Insulin secretion in fetal and newborn sheep.

1978 ◽  
Vol 235 (5) ◽  
pp. E467 ◽  
Author(s):  
A F Philipps ◽  
B S Carson ◽  
G Meschia ◽  
F C Battaglia

The relationships between arterial plasma insulin, glucose, and fructose concentrations during the fed and fasted state were studied in seven fetal lambs and their mothers. A significant correlation between insulin and glucose concentration was noted in all fetal lambs and in their mothers. Fetal sensitivity to glucose, as measured by the slopes of the insulin-response curves, was equal to that of the adult although the fetal response was shifted to the left of the maternal. Glucose infusion in four fetal lambs caused significant insulin elevations but no early insulin response (phase I). Maternal fasting caused no alteration in glucose-induced response in the fetus. Similar glucose infusions in newborn and 1-mo-old lambs demonstrated significant early-phase insulin secretion. Basal insulin to glucose ratios were consistent with an adult pattern as early as 3 days after birth.

1992 ◽  
Vol 263 (4) ◽  
pp. R782-R784
Author(s):  
H. Karmann ◽  
N. Rideau ◽  
T. Zorn ◽  
A. Malan ◽  
Y. Le Maho

Plasma glucose and insulin levels were measured in chronically catheterized, freely moving, undisturbed geese, which were offered a free standard meal after an overnight fast. The insulin level markedly rose within the first minute after the start of food ingestion, whereas plasma glucose did not increase. This early insulin response was not correlated with the size of the meal. In contrast, both postabsorptive insulin response and plasma glucose changes were dependent on meal size. When a small amount of food (2-6 g) was eaten, insulin returned to basal level within 30 min, whereas plasma glucose remained unchanged. Larger meals (15-20 g) maintained plasma insulin at a higher level and induced a sustained rise of plasma glucose. These results indicate that there is a cephalic phase of insulin secretion at the beginning of the meal in birds as previously described in mammals.


1981 ◽  
Vol 50 (1) ◽  
pp. 71-77 ◽  
Author(s):  
A. Wirth ◽  
C. Diehm ◽  
H. Mayer ◽  
H. Morl ◽  
I. Vogel ◽  
...  

Plasma insulin and C-peptide were simultaneously determined under various conditions in 11 endurance-trained athletes and 12 nonathletes. Both groups performed an exhaustive ergometer test and an endurance test with 38% of the maximal achieved work load for 45 min. An intravenous glucose tolerance test was also performed. In the basal state, athletes had low plasma insulin and C-peptide concentrations. During exercise, insulin and C-peptide decreased similarly in both groups. In the recovery period, insulin and C-peptide rose within a few minutes. There were differences between the extent as well as the time course of this "rebound" effect after exhaustive or endurance exercise that might be related to glucose alterations. The insulin response but not the C-peptide response after glucose injection was blunted in trained subjects. Results indicate that basal plasma insulin concentrations are lower in athletes due to reduced insulin secretion. During exercise, insulin secretion is diminished independent of the training state. The blunted response of insulin after glucose administration in athletes is due to an enhanced plasma clearance.


1981 ◽  
Vol 98 (1) ◽  
pp. 81-86 ◽  
Author(s):  
Ralph A. DeFronzo ◽  
Christian Binder ◽  
John Wahren ◽  
Philip Felig ◽  
Eleuterio Ferrannini ◽  
...  

Abstract. The ability of insulin to inhibit its own secretion was examined in 15 normal subjects given an intravenous infusion of insulin in a dose of 0.25, 0.50, 1.0, 5.0 or 10.0 mU/kg/min for two hours. Arterial plasma insulin concentration achieved during the infusion segregated into three levels of hyperinsulinaemia: 35 ± 1 (mean ± sem), 87 ± 15 and 828 ± 210 μU/ml. Plasma glucose concentration was kept constant at the basal level by a variable glucose infusion. Fasting C-peptide (0.29 ± 0.02 pmol/ml) fell significantly in all subjects during hyperinsulinaemia and reached a concentration of 0.19 ± 0.03 pmol/ml at 60 min and 0.14 ± 0.03 at 120 min after the start of the insulin infusion. The C-peptide response was not related to the infusion dose nor to the steady state plasma insulin concentration. It is concluded that (a) basal insulin secretion as evaluated from C-peptide measurements is inhibited by small (24 ± 3 μU/ml) physiological elevations in plasma insulin concentration independent of changes in plasma glucose, and (b) supraphysiological or even pharmacological elevations in plasma insulin do not result in a further decrease in endogenous insulin secretion above that achieved with mild hyperinsulinaemia.


