• Lipodystrophy - A genetic disorder in which the patients do not have the ability to make adipose tissues. As a result, fats are deposited in heart and skeletal muscle. Leptin i.v. treatment could possibly help to clear out some of this fat.
   
• Lipotoxicity, Obesity, and Diabetes - Although that majority of obese individuals show a resistance to Leptin treatments, some genetically obese people respond to Leptin i.v. injections. In these cases, Leptin can be used to remove fats from non-adipose tissues, and possibly to lower lipotoxicity, insulin resistance, and diabetes.  However, recently it has been established that an AMPK-mediated pathway is able to increase glucose uptake and therefore lower insulin resistance.

Figure 14:  AMPK is the mediator of a pathway other than that of insulin that stimulates the uptake of glucose.

By a pathway that is yet unknown, AMPK is able to stimulate and increase in Glut-4 receptors in the membrane.  This results in a greater ability of the cell to take up glucose - and a decrease in the insulin resistance of diabetic individuals.  Therefore, Leptin, which stimulates AMPK, could possibly be used to stimulate glucose uptake.  However, this would probably only work with lean type 2 diabetics, who are not resistant to leptin already.

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 Department of Biochemistry and Molecular Biophysics
krclark@u.arizona.edu