Abstract: Provided are dosage forms of one or more tissue kallikrein-1 (KLK1) polypeptides which have a total KLK1 polypeptide dosage of about 0.1 ?g/kg to about 10.0 ?g/kg, including subcutaneous and intravenous dosage forms. Also provided are related devices and methods of use thereof, for example, for treating ischemic and hemorrhagic conditions.

Abstract: Provided are preparations of tissue kallikrein-1 (KLK1) glycoforms having a defined number of oligosaccharide units per KLK1 molecule. Also provided are mixtures of such glycoforms, pharmaceutical compositions containing such glycoforms or mixtures thereof, methods of obtaining the rhKLK1 glycoforms, and therapeutic uses thereof.

Abstract: Provided are high concentration compositions of tissue kallikrein-1 (KLK1) and methods of parenterally administering such compositions to a subject in need thereof, where absorption into the circulation via, for example, intravenous or subcutaneous administration improves systemic pharmacokinetics, bioavailability, safety, and/or convenience relative to intravenous or other forms of administration. Also provided are recombinant human KLK1 (rhKLK1) polypeptides that can be readily concentrated to high protein concentrations, and substantially pure compositions thereof.

Abstract: Provided are preparations of tissue kallikrein-1 (KLK1) glycoforms having a defined number of oligosaccharide units per KLK1 molecule. Also provided are mixtures of such glycoforms, pharmaceutical compositions containing such glycoforms or mixtures thereof, methods of obtaining the rhKLK1 glycoforms, and therapeutic uses thereof.

Abstract: Embodiments of the present invention relate to compositions and methods of treating patients for type 1 diabetes mellitus (T1D) by administering a therapeutically effective dose of recombinant human KLK1, variants of KLK1, or active fragments thereof. Such patients may be increase risk patients for developing T1D or T1D patients in the Honeymoon Phase. Such treatment may be expected to prevent or delay the onset of T1D, to ameliorate the symptoms of T1D, or to ameliorate the extent to which the T1D manifests.

Abstract: The present invention provides pharmaceutical compositions comprising: (a) a modulator of hepatic parasympathetic tone, (b) at least one diabetes drug, and (c) a pharmaceutically acceptable carrier. The present invention includes methods for the treatment and/or prevention of insulin resistance, type 2 diabetes, impaired glucose intolerance, and other associated disorders with pharmaceutical compositions described herein. The invention also provides for a kit comprising a pharmaceutical composition and instructions for its use.

Abstract: The present invention relates generally to anti-bradykinin B2 receptor (BKB2R) antibodies and methods for making and using them. In particular, the anti-BKB2R antibodies having the variable region sequences described herein are useful for altering one or more of BKB2R of and/or GSK-3 signaling pathways for the treatment of diseases, disorders and conditions such as cancer, diabetes, cardiovascular disorders and other conditions.

Abstract: The present invention relates to pharmaceutical compositions comprising glandular kallikrein in combination with myelin basic protein or copaxone for use in the treatment of multiple sclerosis. The present invention further relates to a method of suppressing autoimmune responses in a patient afflicted with or suffering at least one clinical sign of multiple sclerosis, comprising administering to said patient a therapeutically effective amount of glandular kallikrein in combination with a therapeutically effective amount of myelin basic protein or copaxone.

Abstract: This invention relates to methods of treating Alzheimer's disease or symptoms thereof, and amnesic mild cognitive impairment or symptoms thereof. Methods of the invention include administering a therapeutically effective amount of tissue kallikrein, variants or active fragments thereof. The invention further relates to uses of tissue kallikrein or a variant or active fragment thereof for the digesting or cleaving amyloid and the treatment of conditions benefiting from the digestion or cleavage of amyloid. The invention further relates to pharmaceutical compositions comprising a therapeutically effective amount of tissue kallikrein, variants or active fragments thereof formulated for oral or intranasal administration.

