Compositions and methods relating to glucose metabolism, weight control, and food intake

• US 6,861,405 B2
• Filed: 06/11/2002
• Issued: 03/01/2005
• Est. Priority Date: 06/12/2001
• Status: Expired due to Fees

• Current Assignee: Yale University
• Original Assignee: Yale University
• Inventors: Koni, Pandelakis A., Kaczmarek, Leonard, Flavell, Richard A., Xu, Jianchao, Desir, Gary
• Primary Examiner(s): Wax, Robert A.
• Application Number:
  US10/167,528
• Publication Number:
  US 20030032595A1
• Time in Patent Office: 994 Days
• Field of Search: 514/12
• US Class Current: 514/4.8
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/0362 Animal model for lipid/glucose metabolism, e.g. obesity, type-2 diabetes
• CPC Class Codes: A01K 67/0276 Knock-out vertebrates
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/14 Quaternary ammonium compounds, e.g. edrophonium, choline betaines A61K31/205
• CPC Class Codes: A61K 31/277 having a ring, e.g. verapamil
• CPC Class Codes: A61K 31/4045 Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/4174 Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4409 only substituted in position 4, e.g. isoniazid, iproniazid
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/4706 4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
• CPC Class Codes: A61K 31/472 Non-condensed isoquinolines, e.g. papaverine
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 16/28 : against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C12N 15/8509 : for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: G01N 33/5008 : for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/502 : for testing non-proliferative effects
• CPC Class Codes: G01N 33/5044 : involving specific cell types
• CPC Class Codes: G01N 33/5061 : Muscle cells

Abstract

The present invention relates to weight control, control of body fat and food intake, and provides useful methods for treating, inter alia, obesity, diabetes and insulin insensitivity, and conditions, diseases, and disorders relating thereto. The invention also relates to methods of identifying useful compounds relating to weight loss, food intake, diabetes, and obesity, among other things, based on the discovery that inhibiting Kv1.3 activity mediates decreased food intake, weight loss, decreased body fat, increase glucose uptake, and increased insulin sensitivity, among other things.

Claims

1. A method for inducing weight loss in an animal, said method comprising administering to an animal a voltage-gated potassium channel Kv1.3 inhibiting amount of a Kv1.3 inhibitor, wherein said Kv1.3 inhibitor is a chemical compound, wherein said chemical compound is a short scorpion toxin, wherein said short scorpion toxin is margatoxin thereby inducing weight loss in said animal.

2. A method for decreasing body fat in animal, said method comprising administering a Kv1.3 inhibiting amount of a Kv1.3 inhibitor to said animal, wherein said inhibitor is margatoxin, thereby decreasing body fat in said animal.

3. The method of claim 2, wherein said animal is selected from the group consisting of a bird, a rodent, and a mammal, and further wherein said mammal is selected from the group consisting of a cow, a pig, a sheep, a buffalo, a beefalo, a bison, a deer, a goat, and a human.

4. A method for increasing insulin sensitivity in an animal, said method comprising administering a Kv1.3 inhibiting amount of a Kv1.3 inhibitor to an animal, wherein said inhibitor is margatoxin, thereby increasing insulin sensitivity in said animal.

5. A method for decreasing food intake in an animal, said method comprising administering a Kv1.3 inhibiting amount of a Kv1.3 inhibitor to an animal, wherein said inhibitor is margatoxin, thereby decreasing food intake in said animal.

6. A method for affecting appetite in an animal, said method comprising administering a Kv1.3 inhibiting amount of a Kv1.3 inhibitor to an animal, wherein said inhibitor is margatoxin, thereby affecting appetite in said animal.

7. A method for treating obesity in an animal, said method comprising administering a Kv1.3 inhibiting amount of a Kv1.3 inhibitor to an animal, wherein said inhibitor is margatoxin, thereby treating obesity in said animal.

8. A method for preventing obesity in a animal, said method comprising administering a Kv1.3 inhibiting amount of a Kv1.3 inhibitor to an animal, wherein said inhibitor is margatoxin, thereby preventing obesity in said animal.

9. A method for treating a glucose-metabolism disease or disorder in an animal, said method comprising administering a Kv1.3 inhibiting amount of a Kv1.3 inhibitor to an animal, wherein said inhibitor is margatoxin, thereby treating a glucose-metabolism disorder in said animal.

10. The method of claim 9, wherein said glucose-metabolism disease or disorder is selected from the group consisting of obesity, diabetes, insulin resistance, glucose intolerance, hyerinsulinemia, Syndrome X, hypercholesterolemia, hyperlipoproteinemia, hypertriglyceridemia, atherosclerosis, and diabetic renal disease.

11. A method for affecting physical activity in an animal, said method comprising administering a Kv1.3 inhibiting amount of a Kv1.3 inhibitor to an animal, wherein said inhibitor is margatoxin, thereby affecting physical activity in said animal.

12. A method for affecting metabolic rate in an animal, said method comprising administering a Kv1.3 inhibiting amount of a Kv1.3 inhibitor to an animal, wherein said inhibitor is margatoxin, thereby affecting metabolic rate in said animal.