title: The use of tolbutamide-induced hypoglycemia to examine the intraislet role of insulin in mediating glucagon release in normal humans.
abstract: Disruption of intraislet mechanisms could account for the impaired glucagon response to hypoglycemia in type 1 diabetes. However, in contrast to animals, there is conflicting evidence that such mechanisms operate in humans. We have used i.v. tolbutamide (T) (1.7 g bolus + 130 mg/h infusion) to create high portal insulin concentrations and compared this with equivalent hypoglycemia using an i.v. insulin infusion (I) (30 mU/m2 x min). Ten normal subjects underwent two hypoglycemic clamps; mean glucose; I (53 +/- 1 mg/dL); and T (53 +/- 1 mg/dL) (2.9 +/- 0.04 mmol/L vs. 2.9 +/- 0.05 mmol/L), held for 30 min. During hypoglycemia, mean peripheral insulin levels were greater with I (59 +/- 4 mU/L) than T (18 +/- 3 mU/L), P < 0.001. Calculated peak portal insulin concentrations were greater during T (282 +/- 28 mU/L) than I (78 +/- 4 mU/L), P < 0.00005. The demonstration of a reduced glucagon response during T-induced hypoglycemia (111 +/- 8 ng/L vs. 135 +/- 12 ng/L, P < 0.05) with higher portal insulin concentrations suggests that intraislet mechanisms may contribute to the release of glucagon during hypoglycemia in man.
authors.affiliation: University Department of Medicine, Northern General Hospital, Sheffield, United Kingdom.
authors.forename: S R
authors.initials: SR
authors.lastname: Peacey
authors.forename: A
authors.initials: A
authors.lastname: Rostami-Hodjegan
authors.forename: E
authors.initials: E
authors.lastname: George
authors.forename: G T
authors.initials: GT
authors.lastname: Tucker
authors.forename: S R
authors.initials: SR
authors.lastname: Heller
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007003:Hypoglycemia; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D014044:Tolbutamide
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005934:Glucagon; D014044:Tolbutamide; D004837:Epinephrine