Abstract: Provided is an immunosuppressive peptide of 40 kDa molecular weight, isolated from the submandibular glands (SMG*) of rats, having the capacity to suppress immune reactions upon parenteral administration to rats and mice. The peptide was identified as glandular kallikrein (K1) by partial sequencing and by enzymatic activity. Also provided are methods and compositions for Using K1 peptides in the treatment of autoimmune diseases.

Abstract: Provided herein are methods of treating Parkinson's disease, dementia with Lewy bodies, and conditions associated with Parkinson's disease and dementia with Lewy bodies. These methods include administering to a subject in need thereof a therapeutically effective amount of a tissue kallikrein (KLK1) polypeptide, including active variants and fragments thereof.

Abstract: The invention relates to methods of administering kallikrein, a variant, or active fragment thereof to stimulate proliferation of islet cells generally and ?-cells specifically. The invention also includes compositions to stimulate proliferation in vivo and in vitro.

Abstract: The invention relates to methods of treating Parkinson's disease, dementia with Lewy bodies, and conditions associated with Parkinson's disease and dementia with Lewy bodies. Methods include administering a therapeutically effective amount of tissue kallikrein, variants or active fragments thereof.

Abstract: The invention relates to pharmaceutical compositions comprising tissue kallikrem (TK), and optionally a diabetes drug, a method of screening for a metabolic disorder by determining the concentration of TK and insulin in a biological sample from a test subject, a method of screening for a therapeutic agent for the treatment or prevention of a metabolic disorder, and a method for treating or preventing a metabolic disorder using a pharmaceutical composition comprising TK.

Abstract: The present invention provides pharmaceutical compositions comprising (S)-bethanechol or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier and optionally at least one diabetes drug. The use of said composition in the treatment of insulin resistance, type 2 diabetes, impaired glucose tolerance and related disorders is also provided. The invention also provides for a kit comprising the pharmaceutical compositions and instructions for its use.

Abstract: There is provided a method of reducing insulin resistance in a mammalian patient comprising selecting a patient suffering from insulin resistance and administering a compound which increases hepatic glutathione and a compound which increases hepatic nitric oxide.

Abstract: The present invention provides pharmaceutical compositions comprising: (a) a modulator of hepatic parasympathetic tone, (b) at least one diabetes drug, and (c) a pharmaceutically acceptable carrier. The present invention includes methods for the treatment and/or prevention of insulin resistance, type 2 diabetes, impaired glucose intolerance, and other associated disorders with pharmaceutical compositions described herein. The invention also provides for a kit comprising a pharmaceutical composition and instructions for its use.

Abstract: The present invention provides pharmaceutical compositions comprising antagonists of hepatic sympathetic activity and methods for using said pharmaceutical compositions for treatment of hyperglycemia, hyperinsulinaemia, hyperlipidaemia, hypertriglyceridaemia, diabetes, insulin resistance, impaired glucose metabolism, conditions of impaired glucose tolerance, conditions of impaired fasting plasma glucose, obesity, diabetic retinopathy, diabetic nephropathy, glomerulosclerosis, diabetic neuropathy, syndrome X, renal failure, sexual dysfunction, chronic stress, and anxiety.

Abstract: The present invention provides methods and materials for diagnosing a metabolic disorder comprising measuring insulin and HISS action or alternatively HISS levels, first in a fasting state and again, following consumption of a mixed standard meal. The metabolic disorders diagnosed using the disclosed methods and materials include insulin resistance, pre-diabetes and diabetes. The present invention also provides kits for practicing the disclosed methods.

Abstract: There is provided the use of a phosphodiesterase antagonist to reduce insulin resistance, and to amplify the effect of nitric oxide on skeletal muscle insulin-mediated glucose uptake in a mammal. In some instances, the antagonist is targeted to the liver. In some instances, the insulin resistance is hepatic insulin sensitizing substance (“HISS”) dependant insulin resistance.