Insulin and IGF1 receptor function among type II diabetic responders and nonresponders to glyburide.
This study evaluated the insulin and insulin-like growth factor-1 (IGF-1) receptor function among patients with type II diabetes who did or did not respond to 1 month of treatment with the oral sulfonylurea agent glyburide. Patients with type II diabetes were initially placed on dietary treatment alone. Patients whose fasting plasma glucose level exceeded 9 mmol/L were enrolled in a prospective 1-month trial of oral glyburide. Clinical, laboratory, and receptor characteristics were assessed before and after glyburide therapy and were compared between the responders and non-responders as well as with matched nondiabetic control subjects. Of the 34 patients who participated in the study, 17 (50%) responded (fasting plasma glucose decreased to 7.8 mmol/L or by 30% from basal level) to the drug. There were no clinical parameters that could distinguish between patients responding and not responding to glyburide. Iodine 125-labeled insulin binding to intact erythrocytes tended to be higher among responders both before and after glyburide. However, the studies of specific insulin binding and insulin receptor tyrosine kinase activities of purified erythrocyte receptors could not distinguish between the two groups of patients with diabetes either before or after glyburide treatment. Compared with weight-matched nondiabetic controls, the erythrocyte insulin receptor tyrosine kinase activity in the patients with diabetes was significantly (by about 45%) decreased. Studies of the IGF-1 receptor likewise did not reveal differences between the two diabetic groups. In conclusion, one half of ambulatory patients with type II diabetes showed a satisfactory hypoglycemic response to a short-term glyburide treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Grunberger
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Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201.
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D005905:Glyburide / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000502:physiology*; D011972:Receptor, Insulin / Q000187:drug effects / Q000502:physiology*
D001786:Blood Glucose; D007328:Insulin; D011505:Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D005905:Glyburide