Short Communucations Does Glucagon Preserve its Insulinogenic Effect During Tolbutamide-Induced Hypoglycemia?
Introduction Glucagon is usually contra-indicated in cases of severe sulfonylurea-induced hypoglycemia (Samols, Marri and Marks 1966). However, the observations published on this subject are contradictory (Galloway 1968; Marri, Cozzolino and Palumbo 1968; Davies 1968). Several studies have demonstrated that hypoglycemia, whether insulin-induced or caused by fasting associated with an ethanol perfusion, blocks the insulinogenic effect of both tolbutamide and glucagon (Widstrom and Cerasi 1973; Goldfine, Cerasi and Luft 1972; Oakley, Harrigan, Kissebah and Adams 1972). However, as far as we know, the effect of tolbutamide-induced hypoglycemia upon the insulinogenic effect of glucagon has not been studied previously. We therefore decided to compare the insulinogenic effect of glucagon during insulin-induced hypoglycemia and tolbutamide-induced hypoglycemia. Subjects and Methods The six subjects were healthy volunteers from our department's medical staff, 25 to 45 years of age. None of them had a family history of diabetes mellitus. All had normal body weight, normal plasma lipid concentrations and normal carbohydrate tolerance. All the tests were performed after an overnight twelve-hour fast and a thirtyminute rest in the reclining position. Each subject had two intra-venous catheters for injections and blood-sampling.
injection of minutes later Laboratory). tration were injection.
The first test consisted of a two-minute intra-venous 1 g of tolbutamide (Hoechst Laboratory), followed 20 by an intra-venous injection of 0.5 mg of glucagon (Novo Glycemia, insulinemia and C-peptide plasma concenmeasured 0, 6, 20, 26 and 40 minutes after the initial
The second test consisted of an intra-venous injection of 0.03 U/kg of Actrapid H.M. (Novo Laborataory), followed 20 minutes later by an intra-venous injection of 0.5 mg of glucagon. Glycemia and C-peptide plasma concentration were measured 0, 20, 26 and 40 minutes after the initial injection. The tests were carried out with a 15 day interval. Statistics The statistical analysis used the Student's t-test, comparing pairs of samples and the mean value of each distribution (considered normal). Results The hypoglycemic nadir was identical in both tests: 2.4±0.5mmol/l (ranging from 1.6 to 3.4mmol/l) with tolbutamide versus 2.2+0.4 mmol/1 (ranging from 1.7 to 2.9mmol/l) with insulin.
Horm. metab. Res. 24 (1992) 541-542 © Georg Thieme Verlag Stuttgart • New York
Troupel2
With tolbutamide, we observed: The initial insulinemia was 5.4±2u.U/ml, the initial C-peptide plasma levels were 1.6 + 0.3 ng/ml, while the average glycemia was 4.8 ± 0.05 mmol/1. Six minutes after the tolbutamide injection, insulinemia reached a plasma level peak of 45 + 14 u,U/ml (the C-peptide plasma concentration was then 4.7 + 0.7 ng/ml). The C-peptide plasma concentration dropped to 3.8 + 0.7 ng/ml at the twentieth minute of the test. Six minutes after the glucagon injection, insulinemia reached a second plasma level peak of 68±36u.U/ml, with a C-peptide plasma concentration of 5.8 ±1.9ng/ ml, while the mean glycemia was 3.1 ±0.8 mmol/1 (ranging from 2.4 to 4.3mmol/1). The increase of 2 ± 1.3 ng/ml in C-peptide plasma concentration was significant (p< 0.001). With insulin, we observed: The initial C-peptide plasma concentration was 1.6 + 0.4 ng/ml, with a mean glycemia of 4.8 ±0.08 mmol/1. The C-peptide plasma concentration 20 minutes after the insulin injection was significantly lower 0.9±0.3 ng/ml (p < 0.001). Six minutes after the glucagon injection, the C-peptide plasma concentration was only 1.5 + 1 ng/ml, with a mean glycemia of 2.9 ± 0.7mmol /l (ranging from 2 to 3.6 mmol/1). The increase in C-peptide plasma concentration (of 0.63 ±0.82 ng/ml) was not considered significant (p