1971 ◽  
Vol 50 (1) ◽  
pp. 59-74 ◽  
Author(s):  
J. M. BASSETT ◽  
G. D. THORBURN

SUMMARY Foetal lambs (100–150 days' gestation) with indwelling vascular catheters were used to study the regulation of the insulin concentration in the plasma of foetal lambs in utero. Immediately after the implantation of the catheters the insulin concentration in foetal plasma was significantly correlated with the foetal glucose and fructose concentrations and with the maternal glucose concentration. On the next day the foetal insulin concentration was significantly correlated only with the maternal glucose concentration. Both glucose and fructose, when infused i.v., increased the insulin concentration in foetal plasma, but the increases were slow and far less than those observed in newborn lambs infused with glucose or fructose. Intravenous infusion of isoprenaline or glucagon did not alter the plasma insulin concentration of foetal lambs, but both caused a rapid increase in the insulin concentration of newborn lambs. Glucagon did not potentiate the insulin response to glucose. Addition of aminophylline to a glucagon infusion failed to cause insulin secretion in foetal lambs. The results suggest the cyclic-3′,5′-AMP dependent part of the insulin secretory mechanism does not develop fully before the last week of gestation. Gel filtration of foetal plasma on Sephadex indicated that the immunoreactive material present was insulin. No significant amounts of proinsulin were found.


2004 ◽  
Vol 287 (3) ◽  
pp. E371-E385 ◽  
Author(s):  
Andrea Caumo ◽  
Livio Luzi

To fulfill its preeminent function of regulating glucose metabolism, insulin secretion must not only be quantitatively appropriate but also have qualitative, dynamic properties that optimize insulin action on target tissues. This review focuses on the importance of the first-phase insulin secretion to glucose metabolism and attempts to illustrate the relationships between the first-phase insulin response to an intravenous glucose challenge and the early insulin response following glucose ingestion. A clear-cut first phase occurs only when the β-cell is exposed to a rapidly changing glucose stimulus, like the one induced by a brisk intravenous glucose administration. In contrast, peripheral insulin concentration following glucose ingestion does not bear any clear sign of biphasic shape. Coupling data from the literature with the results of a β-cell model simulation, a close relationship between the first-phase insulin response to intravenous glucose and the early insulin response to glucose ingestion emerges. It appears that the same ability of the β-cell to produce a pronounced first phase in response to an intravenous glucose challenge can generate a rapidly increasing early phase in response to the blood glucose profile following glucose ingestion. This early insulin response to glucose is enhanced by the concomitant action of incretins and neural responses to nutrient ingestion. Thus, under physiological circumstances, the key feature of the early insulin response seems to be the ability to generate a rapidly increasing insulin profile. This notion is corroborated by recent experimental evidence that the early insulin response, when assessed at the portal level with a frequent sampling, displays a pulsatile nature. Thus, even though the classical first phase does not exist under physiological conditions, the oscillatory behavior identified at the portal level does serve the purpose of rapidly exposing the liver to elevated insulin levels that, also in virtue of their up-and-down pattern, are particularly effective in restraining hepatic glucose production.


2008 ◽  
pp. 935-945
Author(s):  
M Orečná ◽  
R Hafko ◽  
Z Bačová ◽  
J Podskočová ◽  
D Chorvát ◽  
...  

Objective of this study was to characterize osmotically-induced insulin secretion in two tumor cell lines. We compared response of freshly isolated rat pancreatic islets and INS-1 and INS-1E tumor cell lines to high glucose, 30 % hypotonic medium and 20 % hypertonic medium. In Ca(2+)-containing medium glucose induced insulin release in all three cell types. Hypotonicity induced insulin secretion from islets and INS-1 cells but not from INS-1E cells, in which secretion was inhibited despite similar increase in cell volume in both cell types. GdCl(3) (100 micromol/l) did not affect insulin response from INS-1E cells to hypotonic challenge. Hypertonic medium inhibited glucose-induced insulin secretion from islets but not from tumor cells. Noradrenaline (1 micromol/l) inhibited glucose-induced but not swelling-induced insulin secretion from INS-1 cells. Surprisingly, perifusion with Ca(2+)-depleted medium showed distinct secretory response of INS-1E cells to hypotonicity while that of INS-1 cells was partially inhibited. Functioning glucose-induced insulin secretion is not sufficient prerequisite for hypotonicity-induced response in INS-1E cells suggesting that swelling-induced exocytosis is not essential step in the mechanism mediating glucose-induced insulin secretion. Both cell lines are resistant to inhibitory effect of hyperosmolarity on glucose-induced insulin secretion. Response of INS-1E cells to hypotonicity is inhibited by the presence of Ca(2+) in medium.


1990 ◽  
Vol 259 (2) ◽  
pp. E155-E161 ◽  
Author(s):  
D. S. King ◽  
M. A. Staten ◽  
W. M. Kohrt ◽  
G. P. Dalsky ◽  
D. Elahi ◽  
...  

