Somatostatin regulation of beta-cell function in the normal human fetuses and in neonates with persistent hyperinsulinemic hypoglycemia.
To investigate the insulin-inhibitory effects of somatostatin during fetal development, and the defective regulation of insulin release in persistent hyperinsulinemic hypoglycemia of infancy (PHHI), we made perifusion experiments with islet-like cell clusters obtained from 14 human fetal pancreases (HFP) before 20 weeks of gestation and 6 neonates pancreatectomized because of PHHI (5 cases of diffuse and 1 adenomatous islet cell hyperplasia). Somatostatin-14 (600 nmol/L) suppressed insulin release only marginally (20% and 25% suppression in 2 and 20 mmol/L glucose, respectively) in HFP, whereas supplementation of the perifusate with 14 nmol/L glucagon potentiated the suppression to 57%. Somatostatin-28 (600 nmol/L) caused a 35% inhibition in insulin release from the HFP. In static incubation of HFP, somatostatin-14 caused a weak dose-dependent inhibition of insulin release, but had no effect on (pro)insulin biosynthesis. In the PHHI infants, somatostatin infusion suppressed hyperinsulinemia effectively before pancreatectomy. In vitro, 600 nmol/L somatostatin-14 suppressed insulin release clearly better than in the HFP experiments (35-61% inhibition). Glucose (20 mmol/L) induced a 2- to 3-fold increase in insulin release in two clinically mild cases of PHHI, but no response at all in the four others. We conclude that human fetal beta-cells are relatively insensitive to somatostatin, possibly because of low cellular cAMP levels. Furthermore, insulin release from PHHI cells is poorly stimulated by glucose but effectively blocked by somatostatin, supporting the concept of somatostatin deficiency in PHHI.
Otonkoski
T
T
Children's Hospital, University of Helsinki, Finland.
Andersson
S
S
Simell
O
O
D000028:Abortion, Induced; D005260:Female; D005333:Fetus; D005865:Gestational Age; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology* / Q000601:surgery; D007003:Hypoglycemia / Q000209:etiology*; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D010180:Pancreatectomy; D011247:Pregnancy; D011384:Proinsulin / Q000096:biosynthesis; D013004:Somatostatin / Q000494:pharmacology*
D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; D011384:Proinsulin; D005947:Glucose