Effect of sulfonylurea agents on pyruvate dehydrogenase activity in circulating lymphocytes from patients with non-insulin-dependent diabetes mellitus (NIDDM).
In circulating lymphocytes from patients with non-insulin-dependent diabetes mellitus (NIDDM) subnormal pyruvate dehydrogenase (PDH) activity returns to normal following patient treatment with sulfonylurea (gliclazide, 80 mg twice daily/5 weeks). Moreover, in vitro in cells from diabetic patients exposed to insulin at 50 microU/mL PDH activation also occurs; in cells of controls the same happens for insulin at 5 microU/mL, whereas at 50 microU/mL inhibition takes place. Therefore, the low PDH activity in cells of NIDDM patients might be caused by defective insulin control on the enzyme and its recovery in gliclazide-treated patients by drug-mediated removal of the defect. The validity of the hypothesis was verified in this study where cells of NIDDM patients before and after gliclazide treatment were exposed, in vitro, to insulin at 5 and 50 microU/mL and then tested for PDH activity. In such conditions, the profile of PDH behavior in treated patients was no longer comparable to that in untreated patients but closer to that in euglycemic controls, thus supporting the view that the recovery of PDH activity in NIDDM patients following gliclazide treatment might be the expression of an additional effect that the drug would have in these patients, aimed to renew cell responsiveness to insulin.
Dipartimento di Medicina e Oncologia Sperimentale, Università di Torino, Italia.
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Rinaudo
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Piccinini
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Gamba
D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D005907:Gliclazide / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D011768:Pyruvate Dehydrogenase Complex / Q000097:blood*; D012016:Reference Values
D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D005907:Gliclazide