Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of obesity and diabetes has been dramatically increasing during the last decade suggesting a greater patient need for more efficacious and safer drugs. Large molecule therapy has played an important role in diabetes since the discovery of insulin. This legacy was continued upon the introduction of Humulin (first recombinant insulin), Humalog (first engineered insulin) and Byetta (first incretin mimetic). Several other protein therapeutics, such as leptin, adiponectin, bone morphogenic protein-9 and others, are currently in or considered for therapeutic development. Among them, FGF21 is one of the most promising candidates given its outstanding pharmacologic benefits for nearly each and every abnormality of a metabolic disease and lack of apparent side effects in a variety of animal models. Thus, FGF21 represents a novel and appealing therapeutic reagent for Type 2 diabetes mellitus, obesity, dyslipidemia, cardiovascular and fatty liver diseases. The in vitro biology, genetic animal models and in vivo pharmacology of FGF21 will be discussed in this chapter.
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PMID:FGF21 as a therapeutic reagent. 2239 72

Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca(2+)-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP.
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PMID:Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging. 2565 89