Introduction Glucagon is usually contra-indicated in cases of severe sulfonylurea-induced hypoglycemia (Samols, Marri and Marks 1966). However, the observations published on this subject are contradictory (Galloway 1968; Marri, Cozzolino and Palumbo 1968; Davies 1968). Several studies have demonstrated that hypoglycemia, whether insulin-induced or caused by fasting associated with an ethanol perfusion, blocks the insulinogenic effect of both tolbutamide and glucagon (Widstrom and Cerasi 1973; Goldfine, Cerasi and Luft 1972; Oakley, Harrigan, Kissebah and Adams 1972). However, as far as we know, the effect of tolbutamide-induced hypoglycemia upon the insulinogenic effect of glucagon has not been studied previously. We therefore decided to compare the insulinogenic effect of glucagon during insulin-induced hypoglycemia and tolbutamide-induced hypoglycemia. Subjects and Methods The six subjects were healthy volunteers from our department's medical staff, 25 to 45 years of age. None of them had a family history of diabetes mellitus. All had normal body weight, normal plasma lipid concentrations and normal carbohydrate tolerance. All the tests were performed after an overnight twelve-hour fast and a thirtyminute rest in the reclining position. Each subject had two intra-venous catheters for injections and blood-sampling.
injection of minutes later Laboratory). tration were injection.
The first test consisted of a two-minute intra-venous 1 g of tolbutamide (Hoechst Laboratory), followed 20 by an intra-venous injection of 0.5 mg of glucagon (Novo Glycemia, insulinemia and C-peptide plasma concenmeasured 0, 6, 20, 26 and 40 minutes after the initial
The second test consisted of an intra-venous injection of 0.03 U/kg of Actrapid H.M. (Novo Laborataory), followed 20 minutes later by an intra-venous injection of 0.5 mg of glucagon. Glycemia and C-peptide plasma concentration were measured 0, 20, 26 and 40 minutes after the initial injection. The tests were carried out with a 15 day interval. Statistics The statistical analysis used the Student's t-test, comparing pairs of samples and the mean value of each distribution (considered normal). Results The hypoglycemic nadir was identical in both tests: 2.4±0.5mmol/l (ranging from 1.6 to 3.4mmol/l) with tolbutamide versus 2.2+0.4 mmol/1 (ranging from 1.7 to 2.9mmol/l) with insulin.
Horm. metab. Res. 24 (1992) 541-542 © Georg Thieme Verlag Stuttgart • New York
Troupel2
With tolbutamide, we observed: The initial insulinemia was 5.4±2u.U/ml, the initial C-peptide plasma levels were 1.6 + 0.3 ng/ml, while the average glycemia was 4.8 ± 0.05 mmol/1. Six minutes after the tolbutamide injection, insulinemia reached a plasma level peak of 45 + 14 u,U/ml (the C-peptide plasma concentration was then 4.7 + 0.7 ng/ml). The C-peptide plasma concentration dropped to 3.8 + 0.7 ng/ml at the twentieth minute of the test. Six minutes after the glucagon injection, insulinemia reached a second plasma level peak of 68±36u.U/ml, with a C-peptide plasma concentration of 5.8 ±1.9ng/ ml, while the mean glycemia was 3.1 ±0.8 mmol/1 (ranging from 2.4 to 4.3mmol/1). The increase of 2 ± 1.3 ng/ml in C-peptide plasma concentration was significant (p< 0.001). With insulin, we observed: The initial C-peptide plasma concentration was 1.6 + 0.4 ng/ml, with a mean glycemia of 4.8 ±0.08 mmol/1. The C-peptide plasma concentration 20 minutes after the insulin injection was significantly lower 0.9±0.3 ng/ml (p < 0.001). Six minutes after the glucagon injection, the C-peptide plasma concentration was only 1.5 + 1 ng/ml, with a mean glycemia of 2.9 ± 0.7mmol /l (ranging from 2 to 3.6 mmol/1). The increase in C-peptide plasma concentration (of 0.63 ±0.82 ng/ml) was not considered significant (p
