Abstract: Provided herein are cell-based bioassays for measuring GLP-I receptor agonist activity of test compounds, such as GLP-I receptor agonist compounds. Exemplary GLP-I receptor agonist compounds include exendins, exendin analogs, GLP-1(7-37), and GLP-1(7-37) analogs. The bioassays are useful for quantitatively determining cAMP generated in samples containing GLP-I receptor agonist compounds (e.g., exenatide) and 6-23 (clone 6) cells having GLP-I receptors, whereby the amount of cAMP generated can be correlated to the GLP-I receptor agonist activity of the GLPI receptor agonist compounds (e.g., exenatide). Suitable cell-based bioassays include enzyme-linked immunosorbent assays and homogeneous time-resolved fluorescence assays.

Abstract: The present invention relates to novel Pancreatic Polypeptide Family (“PPF”) polypeptides. The PPF polypeptides of the invention generally include at least two PPF motif, have at least 50% sequence identity to PYY (3-36) over its length and will generally retain, at least in part, a biological activity of a PP, PYY or NPY. Preferred PPF polypeptides of the invention are those having a potency in one of the assays described herein (preferably food intake, gastric emptying, pancreatic secretion, or weight reduction assays) which is greater than the potency of PP, NPY, PYY, or PYY(3-36) in that same assay. In one aspect, the PPF polypeptides of the invention include novel PYY analog polypeptides. In another aspect, the PPF polypeptides of the invention include PPF chimeric polypeptides including a fragment of a PP family polypeptide linked to a second PP family polypeptide, wherein each of the first and second fragments includes a PPF motif.

Abstract: Peptide-peptidase inhibitor conjugate molecules and methods of manufacture thereof are disclosed. These conjugate molecules are useful as agents for the treatment and prevention of metabolic and cardiovascular diseases, disorders, and conditions. Such diseases, conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, insulin-resistance, obesity, and diabetes mellitus of any kind, and other diabetes-related disorders.

Abstract: The present invention relates to novel compounds having a function of a peptide in the amylin family, related nucleic acids, expression constructs, host cells, and processes production of the compounds. The compounds of the invention include one or more amino acid sequence modifications. In addition, methods and compositions are disclosed to treat and prevent metabolic disorders such as obesity, diabetes, and increased cardiovascular risk.

Abstract: Hibernating myocardium is characterized by viable myocardium with impaired function due to localized reduced perfusion. Hibernating myocytes retain cellular integrity, but cannot sustain high-energy requirements of contraction. High plasma levels of catecholamines, such as norepinepherine, are believed to be predictive of mortality from hibernating myocardium. Likewise, high levels of catecholamines lead to cardiomyopathy in patients with diabetes. GLP-1 reduces plasma norepinepherine levels, and it thus is useful in a method of treating hibernating myocardium or diabetic cardiomyopathy.

Abstract: The disclosure provides chimeric polypeptides and nucleic acid molecules encoding chimeric polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including lipodystrophy, dyslipidemia, hyperlipidemia, overweight, obesity, hypothalamic amenorrhea, Alzheimer's disease, leptin deficiency, fatty liver disease or diabetes (including type I and type II). Additional diseases and disorders which can be treated by the compounds and methods described herein include nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), metabolic syndrome X and Huntington's Disease.

Abstract: The present invention relates to altering the concentration of fibrinogen, specifically, for example, by decreasing fibrinogen concentration. The present invention also relates to methods for improving the cardiovascular risk profile of a subject by decreasing fibrinogen concentration.

Abstract: The present invention relates generally to novel GIP analogs and GIP hybrid polypeptides with selectable properties, useful as agents for the treatment and prevention of metabolic diseases and disorders, for example those which can be alleviated by control plasma glucose levels, insulin levels, and/or insulin secretion, positive inotropic effects, reduction of catabolic effects, slowing of gastric emptying. Such conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, critical care, insulin-resistance, obesity, and diabetes mellitus of any kind, including type 1, type 2, and gestational diabetes.

Abstract: The present invention relates generally to novel GIP analogs and GIP hybrid polypeptides with selectable properties, useful as agents for the treatment and prevention of metabolic diseases and disorders, for example those which can be alleviated by control plasma glucose levels, insulin levels, and/or insulin secretion, positive inotropic effects, reduction of catabolic effects, slowing of gastric emptying. Such conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, critical care, insulin-resistance, obesity, and diabetes mellitus of any kind, including type 1, type 2, and gestational diabetes.

