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Biomedical subjects

E Cerasi

Publications and source records attributed to E Cerasi.

At least 145 records · Page 8Linked to original sources
PubMed1975

Defective early phase insulin release in perifused isolated pancreatic islets of spiny mice (Acomys cahirinus).

In order to characterize pancreatic beta cell function in Geneva bred spiny mice (acomys cahirinus), the dynamics of immunoreactive insulin release were examined during perifusion of pancreatic islets isolated from normoglycemic acomys. The initial insulin response of acomys was slow: no clear-cut early (1 to 10 min) peak of insulin release was observed when glucose in the perifusion medium was abruptly raised from 2.8 mM to concentrations as high as 56 mM. This was true for islets of either young, or older more obese acomys. However, after 20 to 30 min of perifusion at the high glucose concentrations, the rate of insulin release from acomysislets became similar to that from islets of rats or mice. By contrast, glucose-induced insulin release responses observed with islets of Wistar-derived rats, Swiss albino mice, and inbred C57BL/6J lean or obese (ob/ob) mice, were clearly biphasic. Tolbutamide 1.5 mM, arginine 16 mM, and theophylline 10 mM were ineffective in stimulating insulin release from acomys islets in the presence of a substimulatory glucose concentration (2.8 mM), whereas these agents were effective in rat islets at the same substimulatory concentration of glucose. On the other hand, when these agents, as well as cyclic AMP 10 mM or cytochalasin B 10 mug/ml were applied in the presence of a stimulating concentration of glucose (16.8 mM), the glucose-stimulated insulin release from acomys islets was increased to the same or to a greater extent than from rat islets. It is suggested that the failure of all the agents tested to stimulate an early rapid phase of insulin release from acomys islets may be secondary to the observed initial insensitivity to glucose, which insensitivity may in turn reflect a selective impairment in the recognition of glucose as an insulinogenic signal in this species.

Age Factors↗
PubMed1975

Glucose tolerance in newborn infants of healthy mothers: its relationship to the mothers' insulin response to glucose infusion.

It has earlier been postulated that a low insulin response to a glucose infusion is characteristic for the prediabetic individual (Cerasi & Luft 1967c). There is also evidence that some infants of individuals with low insulin response might have a carbohydrate metabolism that is in some respects similar to that of newborn infants to diabetic mothers (Edström et al. 1974). In the present study 15 infants to low insulin responders (ILR) and 22 infants to high insulin responders (IHR) were subjected to an intravenous glucose load (IVGTT) at 2-24 h age. A significant difference in glucose tolerance was found between the groups, the mean k-value for the ILR being 1.39 plus or minus 0.41 and that for the IHR 1.05 plus or minus 0.09 (P smaller than 0.05). No mothers were found to have a gestational diabetes (with the possible exception of one low insulin responders) but during late pregnancy the mean k-value at IVGTT in the low responders decreased from non-pregnant values (the mean difference being 0.41 plus or minus 0.20, P smaller 0.025) while the high responders did not show a corresponding decrease (mean difference 0.12 plus or minus 0.25, P greater than 0.05). No other differences between the groups of infants that could influence the k-value could be found apart from the mothers being low or high insulin responders. Our findings show that a low insulin response in the mothers might effect the glucose tolerance of the foetus even in the absence of continuous maternal hyperglycaemia in late pregnancy.

Birth Weight↗
PubMed1975

Acute suppressive effect of human growth hormone on basal insulin secretion in man.

The acute effects of human growth hormone (GH) on the basal levels of glucose and insulin in blood were investigated in 11 healthy men. GH doses of 5, 10, 20, and 40 mug/kg body weight were given iv as a constant-rate infusion over 30 min, and resulted in peak hormone levels (30 min) of 20.5 plus or minus 1.0, 48.5 plus or minus 2.2, 108.2 plus or minus 4.5, and 229.2 plus or minus 14.6 ng/ml, respectively. There was a small (max 9.8 plus or minus 2.6%) but significant decrease in the blood glucose level, observed already at 15 min after the beginning of the GH infusion and persisting up to 90 min. The highest dose of GH induced the most marked changes, but there was otherwise no clear correlation between dose and effect. The basal plasma insulin levels showed a more marked (max 16.0 plus or minus 4.7%) decrease which was not correlated, in time or in magnitude, with the changes in blood glucose. In some subjects, in whom no significant decrease in blood glucose was observed, plasma insulin still demonstrated a similar fall (max 20.2 plus or minus 7.6%). Neither were these changes in plasma insulin correlated to the dose of GH within the range used in this study. The findings suggested that the early, insulin-like effect of GH on blood glucose is distinct from its effect on the pancreas. The latter is a suppressive one, consistent with earlier findings on glucose-induced insulin release.

