useful for preventing and treating diabetes and promoting beta cell survival in a number of applications.

Abstract: Provided herein are four polypeptides, named PRT5, PRT6, PRT7 and PRT8, the nucleic acids encoding the same, compositions comprising the proteins, as well as their uses in therapeutic and diagnostic methods. Antibodies which specifically recognize the polypeptides are also provided, as well as their uses. Characterization of each protein showed that PRT5 and PRT8 are involved in glucose metabolism, PRT6 is involved in androgen regulation, while PRT7 correlates with cancer.

Abstract: The invention relates to a pharmaceutical composition comprising 1.a and/or 1.b according to claim 1 in combination with at least one second therapeutic agent 2 which is suitable in the treatment or prevention of one or more conditions selected from type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance and hyperglycemia. In addition the present invention relates to methods for preventing or treating of metabolic disorders and related conditions.

Abstract: The invention provides materials and methods for promoting weight loss or preventing weight gain, and in the treatment of diabetes, metabolic syndrome and associated disorders. In particular, the invention provides novel glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.

Abstract: The invention provides materials and methods for promoting weight loss or preventing weight gain, and in the treatment of diabetes, metablic syndrome and associated disorders. In particular, the invention provides novel glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.

Abstract: Methods and compositions are provided for modulating pancreatic islet ?-cell development. Aspects of the methods include promoting ?-cell development by providing agents that promote calcineurin/N FAT signaling, and inhibiting ?-cell development by providing agents that inhibit calcineurin/NFAT signaling. These methods find a number of uses, including, for example, in the treatment of diabetes and human islet diseases. In addition, reagents, devices and kits thereof that find use in practicing the subject methods are provided.

Abstract: This invention relates to compositions for the sustained release of biologically active polypeptides, and methods of forming and using said compositions, for the sustained release of biologically active polypeptides. The sustained release compositions of this invention comprise a biocompatible polymer having dispersed therein, a biologically active polypeptide and a sugar.

Abstract: Provided herein are pharmaceutical and transplant compositions and methods related to the treatment and prevention of diabetes. More specifically, the compositions and methods are related to activation of glial derived neurotrophic factor (GDNF) receptors or overexpression of the GFR-?1/c-Ret receptor complex in insulin secreting cells so as to promote cell survival and proliferation.

Abstract: The invention relates to ALK7 soluble receptors and their uses as antagonists of the function of certain ligands such as GDF-8 (Myostatin) and GDF-11. The ALK7 soluble receptor of the invention is useful as antagonists of GDF-8 and GDF-11 in the treatment of neuronal diseases or conditions such as stroke, spinal cord injury, and all peripheral nerve diseases. The ALK7 soluble receptor of the invention is also useful as GH (growth hormone) equivalent, and for increasing muscle mass.

Abstract: The invention provides with means to predict, in subjects affected by type-2-diabetes (T2D), the probability of developing complications related to the disease. The invention involves (1) identification of genetic features such as single nucleotide polymorphisms (SNPs) for the establishment of a patient profile that can be used for prediction of complications associated with T2D. Signature profiles comprising a combination of SNPs which have greater predictive value for prognosticating particular types of complications, such as, stroke, myocardial infarction and kidney complications associated with T2D are further described. Compositions and kits that can be used with a set of complementary phenotypic markers to evaluate the risk for an individual affected by T2D to develop complications related to the disease and to evaluate the likelihood that an individual affected by type 2 diabetes type will benefit from treatments that collectively aim to reduce the risk of developing such complications.

Abstract: Novel compounds which are antagonists or inverse agonists at one or more of the opioid receptors, pharmaceutical compositions containing them, to processes for their preparation.

Abstract: The invention relates to polypeptides comprising an amino acid sequence which is an analogue of pramlintide, pharmaceutical compositions comprising these polypeptides, and these polypeptides for use as medicaments.

Abstract: The present invention features compositions and methods for treating and preventing a metabolic syndrome featuring the collagen triple helix repeat containing-1 (Cthrc1) protein.

Abstract: The present invention relates to peptide ligands of the melanocortin receptors, in particular the melancortin-4 receptor, and as such, are useful in the treatment of disorders responsive to the activation of this receptor, such as obesity, diabetes mellitus and sexual dysfunction.

Abstract: The invention relates to protracted peptide derivatives such as Glucagon-Like Peptide-1 (GLP-1), exendin-4, and analogues thereof, as well as therapeutic uses thereof. The peptide derivative of the invention comprises a peptide wherein at least one amino acid residue is derivatized with A-B—C—, or A-B—C-D-. These compounds are useful in the treatment or prevention of diabetes type 2 and related diseases. The compounds are potent, have a low ratio of binding affinity to the GLP-1 receptor in the presence of high/low albumin concentrations, have long half-lives, and have a high affinity of binding to albumin, all of which is of potential relevance for the overall aim of achieving long-acting, stable and active GLP-1 derivatives with a potential for once weekly administration.

Abstract: Disclosed herein are improved methods of treating hyperglycemia with a combination of an ultrarapid acting insulin and insulin glargine comprising prandial administration of the ultrarapid insulin, and administration of a first dose of insulin glargine within 6 hours of waking for a day.

