Hepatic insulin sensitizing substance and test meal for insulin sensitization
Inventors
Assignees
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Publication Number
US-9840547-B2
Publication Date
2017-12-12
Expiration Date
Abstract
The present invention provides methods of treating prediabetes, hyperglycemia, type 2 diabetes, AMIS syndrome, and obesity in a subject by administering to the patient HISS. The present invention also provides methods of diagnosing AMIS syndrome in a patient. Additionally, the present invention provides a method of shifting nutrient storage in meat-producing livestock to muscle rather than fat.
Core Innovation
The invention relates to identification and characterization of Hepatic Insulin Sensitizing Substance (HISS) as a nitrosylated peptide. HISS is described as a 29-amino acid peptide (SEQ ID NO:1) nitrosylated at cysteine residues 7 and 19.
The invention further describes the role of HISS in meal-induced insulin sensitization (MIS/AMIS). HISS is proposed to be involved in insulin sensitization in connection with a meal and is characterized with respect to identity, stability, kinetics, molecular weight, and disulfide and nitrosylation features.
The invention also describes therapeutic use of HISS for prediabetes/hyperglycemia/type 2 diabetes, AMIS syndrome, and obesity. The therapeutic use is described for administering HISS alone or with insulin, and for shifting nutrient storage in livestock toward muscle.
Additionally, the invention describes diagnostic approaches using a standardized soy-milk/glucose test meal and measurement of HISS levels after fasting and feeding, optionally in combination with insulin/glucose. Experimental evidence described in the content includes confirmation of HISS identity and nitrosylation features and effects on glucose uptake and protein synthesis in vitro.
Claims Coverage
The independent claim covers a pharmaceutical composition formulation that includes an isolated nitrosylated peptide or protein sequence based on SEQ ID NO: 2, together with a pharmaceutically acceptable carrier selected from a specified list. The claim includes nitrosylation at one or more cysteine residues corresponding to cysteine residues 7 and 19, and the dependent claim further specifies nitrosylation at both cysteine residues 7 and 19.
Nitrosylated peptide or protein based on SEQ ID NO: 2
An isolated peptide or protein consisting of the amino acid sequence of SEQ ID NO: 2 or an amino acid sequence having at least 90% identity therewith, wherein said peptide or protein is nitrosylated at one or more of cysteine residues 7 and 19 of SEQ ID NO: 2.
Pharmaceutical composition with pharmaceutically acceptable carrier
A pharmaceutical composition further comprising a pharmaceutically acceptable carrier with the carrier selected from the group consisting of bacteriostatic water, phosphate buffered saline, ethanol, a polyol, microcrystalline cellulose, gelatin, magnesium stearate, synthetic solvents, ethylene vinyl acetate, polyanhydrides, polyglycolic acid, polyoorthoesters, polylactic acid and a combination thereof.
Nitrosylation at both cysteine residues 7 and 19
The composition wherein the peptide or protein is nitrosylated at cysteine residues 7 and 19 of SEQ ID NO: 2.
Overall, the claim set is directed to a pharmaceutical composition containing an isolated SEQ ID NO:2-based peptide or protein with nitrosylation on cysteine residues corresponding to residues 7 and 19, formulated with a carrier chosen from a defined excipient list.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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