Sulfonylureas in Insulin-Dependent (Type I) Diabetes: Evidence for an Extrapancreatic Effect in Vivo*

Abstract

The effect of glibenclamide treatment on insulin-mediated glucose disposal was studied in eight C-peptide-negative type I diabetic patients. The patients were studied twice by the euglycemic insulin clamp technique. One of the two experiments was preceded by glibenclamide treatment at the dose of 5 mg, three times daily for 15 days; half of the patients had the first test before and the second test after sulfonylurea treatment, and vice versa. Insulin was infused for four periods of 2 h each sequentially at 0.5, 1.0, 2.0, and 5.0 mU kg-1 min-1; for each insulin infusion period, the steady state plasma free insulin levels were comparable with or without glibenclamide. The mean +/- SEM plasma glucose concentration was 88 +/- 2 mg/dl in both experiments. The insulin-mediated glucose disposal rate was greater with glibenclamide during the first insulin infusion period (which generated plasma free insulin levels within the physiological range) 2.68 +/- 0.32 mg kg-1 min-1 with glibenclamide vs. 1.97 +/- 0.20 mg kg-1 min-1 without glibenclamide (P less than 0.005). However, glucose disposal rates did not differ in the diabetic patients with or without glibenclamide treatment during the second, third, and fourth insulin infusion periods, which generated plasma free insulin levels in the supraphysiological range. These results provide evidence for an extrapancreatic effect of glibenclamide at low insulin concentrations during euglycemic clamping in patients with insulin-dependent diabetes mellitus. However, this effect was not reflected clinically in either an increased rate of hypoglycemic reactions or decreased insulin needs during the short term period of treatment.

Immunohistochemistry, histopathology, and biomarker studies of swertiamarin, a secoiridoid glycoside, prevents and protects streptozotocin-induced β-cell damage in Wistar rat pancreas

“…Glibenclamide, basically a sulfonyl urea, stimulates insulin secretion from β-cells and exerts a control on the blood glucose levels in diabetic rats [50]. The effect of glibenclamide treatment on insulin-mediated glucose disposal was demonstrated in type I diabetic patients and found to be greater with glibenclamide [51]. Since we decided to study the effect of swertiamarin on insulin stimulation, we used glibenclamide as a reference drug.…”

Diabetes-Old Therapies Revisited

“…The effect of glucose-lowering stems essentially from the stimulation of insulin secretion, but there are extra-pancreáticos effects [32], such as reduced clearance of insulin (no-observedeffect with glibenclamide); reduction of glucagon (probably subsequent to stimulation of insulin secretion) and increased insulin sensitivity (small to be clinically significant effect).…”

Immunologic and Genetic Factors in Type 1 Diabetes Mellitus

“…Sulfonylureas, such as glipizide and glimepiride, are considered hypoglycemic agents because they stimulate the release of insulin from beta-cells in the pancreas, thus reducing blood glucose levels (Pernet, Trimble et al 1985). The most common side effect associated with sulfonylureas is hypoglycemia (abnormally low blood glucose levels), which occurs most often in elderly patients who have impaired liver or kidney function.…”