Abstract: The present invention relates to compounds of general formula (I), wherein ring A, ring B, R1, R2, R3, Z, and L1 are selected independently of each other and are as defined herein, to compositions comprising the compounds, and methods of using the compounds as glucagon receptor antagonists and for the treatment or prevention of type 2 diabetes and conditions related thereto.

Abstract: Methods for treating type two diabetes mellitus in a subject in need thereof and pharmaceutical compositions for the treatment of type two diabetes mellitus are disclosed. The methods include administering an effective amount of apolipoprotein A-IV to the subject. The pharmaceutical composition includes apolipoprotein A-IV formulated for administration to a subject for the treatment of type two diabetes mellitus. Also disclosed are methods for substantially restoring glucose tolerance in a subject in need thereof to a normal level and methods for lowering blood glucose levels in a subject in need thereof.

Abstract: The present invention provides polypeptide derivatives of IGFBP-3 that are resistant to proteolytic cleavage. These IGFBP-3 derivatives are useful in a variety of therapeutic and diagnostic applications. Also provided are pharmaceutical compositions and kits comprising such IGFBP-3 derivatives and methods for using these derivatives for the treatment of a variety of disorders.

Abstract: Disclosed herein, in certain embodiments, are peptides for use in inhibiting the interactions of PF4 and RANTES. Further disclosed herein, are methods for treating an inflammatory disease, disorder, condition, or symptom. In some embodiments, the method comprises co-administering an agent that inhibits the interactions of PF4 and RANTES and a second active agent.

Abstract: Provided is a modified human tumor necrosis factor receptor-1 polypeptide or a fragment thereof that binds to a tumor necrosis factor in vivo or ex vivo. The modified human tumor necrosis factor receptor-1 polypeptide or fragment exhibits improved ability to bind tumor necrosis factor and resistance to proteases.

Abstract: The present invention provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, wherein A is a five to eight membered monocyclic or a nine to twelve membered bicyclic heterocyclic ring, as further defined herein; Y is S, CH2, or CH; Z is CH or N; R7 and R9 are hydrogen or (C1-C6)alkyl; R2 is (C1-C6)alkoxy, OH, CN, (C1-C6)alkyl, halogen, or CF3; r and s are 0, 1, or 2; and R1 and R3 are as further defined herein. These compounds are agonists, partial agonists and/or modulators of the NPY4 receptor and may be used for the treatment and prophylaxis of obesity, food intake, and other diseases and conditions modulated by the NPY4 receptor.

Abstract: The present invention provides a pharmaceutical composition and a food composition containing tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) as an active ingredient for prevention or treatment of metabolic diseases. The TRAIL according to the present invention can reduce blood glucose, neutral fat, cholesterol, and free fatty acid, and neutral fat in liver, and reduce the synthesis of fat, and promote the lipid metabolism, and thus can be effectively used for the prevention or treatment of metabolic diseases.

Abstract: The present disclosure describes methods for preventing or treating periodontitis or diseases associated with periodontitis. The present disclosure also describes methods of screening for compounds that can be used to prevent or treat periodontitis or diseases associated with periodontitis.

Abstract: This invention discloses GLP-1 analogues and their pharmaceutical salts, wherein the GLP-1 analogue comprises an amino acid sequence of general formula (I), wherein Lys represents a modified lysine with a lipophilic acid. The GLP-1 analogues provided by this invention have the function of human GLP-1, and a longer half-life in vivo compared with the human GLP-1. Uses of such compounds and compositions include treating non-insulin-dependent diabetes, insulin-dependent diabetes, and obesity.

Abstract: The present invention provides fusion proteins comprising a mucin-domain polypeptide covalently linked to an active protein that has improved properties (e.g. pharmacokinetic and/or physicochemical properties) compared to the same active protein not linked to mucin-domain polypeptide, as well as methods for making and using the fusion proteins of the invention.

Abstract: The present invention relates to exendin-4 peptide analogues and their medical use, for example in the treatment of disorders of the metabolic syndrome, including diabetes and obesity, as well as reduction of excess food intake.

Abstract: The present invention is related to compound capable of modulating the activity and/or expression of the protein kinases SCYL1, ADCK1, and GRK5, thereby enhancing the expression and/or release of insulin. The invention is further related to methods of identifying said compounds for the treatment of diseases of the carbohydrate metabolism. The invention is further related to methods of treatment of diseases of the carbohydrate metabolism, particularly diabetes mellitus type 2.

Abstract: The present invention relates to a chimeric protein that includes an N-terminus coupled to a C-terminus, where the N-terminus includes a portion of a paracrine fibroblast growth factor (“FGF”) and the C-terminus includes a C-terminal portion of an FGF19 molecule. The portion of the paracrine FGF is modified to decrease binding affinity for heparin and/or heparan sulfate compared to the portion without the modification. The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, and methods of screening for compounds with enhanced binding affinity for the ?Klotho-FGF receptor complex involving the use of chimeric proteins of the present invention.

Abstract: The present invention relates to a chimeric protein that includes an N-terminus coupled to a C-terminus, where the N-terminus includes a portion of a paracrine fibroblast growth factor (“FGF”) and the C-terminus includes a C-terminal portion of an FGF21 molecule. The portion of the paracrine FGF is modified to decrease binding affinity for heparin and/or heparan sulfate compared to the portion without the modification. The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, and methods of screening for compounds with enhanced binding affinity for the ?Klotho-FGF receptor complex involving the use of chimeric proteins of the present invention.