Kazuyuki Sasaki

Insulinotropic action of human glicentin in dogs

Glicentin has been demonstrated to be released in response to the intraluminal administration of nutrients, but its biological action remains unknown. To clarify the effect of glicentin on the endocrine function of the pancreas, the present study was performed using an in vivo local circulation system of the canine pancreas. During infusion of 0.5% solution of glucose or arginine, 100 and 400 pmol glicentin and 400 pmol glucagon were administered into the pancreaticoduodenal artery (PA) within 10 minutes at 40-minute intervals successively. During glucose infusion, blood glucose in the femoral artery did not change following administration of 100 pmol glicentin, but slightly increased following 400 pmol glicentin. Plasma insulin (immunoreactive insulin [IRI]) in the pancreaticoduodenal vein (PV) increased significantly only following infusion of 400 pmol glicentin. Plasma glucagon (immunoreactive glucagon [IRG]), measured with a specific antiserum to the C-terminal portion of glucagon, did not change following administration of 100 pmol glicentin, but was slightly elevated following 400 pmol glicentin. Plasma total IRG, measured with a nonspecific antiserum, increased promptly after administration of 100 and 400 pmol glicentin. During arginine infusion, the response of plasma IRI to glicentin was markedly exaggerated both in dosages of 100 and 400 pmol. From the present study it was concluded that human glicentin clearly increases insulin release from the canine pancreas.

Plasma glicentin in diabetic and gastrectomized patients

Recent successful synthesis of human glicentin prompted us to establish an immunoassay method for determination of human glicentin in plasma. Human glicentin in plasma was measured using a newly developed sandwich ELISA. The mean fasting levels of human glicentin were 18.6+/-2.4 and 19.7+/-2.1 pM in normal subjects and diabetic patients, respectively. In diabetic patients with renal failure, plasma glicentin was elevated, exceeding 100 pM. In normal subjects, plasma glicentin increased to a peak level of about 130 pM at 60 min after an oral glucose load, and then decreased. In patients who underwent gastrectomy, plasma glicentin rapidly increased to a peak of about 300 pM at 30 min after oral glucose load. In a patient with short bowel syndrome plasma glicentin did not change following an oral glucose load. These results correspond with previous findings for gut glucagon-like immunoreactive materials (GLI) or enteroglucagon. We conclude that glicentin is secreted from the small intestine in response to intraluminal glucose stimulation in humans.