Glybenclamid (HB 419) and the Prediabetes of Subtotally Pancreatectomized Rats[*]

Abstract

Wistar albino male rats with a body weight between 80-100 g and an age of 36-40 days were submitted to a subtotal pancreatectomy (95 %). The subtotal pancreatectomy is followed by a prediabetic period of 3--4 weeks duration, where the basal blood glucose is normal, the i.v. glucose tolerance test pathological, basal IMI lower than normal and no insulin release after i.v. glucose load. One group of rats was treated orally immediately after operation with HB 419 (Glybenclamid) 1 mg/kg body weight, dissolved in water.

Results: 1) The increase in body weight of partially pancreatectomized rats can be normalized by administration of HB 419. 2) 14 days after operation in partially pancreatectomized rats there is an increase in blood glucose level 7 hours after food intake. 3) The amount of immunlogical measurable insulin in blood decreases to about half of the initial value after 3 weeks, and after a 4-weeks-treatment the IMI-level amounts to almost double the initial level. 4) In partially pancreatectomized rats after i.v. glucose injection there is no reactive insulin response. Treatment with HB 419 does not affect these phenomena. Our results indicate that HB 419 as well as the other sulfonylurea have an influence on the islet cell system, however, on the whole they stimulate only basal insulin secretion. Reactivity of B-cells to an increase in glucose concentration in arterial blood is not changed.

Key words

Glybenclamid - HB 419 - Subtotal Pancreatectomy - Glucose Tolerance Test - Insulin - Sulfonylureas - Hexokinase

1 This paper was first presented at the Rottach-Egern-Symposium on HB 419, January 27-29, 1969

1 This paper was first presented at the Rottach-Egern-Symposium on HB 419, January 27-29, 1969

2 Supported by a grant from the Deutsche Forschungsgemeinschaft, Bad Godesberg, Germany.