Adult↗
PubMed1975

Potentiation of insulin release by glucose in man.

Glucose-induced potentiation of glucose-induced insulin release was quantitatively evaluated in 14 non-obese subjects with normal glucose tolerance but decreased insulin response, and in six non-obese patients with mild, adult-onset diabetes, by measuring the insulin responses to two consecutive glucose infusion tests, administered with 40 or 70 min interval. Enhancement of the second insulin response occurred in both groups. In low insulin responders, the dose-response relationship between blood glucose and plasma insulin was flatter and shifted to the right when compared to the control. Pretreatment with glucose increased strikingly the slope of this relationship, the responses now being within the normal range. The enhancement induced by glucose seems to be of multiplicative type. In mildly diabetic subjects, insulin response to glucose infusion was low and sluggish, only a minor initial response being observed. Pretreatment with glucose modified the profile of the insulin response, a clear-cut initial response of greater magnitude being obtained at least in some of the patients. The sensitivity of the islet to the potentiating action of glucose was higher in low insulin responders than in controls, the minimal glucose concentration needed to induce potentiations of the forthcoming response being much lower. The dose-response curve for the relationship between the blood glucose level of the preinfusion period and the percentual enhancement of the insulin response obtained at the second stimulation was, in low insulin response obtained at the second stimulation was, in low insulin responders, higher than and shifted to the left of the curve of the control subjects. In the group of diabetics, sensitivity for potentiation by glucose seemed not different from the controls.

Adult↗
PubMed1975

Acute effects of exogenous growth hormone in man: time- and dose-bound modification of glucose tolerance and glucose-induced insulin release.

The time and dose dependency of the effects of a 30-min long iv infusion of human growth hormone (GH) on glucose tolerance and glucose-stimulated insulin release was investigated in 19 healthy subjects. Glucose tolerance deteriorated immediately following GH, and the k-value continued to decrease up to 300 min later. A small but significant reduction of glucose tolerance persisted 24 h after GH administration. Significant deterioration of glucose tolerance was observed with the smallest GH dose used (5 mug per kg body weight), increasing the amount of the hormone having no further major influence. Glucose-stimulated insulin release was significantly inhibited 1 h after administration of a relatively high GH dose (40 mug per kg), both if expressed as mean plasma insulin levels, or as insulin release per magnitude of glucose stimulation (insulinogenic index). In the majority of subjects, insulin release was inhibited also by lower GH doses (5-20 mug GH per kg). However, the mean change with these doses was not statistically significant. The inhibitory effect of GH on insulin secretion seemed to have a duration of several hours. Five hours, but not 24 h, after GH administration (10 mug GH per kg) insulin release was still significantly suppressed. It is suggested that the initial effect of GH on pancreatic beta cells may be inhibition of insulin release, in contrast with the enhancement of insulin secretion observed during chronic administration of GH.

Adolescent↗
PubMed1975

Insulin secretion in the spiny mouse (Acomys cahirinus). Dose and time kinetic studies with glucose in vivo and in vitro.