Abstract: Methods and compositions for treating psychiatric diseases and disorders are disclosed. The methods provided generally involve the administration of an amylin or an amylin agonist to a subject in order to treat psychiatric diseases and disorders, and conditions associated with psychiatric diseases and disorders.

Abstract: The disclosure provides GLP-1 receptor agonist compounds having stabilized regions corresponding to alpha-helical regions of the natural peptide compounds. The disclosure also provides benzamide-containing exendin-4 analogs and alkene-constrained exendin-4 analogs, both of which have stabilized regions corresponding to alpha-helical regions of exendin-4.

Abstract: The disclosure provides the use of GLP-1 receptor agonist compounds to treat pancreatitis (e.g., acute, chronic, hemorrhagic, necrotizing) in patients. The disclosure also provides the use of GLP-1 receptor agonist compounds to reduce elevated plasma amylase and/or lipase concentrations in patients. An exemplary GLP-1 receptor agonist compound is exenatide.

Abstract: Provided herein are pharmaceutical formulations containing exendins, exendin agonists, or exendin analog agonists that are administered at therapeutic plasma concentration levels over a sustained period of time to lower total cholesterol levels; to lower LDL-cholesterol levels; to lower triglyceride levels; to treat dyslipidemia; to treat and slow the progression of atherosclerosis; and to treat, prevent, and reduce the risk of heart attacks and strokes in patients. In the pharmaceutical formulations and methods of the invention, the exendin may be exendin-4, an exendin-4 agonist, or an exendin-4 analog agonist. The pharmaceutical formulations may be polymer-based pharmaceutical formulations that may be administered once weekly. An exemplary pharmaceutical formulation comprises 5% (w/w) of exenatide, about 2% (w/w) of sucrose, and about 93% (w/w) of a poly(lactide-co-glycolide) polymer, wherein the poly(lactide-co-glycolide) polymer is in the form of microshperes encapsulating the exenatide.

Abstract: Novel modified exendins and exendin agonists having an exendin or exendin agonist linked to one or more polyethylene glycol polymers, for example, and related formulations and dosages and methods of administration thereof are provided. These modified exendins and exendin agonists, compositions and methods are useful in treating diabetes and conditions that would be benefited by lowering plasma glucose or delaying and/or slowing gastric emptying or inhibiting food intake.

Abstract: The present invention provides novel Pancreatic Polypeptide Family (“PPF”) polypeptides and methods for their use.

Abstract: Methods for treating obesity or obesity related disorders are disclosed. These methods include the use of anti-obesity agents directed to the forebrain in combination with anti-obesity agents directed to the hindbrain.

Abstract: Compositions of the invention, including compounds that bind to a receptor for a glucagon-like peptide-1, an incretin, a glucagon-like peptide-1 (GLP-1), an exendin, or an agonist, an analog (preferably an agonist analog), a derivative, or a variant of any of aforementioned compounds, are used in the prevention and treatment of arrhythmias associated with cardiac ischemia, cardiac ischemia-perfusion and/or congestive heart failure. The invention relates to both the method and compositions for such treatment.

Abstract: The present invention relates generally to the novel use of incretin compounds (ICs) and amylinomimetic compounds to treat, prevent, or ameliorate a variety of metabolic conditions or diseases.

Abstract: Methods and compositions for treating psychiatric diseases and disorders are disclosed. The methods provided generally involve the administration of an amylin or an amylin agonist to a subject in order to treat psychiatric diseases and disorders, and conditions associated with psychiatric diseases and disorders.

Abstract: Provided herein are cell-based bioassays for measuring GLP-I receptor agonist activity of test compounds, such as GLP-I receptor agonist compounds. Exemplary GLP-I receptor agonist compounds include exendins, exendin analogs, GLP-1(7-37), and GLP-1(7-37) analogs. The bioassays are useful for quantitatively determining cAMP generated in samples containing GLP-I receptor agonist compounds (e.g., exenatide) and 6-23 (clone 6) cells having GLP-I receptors, whereby the amount of cAMP generated can be correlated to the GLP-I receptor agonist activity of the GLP-I receptor agonist compounds (e.g., exenatide). Suitable cell-based bioassays include enzyme-linked immunosorbent assays and homogeneous time-resolved fluorescence assays.