Hyperglycaemic clamp and insulin binding to isolated monocytes before and after glibenclamide treatment of mild type II diabetics

The therapeutic action of 3.5 mg glibenclamide (HB 420) once a day for six weeks was evaluated in ten mild NID diabetics previously treated with diet only. Stable HbA₁, insulin secretion during hyperglycaemic clamp (100 mg/dl over the baseline in the first study, and at the same level in the second one), peripheral sensitivity expressed as the amount of dextrose infused per Kg per min (M-coefficient), the glucose metabolic clearance rate (MCR) and the M/I ratio were measured. Circulating monocytes were separated to assess insulin binding before and after treatment. The results included a significant decrease in HbA₁ (7.5 ± 0.3 against 8.4 ± 0.4%, P < 0.005), increased steady-state (100-120 min.) plasma insulin (31 ± 4.4 against 25.7 ± 3.9 μU/ml), a significant increase in M-coefficient (4.02 ± 0.62 against 2.49 ± 0.31 mg/Kg/min, P < 0.01), and MRC (1.90 ± 0.34 against 1.18 ± 0.18 ml/Kg/min, P < 0.025) and an increase in the M/I ratio (14.6 ± 1.9 against 11.2 ± 1.7). All subjects displayed an increase in total insulin binding (4.03 ± 0.31% against 2.79 ± 0.34%, P < 0.001) and affinity constants (K(e) = 8.3 ± 0.6 against 6.6 ± 0.4 x 10⁷M^-1, P < 0.05). Since the M/I ratio increased in only 7/10 subjects and since there was no significant correlation between the percentage increase in M and MCR and the plasma insulin increase, whereas the increase in R₀ was significant, it is felt that the euglycaemizing action of low doses of glibenclamide is primarily peripheral. This action appears to be independent on the B-cell effect and may depend on a direct action on the target cells.