Plasma insulin responses to the intravenous injection of glucose in the doses of 0.5, 1.5, and 3.0 gm./kg. were compared in spiny mice (Acomys cahirinus) and weight-matched Swiss albino mice. The mean early (two-minute) plasma insulin response was significantly lower in Acomys at all doses of glucose injected; whereas, at later times (5, 15, and 30 minutes), differences in plasma insulin concentrations in the two species of mice were smaller or nonexistent. Plasma glucose clearance was significantly less in the Acomys. In terms of glucose dose kinetics, there was a decreased capacity of the mean plasma insulin response in Acomys compared with albino mice at two minutes; whereas, at later times, the mean dose response curve for Acomys was shifted to the right of that for albino mice, indicating a decreased sensitivity to glucose in the Acomys. There was, however, a large variation between the plasma insulin responses of the eight individual Acomys mice tested. There was a significant correlation in individual Acomys between the plasma insulin response, expressed as an insulinogenic index, integrated over the thirty minutes after injection of glucose 3.0 gm./kg. in vivo, and the insulin released from pancreatic islets obtained from the corresponding Acomys and perifused for thirty minutes with glucose 1,000 mg./100 ml. in vitro (r = 0.77, p less than 0.05). It is concluded that the rate and magnitude of the insulin response to glucose in an individual Acomys reflects mainly the degree of sensitivity to glucose of the pancreatic beta cells in that animal.

Animals↗
PubMed1975

Decreased cyclic AMP and insulin response to glucose in isolated islets of neonatal rats.

The (3H) cyclic AMP accumulation was measured in incubations of pancreatic islets from one-day, six-day, and thirty-five-day-old rats exposed to a low (0.6 mg./ml.) or a high (3.0 mg./ml.) glucose concentration with or without the addition of 0.1 mM. of the phosphodiesterase inhibitor 3-isobutyl- 1 -methylxanthine (IBMX). In the thirty-five-day-old rats, (3H) cyclic AMP accumulation was significantly enhanced after sixty minutes' incubation in a high glucose concentration and further increased by IBMX. These changes were paralleled by a stimulated insulin release, measured simultaneously. By contrast, in the one-day-old rats, no effect of glucose with or without IBMX was seen on (3H) cyclic AMP, while the minor insulin release due to high glucose alone was markedly potentiated by IBMX. Even in the presence of this agent the insulin response to glucose was, however, clearly inferior to that seen in the thirty-five-day-old animals. The stimulatory patterns of glucose-induced insulin release in the six-day-old animals was intermediate between the other two age groups. At this age, stimulation of (3H) cyclic AMP due to glucose was observed only in the presence of IBMX. Measurement of (3H) cyclic AMP after three minutes' incubation confirmed these different stimulatory patterns of glucose in the age groups studied. It is suggested that the inefficiency of glucose to stimulate the adenyl cyclase-cyclic AMP system of the beta cell from fetal and neonatal animals may be one important factor determining the insensitivity to the insulin-releasing action of glucose that exists at this stage of development.

Adenylyl Cyclases↗
PubMed1975

Patterns of free fatty acids, glycerol, D-beta-hydroxybutyrate and insulin in pregnant women and their newborn infants. Effects of a low and a high insulin response to glucose in the mothers.

Twenty-eight healthy women, 17 with high and 11 with low insulin response to glucose but with normal glucose tolerance, were followed throughout pregnancy. Plasma FFA, glycerol and D-beta-hydroxybutyrate as well as plasma insulin and glucose in blood were determined before and during a glucose infusion test (GIT) in each trimester and after pregnancy. In 13 infants of high insulin responders (IHR) and 10 infants of low responders (ILR) an intravenous glucose tolerance test (IVGTT) was performed, and the above lipid parameters were studied at birth and during the IVGTT. The low responder group was postulated to consist mainly of prediabetic individuals (8). Their infants have previously been shown to have an increased glucose assimilation rate at IVGTT (12, 13), as has been shown for infants of diabetic mothers. There was little difference between the two groups of mothers except for the insulin levels during the GIT in non-pregnant and early pregnant subjects, which were considerably lower in the low responders. They all had decreased fasting levels of FFA, glycerol, and D-beta-hydroxybutyrate in mid-pregnancy and normal values in late pregnancy. The ILR showed the same changes in FFA and glycerol as the IHR, but their D-beta-hydroxybutyrate levels were higher at birth than those of the IHR and lower after birth. Another difference found, was the correlation between birth weight and fasting insulin (and to some extent the insulin level at birth) in the ILR group, which was not found in the IHR. Apart from those differences the ILR and the IHR seemed to handle their fat metabolism in a similar way in the early neonatal perinatal period.