Insulin secretion in response to glucose stimulation is reduced in endurance-trained humans. In this study, a modified hyperglycemic clamp, with a superimposed arginine infusion and fat meal, was performed on eight endurance-trained and nine untrained men to determine whether insulin secretory capacity is reduced by exercise training. Raising the plasma glucose concentration to approximately 450 mg/dl resulted in a plasma insulin response in the trained men that was approximately 64% lower than that of the untrained (peak values: 54 +/- 8 vs. 149 +/- 35 microU/ml; P less than 0.001). When a primed continuous infusion of arginine was superimposed on the hyperglycemia, the plasma insulin response was also markedly lower (66%) in the trained subjects, reaching peak values of 333 +/- 68 and 974 +/- 188 microU/ml for trained and untrained subjects, respectively (P less than 0.005). When insulin secretion was further stimulated during the arginine-infused hyperglycemia by the ingestion of a high-fat meal, peak insulin concentrations averaged 989 +/- 205 microU/ml in the trained compared with 2,232 +/- 455 microU/ml in the untrained subjects (P less than 0.01). The response of gastric inhibitory polypeptide (GIP) to the fat meal was delayed and blunted, suggesting that some enteric factor(s) other than GIP mediated the insulinotropic effect of the fat meal. The reduced plasma insulin response in trained people to the stimuli investigated suggests that regular exercise produces either several adaptations within the beta-cell or a single alteration of the beta-cell that results in an attenuation of the insulin secretory response to glucose, arginine, and fat ingestion.


1980 ◽  
Vol 238 (4) ◽  
pp. E336-E340 ◽  
Author(s):  
H. R. Berthoud ◽  
E. R. Trimble ◽  
E. G. Siegel ◽  
D. A. Bereiter ◽  
B. Jeanrenaud

The ability of saccharin, in comparison with glucose and tap water, to elicit glycemia-independent neurally mediated insulin secretion was investigated in chronically catheterized, freely moving rats. Plasma glucose and insulin concentrations were measured continuously from venous blood with a sampling resolution of one per minute. In normal rats, 1 ml of 0.15% saccharin caused a significant rapid rise in peripheral plasma insulin levels lasting up to 5 min, without significant changes in glycemia. Tap water alone also induced a transient elevation in insulinemia but was much smaller than the saccharin-induced response. In streptozotocin diabetic rats bearing intrahepatic, presumably denervated islet isografts, these rapid insulin responses to oral saccharin and tap water stimulation were completely abolished, whereas the early insulin response to intravenous glucose was decreased by only about 30%. These results are consistent with the concept of gustatory and other oral sensory signals acting as triggers for neurally mediated insulin release.


1984 ◽  
Vol 64 (5) ◽  
pp. 269-270 ◽  
Author(s):  
Y. SASAKI ◽  
H. HIRATSUKA ◽  
M. ISHIDA

Cold exposure markedly suppressed the increase in insulin secretion in response to feeding in sheep, while environmental temperature had no significant effect on basal levels of plasma insulin before feeding. Key words: Sheep, insulin, feeding, cold


2014 ◽  
Vol 99 (10) ◽  
pp. 3774-3781 ◽  
Author(s):  
Ralph A. DeFronzo ◽  
Devjit Tripathy ◽  
Muhammad Abdul-Ghani ◽  
Nicolas Musi ◽  
Amalia Gastaldelli

Abstract Aims and Hypothesis: The insulin secretion/insulin resistance (IR) (disposition) index (ΔI/ΔG ÷ IR, where Δ is change from baseline, I is insulin, and G is glucose) is commonly used as a measure of β-cell function. This relationship is curvilinear and becomes linear when log transformed. ΔI is determined by 2 variables: insulin secretion rate (ISR) and metabolic clearance of insulin. We postulated that the characteristic curvilinear relationship would be lost if Δ plasma C-peptide (ΔCP) (instead of Δ plasma insulin) was plotted against insulin sensitivity. Methods: A total of 441 individuals with impaired glucose tolerance (IGT) from ACT NOW received an oral glucose tolerance test and were randomized to pioglitazone or placebo for 2.4 years. Results: Pioglitazone reduced IGT conversion to diabetes by 72% (P < .0001). ΔI/ΔG vs the Matsuda index of insulin sensitivity showed the characteristic curvilinear relationship. However, when ΔCP/ΔG or ΔISR/ΔG was plotted against the Matsuda index, the curvilinear relationship was completely lost. This discordance was explained by 2 distinct physiologic effects that altered plasma insulin response in opposite directions: 1) increased ISR and 2) augmented metabolic clearance of insulin. The net result was a decline in the plasma insulin response to hyperglycemia during the oral glucose tolerance test. These findings demonstrate a physiologic control mechanism wherein the increase in ISR ensures adequate insulin delivery into the portal circulation to suppress hepatic glucose production while delivering a reduced but sufficient amount of insulin to peripheral tissues to maintain the pioglitazone-mediated improvement in insulin sensitivity without excessive hyperinsulinemia. Conclusions: These results demonstrate the validity of the disposition index when relating the plasma insulin response to insulin sensitivity but underscore the pitfall of this index when drawing conclusions about β-cell function, because insulin secretion declined despite an increase in the plasma insulin response.


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