Pharmaceutical compositions and methods for metabolic modulation

Abstract

Pharmaceutical compositions include compounds with cytokinin activity to modulate glucose and / or lipid metabolism in a mammal. Especially preferred compounds include those comprising a purine scaffold, and it is further preferred that contemplated compositions are employed to prevent and / or treat various diseases, including pre-diabetes, insulin resistance, type-2 diabetes, Syndrome X, and dyslipidemia In still further preferred aspects, compounds with cytokinin activity are used to activate AMPK and / or Akt. Consequently, various diseases associated with dysregulation of AMPK and / or Akt may be treated using the compounds of the present inventive subject matter.

Description

[0001] This application claims the benefit of U.S. Provisional Patent Applications Ser. Nos. 60 / 493,447; 60 / 499,637; 60 / 511,746; 60 / 562,384; and 60 / 562,496; which were filed Aug. 8, 2003; Sep. 2, 2003; Oct. 15, 2003; Apr. 14, 2004; and Apr. 14, 2004; respectively, all of which are incorporated by reference herein.FIELD OF THE INVENTION [0002] The field of the invention is pharmaceutical compositions and methods for metabolic modulation. BACKGROUND OF THE INVENTION [0003] Pre-diabetes, insulin resistance, type-2 diabetes (non-insulin dependent diabetes, NIDDM), syndrome X, and dyslipidemia pose a substantial health threat to a significant portion of the population in the US and other industrialized nations. [0004] For example, about 6.3% of all US citizens are diagnosed with diabetes, and another 5.2 million people are suspected to be undiagnosed (National diabetes fact sheet: General information and national estimates on diabetes in the United States, 2003. Rev ed. Atlanta, Ga.: U.S...

AI Technical Summary

Benefits of technology

[0019] Thus, while numerous compositions and methods for metabolic control are known in the art, all or almost all of them, suffer from one or more disadvantages. Similarly, numerous uses for cytokinins are known in the art. However, none of th

Problems solved by technology

Pre-diabetes, insulin resistance, type-2 diabetes (non-insulin dependent diabetes, NIDDM), syndrome X, and dyslipidemia pose a substantial health threat to a significant portion of the population in the US and other industrialized nations.

Unfortunately, many biguanides also produce lactic acidosis, which may become a life-threatening condition, especially where a patient has renal insufficiency.

Still further, biguanide therapy is often counter-indicated where a patient takes other drugs that interfere with renal function.

However, various glitazones have been withdrawn from the market or development has discontinued due to relatively high hepatotoxicity.

Moreover, numerous other side effects include weight gain and fluid retention.

Worse yet, tolbutamide (a sulfonylurea) was shown to increase the risk of cardiovascular mortality, which may also be the case in other sulfonylureas and meglitinides due to their common mode of action.

However, while some disadvantages may be mitigated, other disadvantages nevertheless remain.

There are numerous insulin formulations known in the art (e.g., fast acting, intermediate acting, long acting), and depending on the type of insulin, problems may arise with immunogenicity, tolerability, and / or long-term effectiveness.

Furthermore, correct administration of such preparations must be verified via blood tests that add to the inconvenience of such therapy.

However, at least some of these nutritional supplements exhibit significant toxicity (e.g., Cr-picolinate), and / or the chromium has only relatively low solubility and / or bioavailability.

However, to achieve substantial normalizing effect, at least some forms of such products need to be ingested at rather large amounts.

However, such claims are typically not verified or endorsed by the FDA, and the efficacy for the advertised purpose is questionable for all or almost all of these supplements.

Thus, while numerous compositions and methods for metabolic control are known in the art, all or almost all of them, suffer from one or more disadvantages.

However, none of the known methods teaches or suggests use of cytokinins for specific metabolic modulation.

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