Fasting for 24 hours inhibits glucose-induced insulin secretion from isolated rat pancreatic islets. At glucose 15 raM the inhibition is only present during the initial 30-45 minutes of stimulation. It decreases at higher glucose concentrations and disappears at glucose 37.5 mM. In islets of fed rats, 15 minutes of stimulation with glucose 15 mM induced an almost threefold rise of islet cyclic adenosine 3',5'-monophosphate (cAMP). Both this effect and the secretory response were inhibited by about 65 per cent after 24 hours of fasting and almost completely by 72 hours of food deprivation. Fasting for 24 hours also caused a 56 per cent inhibition of the rise of islet cAMP and insulin secretion induced by D-glyceraldehyde 10 mM, but the inhibition was not further enhanced by 72 hours of fasting. Fasting for 24 and 72 hours did not significantly inhibit the islet cAMP response to 15 minutes of stimulation with glucose 37.5 mM. Fasting for 24 hours impaired neither islet glucose oxidation (14CO2 production) nor over-all glucose utilization (production of 3H-water from [5-3H] glucose) during the initial 30 minutes of stimulation with glucose. After 72 hours of fasting, both over-all glucose utilization and glucose oxidation were reduced by 25 per cent. These findings suggest that inhibition of the islet cAMP response is a primary factor in the early (24 hours) fasting-induced impairment of the insulin secretory response to glucose stimulation at 5-15 mM. Inhibition of islet glucose metabolism seems to be an independent additional phenomenon that becomes manifest after longer periods of food deprivation.

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In intact rats 16 h of fasting reduced the plasma insulin response to i.v. stimulation with either glucose, tolbutamide or glibenelamide by 50--80 %, without affecting the extractable insulin content of the pantreas. In subsequent studies with the isolated perfused rat panereas two distinct patterns of insulin release could be discerned during the secondary phase. In the fed state, glucose 1.5 mg/ml induced a more or less constant elevation of the insulin secretion rate over 30 rain (type I). At glucose concentrations of 2 and 3 mg/ml the release pattern was characterized by progressively increasing secretion rates (type II pattern). Infusion of tolbutamide (0.2 mg/ml) lowered the threshold for glueose stimulation and induced both patterns of secretion at lower glucose concentrations. Fasting for 24~ h caused a 70--80 % in-hibition of insulin secretion per 30 rain a~ glucose levels of 1.5 and. 2 mg/ml. Decreased glucose sensitivity was indicated by a shift to the right of the entire dose-response curve for glucose and by reduced inhibition (30 %) at a glucose level of 3 mg/ml. The effect of tolbutamide was also strongly diminished. The percent inhibition of the response to tolbutamide at different levels of glucose showed a pattern of inhibition similar to that observed with glucose alone. These findings suggest that the glucose-dependent release mechanism is highly sensitive to relatively short periods of fasting.

The influence of breast or formula feeding together with that of a single supplementation of vitamin K1 at birth, on the vitamin K1 level and vitamin K-dependent clotting factors were studied in 65 breast and 15 formula fed infants. All breast fed newborns without supplementation (n = 25) had very low serum vitamin K1 at weeks 1 and 6. Oral vitamin K supplementation (n = 22) or i.m. (n = 18) at birth resulted in high serum levels at week 1, while at week 6 the effect had disappeared. Formula fed infants had vitamin K1 values within the normal adult range at all study points. The low serum levels of vitamin K1 were not associated with haemorrhagic disorders or coagulation abnormalities. The mean values of vitamin K1 in maternal sera at weeks 1 and 6 were 2.3 nmol/l and 1.8 nmol/l and in breast milk 2.7 nmol/l and 2.0 nmol/l respectively. No correlation existed between the values in breast milk and maternal serum. To maintain serum levels of vitamin K1 within the adult physiological range, repeated administration of low doses is needed in breast fed newborns beyond 1 week of age.

Pancreatic islet development and insulin storage were studied in foetal rats during the last 4 days of gestation (day 19 to 22 post-coitum (p. c.)) and in 1 and 5 days old neonatal rats. Adult female virgin rats were also studied. The percentage of granulated B-cells per islet, the degree of B-cell granulation and the islet insulin concentration rose from low levels on day 19 to adult levels on day 22 and remained stable after birth. This indicates that the qualitative maturation of the pancreatic islets as insulin producing units is completed on the last day of gestation. The percentage of islet tissue slowly rose from 0.7 % at day 19 to 1.5 % on day 22. A further and much more rapid rise occurred during the first day of birth. At the 5th postnatal day the islets comprised 3.6 % of the pancreas versus 1.1% in adult rats. Likewise, the neonatal pancreatic insulin concentration was about 3 times higher than in the adult pancreas.The foetal pancreas as a whole showed rapid exponential growth between day 18 and 21 p. c., but a sudden decline in growth rate occurred from day 21 onward. The total mass of islet tissue, on the other hand, continued to expand at its high initial rate up to the first day after birth, whereafter this high rate also declined. The high concentration of insulin in the neonatal rat pancreas therefore appears to be due to differential growth rates of the endocrine and exocrine tissue during the last day of pregnancy and the first day after birth. Pregnancy in the rat lasts for 22-22Vs days. Embryonic islet-like structures appear in the pancreatic diverticulum around the 15th day of gestation and their size and number rapidly increase in the subsequent days (Hard 1944).