Adult↗
PubMed1975

Potentiation of insulin release by glucose in man. I. Quantitative analysis of the enhancement of glucose-induced insulin secretion by pretreatment with glucose in normal subjects.

The effect of repeating a 60 min glucose infusion at a 40 to 70 min interval was investigated after an overnight fast in 14 healthy, non-obese subjects with normal glucose tolerance and normal insulin response to glucose administration. When a hyperglycaemic plateau of around 300 mg/100 ml was induced by the first glucose infusion, the insulin response to a second challenge was enhanced over the range of stimulations used. Both the early and late phase insulin responses were amplified, the enhancement being more marked with higher stimulatory levels of glucose. The blood glucose-insulin dose-response curve became steeper after pretreatment with glucose, the stimulatory threshold level not being altered. These findings suggest that the synergism between the glucose pretreatment, and the insulin releasing effect of glucose, is of multiplicative type, resulting in increase of the maximum effect of the glucose.

Adult↗
PubMed1975

Potentiation of insulin release by glucose in man. II. Role of the insulin response, and enhancement of stimuli other than glucose.

If two consecutive glucose infusions are administered with 40 min of rest between, the insulin response to the second challenge is markedly potentiated. When the insulin response to the first glucose infusion was suppressed by 65% with the aid of adrenaline, potentiation of the insulin response to the second infusion was not modified. This suggests that the generation of a state of enhancement in the islet does not necessitate that glucose exerts its insulin releasing action. It is postulated that islet glucose metabolism may be involved in producing the potentiation. Pretreatment of the subjects with a glucose infusion enhanced also the insulin responses to glucagon and to tolbutamide, given intravenously 50 min later. Thus, the potentiation generated by glucose is not restricted to the insulinogenic signal induced by glucose. The eventual role that the beta-cell adenylate cyclase may play in this respect is discussed.

Adult↗
PubMed1975

Acute suppressive effect of human growth hormone on insulin release induced by glucagon and tolbutamide in man.

The acute effect of human growth hormone on glucagon--and tolbutamide--induced insulin release was investigated in 14 non-obese subjects with normal glucose tolerance. Sixty mn after an i.v. growth hormone infusion of 40 mug/kg per kg body weight, the insulin response to glucagon (10 subjects) as well as to tolbutamide (6 subjects) was significantly suppressed by about 35%, both if the insulin secretion was expressed as change in peak response (p less than 0.05 for both insulinogogues) or as per cent change of the integrated insulin area over 30 minutes (p less than 0.005 and p less than 0.05, respectively). A lesser reduction of glucagon-induced insulin secretion was observed also after smaller doses of growth hormone (10 and 20 mug/kg). The reduction of the insulin response was associated with a significantly smaller blood glucose fall following the glucagon and tolbutamide administration. These results support the hypothesis that growth hormone in vivo has an acute suppressive effect on insulin secretion, and show that this action is not limited to glucose-induced stimulation of the islets.

Acromegaly↗
PubMed1975

Feed-back inhibition of insulin secretion in subjects with high and low insulin response to glucose.

The plasma insulin response to two successive stimulations by glucose was measured in 12 healthy subjects, 5 of whom demonstrated subnormal insulin responses to glucose infusion (low insulin responders). 15 g of glucose were injected rapidly i.v. at 0 and 20 min, and blood glucose and plasma insulin levels determined at intervals of 2-10 min. In both groups, the peak elevation of plasma insulin, and the peak insulinogenic index, were significantly inhibited at the second stimulation. The degree of inhibition was smaller in subjects with low insulin response. The integrated insulin response and the integrated insulinogenic index during the 20 min following glucose administration were also significantly inhibited at the second glucose challenge in subjects with low insulin responders. The degree of inhibition of the second insulin response (20-40 min) shows significant correlation with the insulinogenic index of the first response (0-20 min) in the total material. It is suggested that this inhibition of insulin release on repeating the stimulus, (a) may offer an explanation sustained stimulation by glucose; (b) is probably generated by the phenomenon of insulin secretion, and (c) might thus represent a negative feed-back loop in insulin secretion. (d) Decreased insulin secretion in low responders is not due to the presence of increased inhibition.

Adult↗