From: young@clpd.kodak.com (Rich Young)
Subject: Obesity and Type II diabetes
Originator: young@plasma
Reply-To: young@clpd.kodak.com
Organization: Clinical Diagnostics Division, Eastman Kodak Company
Date: Wed, 6 Jan 93 01:18:05 GMT

   The following article is taken from SCIENCE NEWS, 143(1):7 and is quoted
   without permission:

           "Roughly 90 percent of diabetics suffer from a form of the
        disease described as Type II, or non-insulin-dependent.  Though
        obesity constitutes one of the most common predisposing factors
        for this type of diabetes, clinicians have never known why.  Now
        a trio of Boston-based researchers has uncovered surprising
        clues -- opening up the prospect of managing this often lethal
        disease more effectively with drugs.
           In the January 1st SCIENCE, Bruce M. Speigelman and his
        colleagues at the Dana-Farber Cancer Institute report on animal
        studies showing that obesity somehow stimulates fat cells to
        overproduce a hormone-like substance known as tumor necrosis
        factor-alpha (TNF-alpha).
           Compared to lean rodents, obese animals of the same strain
        showed a sharp elevation in the activity of genes responsible
        for producing TNF-alpha.  Not only did obese animals have more
        fatty tissue to make the compound, but each of their fat cells
        secreted about twice as much of the hormone-like substance as
        did those of lean cohorts.  This trend held up in at least four
        animal models of obesity: all four generally express insulin
        resistance and other symptoms of developing or mature diabetes.
           High levels of TNF-alpha have been shown capable of causing
        both septic shock and a wasting syndrome common in cancer
        victims.  But Speigelman's team now reports finding that a much
        smaller excess of TNF-alpha depresses the expression of genes
        responsible for producing the proteins adipsin and glut4.
           Though adipsin's function remains unknown, Speigelman notes
        that glut4 enables glucose to pass through cell membranes under
        the regulation of insulin.  Indeed, work by him and others has
        shown that the activity of the genes coding for these proteins
        is typically low in animals suffering from obesity-linked
        insulin-resistant syndromes.
           The Dana-Farber scientists also showed that when TNF-alpha's
        effects are blocked with a drug that binds to and disarms the
        molecule, obese animals immediately experience a remarkable
        increase in their responsiveness to insulin.  A primary feature
        of obesity-linked diabetes is the patient's resistance to insulin,
        the chief hormone responsible for lowering concentrations of
        sugar in the blood.
           Speigelman says that, taken together, these new data suggest
        that if obese diabetics similarly overproduce TNF-alpha, clinicians
        may eventually be able to control a patient's blood sugar concen-
        trations with drugs that block TNF-alpha.  Several such drugs are
        currently under development for treating septic shock."


-Rich Young (These are not Kodak's opinions.)