Development of the insulin secretion mechanism in fetal and neonatal rat pancreatic B-cells: response to glucose, K+, theophylline, and carbamylcholine

Abstract

We studied the development of the insulin secretion mechanism in the pancreas of fetal (19-and 21-day-old), neonatal (3-day-old), and adult (90-day-old) rats in response to stimulation with 8.3 or 16.7 mM glucose, 30 mM K + , 5 mM theophylline (Theo) and 200 µM carbamylcholine (Cch). No effect of glucose or high K + was observed on the pancreas from 19-day-old fetuses, whereas Theo and Cch significantly increased insulin secretion at this age (82 and 127% above basal levels, respectively). High K + also failed to alter the insulin secretion in the pancreas from 21-day-old fetuses, whereas 8.3 mM and 16.7 mM glucose significantly stimulated insulin release by 41 and 54% above basal levels, respectively. Similar results were obtained with Theo and Cch. A more marked effect of glucose on insulin secretion was observed in the pancreas of 3-day-old rats, reaching 84 and 179% above basal levels with 8.3 mM and 16.7 mM glucose, respectively. At this age, both Theo and Cch increased insulin secretion to close to twotimes basal levels. In islets from adult rats, 8.3 mM and 16.7 mM glucose, Theo, and Cch increased the insulin release by 104, 193, 318 and 396% above basal levels, respectively. These data indicate that pancreatic B-cells from 19-day-old fetuses were already sensitive to stimuli that use either cAMP or IP 3 and DAG as second messengers, but insensitive to stimuli such as glucose and high K + that induce membrane depolarization. The greater effect of glucose on insulin secretion during the neonatal period indicates that this period is crucial for the maturation of the glucose-sensing mechanism in B-cells.

Effect of thawing rate and post-thaw culture on the cryopreserved fetal rat islets: Functional and morphological correlation

“…The late response of the fetal islets to 30 mmol/l glucose and the improper response to the final challenge with theophylline could be attributed to the immaturity of the fetal islets, as it was noticed in the control islets as well as in the slow and fast thawed islets. Similar findings were also reported in the literature and were attributed to the immaturity of the B-cells (Dudek et al, 1984;Hegre et al, 1984;Mourmeaux et al, 1985;Masaki et al, 1987;Tuch and Zheng, 1993;Bergsten et al, 1998;Mendonca et al, 1998). However, the underlying mechanism is not exactly known.…”

Physiological development of insulin secretion, calcium channels, and GLUT2 expression of pancreatic rat β-cells

“…Glucose homeostasis during fetal development in mammals is mainly achieved by the mother, because fetal pancreatic ␤-cells barely respond to high glucose concentrations by increasing insulin secretion (21,26). In this stage, insulin secretion is scarce and monophasic, similar to the pattern that is observed in the onset of type 2 diabetes (9,48,49).…”

Beta cell coupling and connexin expression change during the functional maturation of rat pancreatic islets

“…It has long been known that this glucose responsiveness is normally established in the few days that follow birth, even though beta cells are already equipped in the late prenatal period with most of their adult features [3][4][5][6][7][8]. Several events occurring during the early neonatal period, including changes in K + membrane permeability, production of GLUT2, protein kinase C-alpha, Ca 2+ channels and key enzymes of the NADH shuttles, are implicated in the maturation of beta cell function [1,2,[4][5][6][7][8][23][24][25]. We now show that gap junction/CX36 signalling, which contributes significantly to the proper function of adult beta cells [17, Fig.…”

“…When compared with adult islets, fetal and neonatal islets from different species exhibit a reduced secretory response to glucose and other secretagogues [1][2][3][4][5][6][7][8]. The nature of this poor responsiveness is not fully understood, and has been variably attributed to many factors, including fuel metabolites, intracellular signals, hormones and other environmental conditions [1][2][3][8][9][10][11].…”