Development of the biphasic response to glucose in fetal and neonatal rat pancreas.
A study on the development of biphasic insulin release and sensitivity to inhibitors has been performed using perifused rat pancreas at 19.5 days of gestation (3 days before birth) and at 3 days after birth. In the fetal pancreas, 16.7 mM glucose caused a marked stimulation of insulin release that did not, however, manifest a biphasic response and was not inhibited by verapamil, a Ca2+ channel blocker. This suggested that the immature response was due to either a lack of voltage-dependent Ca2+ channels or their failure to open in response to glucose. Depolarizing concentrations of KCl stimulated insulin release, which was inhibited by verapamil, demonstrating that functional Ca2+ channels were present. In the presence of 16.7 mM glucose, quinine, which blocks glucose-sensitive k+ channels, potentiated the response of the fetal pancreas that now became sensitive to verapamil, demonstrating that functional K+ channels were also present in the fetal pancreatic beta-cell. The immaturity of the response is not due specifically to a defect in glucose metabolism; rather the metabolism of nutrient secretagogues fails to couple with the K+ channel in the fetal islet and thus fails to depolarize the beta-cell membrane. Three days after birth the pattern of response to high glucose is biphasic. Insulin release in fetal pancreas was inhibited by epinephrine and somatostatin.
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D004837:Epinephrine / Q000494:pharmacology; D005333:Fetus / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007329:Insulin Antagonists / Q000494:pharmacology; D000078790:Insulin Secretion; D007651:Keto Acids / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology
D007328:Insulin; D007329:Insulin Antagonists; D007651:Keto Acids; D013004:Somatostatin; D011189:Potassium Chloride; C013082:alpha-ketoisocaproic acid; D011803:Quinine; D005947:Glucose; D004837:Epinephrine