Insulin reciprocally regulates glucagon secretion in humans.
OBJECTIVE
We tested the hypothesis that an increase in insulin per se, i.e., in the absence of zinc, suppresses glucagon secretion during euglycemia and that a decrease in insulin per se stimulates glucagon secretion during hypoglycemia in humans.


METHODS
We measured plasma glucagon concentrations in patients with type 1 diabetes infused with the zinc-free insulin glulisine on three occasions. Glulisine was infused with clamped euglycemia (∼95 mg/dl [5.3 mmol/l]) from 0 to 60 min on all three occasions. Then, glulisine was discontinued with clamped euglycemia or with clamped hypoglycemia (∼55 mg/dl [3.0 mmol/l]) or continued with clamped hypoglycemia from 60 to 180 min.


RESULTS
Plasma glucagon concentrations were suppressed by -13 ± 3, -9 ± 3, and -12 ± 2 pg/ml (-3.7 ± 0.9, -2.6 ± 0.9, and -3.4 ± 0.6 pmol/l), respectively, (all P < 0.01) during zinc-free hyperinsulinemic euglycemia over the first 60 min. Glucagon levels remained suppressed following a decrease in zinc-free insulin with euglycemia (-14 ± 3 pg/ml [-4.0 ± 0.9 pmol/l]) and during sustained hyperinsulinemia with hypoglycemia (-14 ± 2 pg/ml [-4.0 ± 0.6 pmol/l]) but increased to -3 ± 3 pg/ml (-0.9 ± 0.9 pmol/l) (P < 0.01) following a decrease in zinc-free insulin with hypoglycemia over the next 120 min.


CONCLUSIONS
These data indicate that an increase in insulin per se suppresses glucagon secretion and a decrease in insulin per se, in concert with a low glucose concentration, stimulates glucagon secretion. Thus, they document that insulin is a β-cell secretory product that, in concert with glucose and among other signals, reciprocally regulates α-cell glucagon secretion in humans.
Cooperberg
Benjamin A
BA
Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, Missouri, USA.
Cryer
Philip E
PE
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D005934:Glucagon / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D055815:Young Adult
D005934:Glucagon; D006442:Glycated Hemoglobin; D007328:Insulin
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