POTENTIATION OF INSULIN RELEASE BY GLUCOSE IN MAN

1975 ◽  
Vol 79 (3) ◽  
pp. 511-534 ◽  
Author(s):  
Erol Cerasi
Keyword(s):  
Blood Glucose ◽  
Insulin Release ◽  
Dose Response ◽  
Pancreatic Beta Cell ◽  
Insulin Response ◽  
Initial Response ◽  
Normal Glucose Tolerance ◽  
Glucose Infusion ◽  
Clear Cut ◽  
The Right

ABSTRACT 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 potentiation 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 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. These studies indicate that the ability of glucose to initiate insulin release and its ability to generate time-bound potentiation in the islet correspond to two distinct functions. In the early stages of the diabetic syndrome, only the recognition of glucose as the initiator of an insulinogenic signal is impaired. The pancreatic beta-cell in these subjects seems to recognize normally glucose as the promotor of the potentiation.

EFFECT OF TWO SULPHONYLUREAS ON THE DOSE KINETICS OF GLUCOSE – INDUCED INSULIN RELEASE IN NORMAL AND DIABETIC SUBJECTS

1979 ◽  
Vol 91 (2) ◽  
pp. 282-293 ◽  
Author(s):  
Erol Cerasi ◽  
Suad Efendic ◽  
Christina Thornqvist ◽  
Rolf Luft
Keyword(s):  
Glucose Tolerance ◽  
Insulin Release ◽  
Dose Response ◽  
Insulin Dose ◽  
Insulin Response ◽  
Normal Glucose Tolerance ◽  
Response Curves ◽  
Normal Glucose ◽  
Slow Rise ◽  
The Right

The effect of two second generation sulphonylureas, gliquidone and glibenclamide, on insulin secretion has been studied in the basal state and in combination with glucose infusions in normal controls, patients with mild maturity-onset diabetes, and subjects with normal glucose tolerance but low insulin response. When injected intravenously, gliquidone caused rapid elevation of plasma insulin, peaking at 5 min in all groups, while glibenclamide induced a slow rise in insulin. Insulin response was somewhat smaller than normal in diabetics and low insulin responders. In all groups, 25 μg/kg glibenclamide and 200 μg/kg gliquidone were equipotent in generating an insulin response at the basal state. Equipotent amounts of sulphonylureas were combined with glucose infusions at three different dose levels. The glucose-insulin dose relationships, established by giving glucose alone, demonstrated curves that were flatter, and shifted to the right of the control in diabetics and low insulin responders, the changes being more marked in the former group. Addition of sulphonylurea induced a left shift in the dose-response relationships in controls and low insulin responders; under these conditions the effect of glibenclamide was more pronounced than that of gliquidone. The doseresponse relation for glucose-induced insulin release was completely normalized in low responders when sulphonylureas were added. In the group of mild diabetics, insulin response to glucose was enhanced by sulphonylureas only to a modest extent, the dose-response curves remaining grossly abnormal. It is concluded that, under acute experiments, sulphonylureas correct the deficient insulin response only in subjects with minimal abnormalities of the glucose tolerance; their effect in diabetics, even very mild ones, is marginal.

DIMINISHED SENSITIVITY OF THE INSULIN RESPONSE TO GLUCOSE FOLLOWING GROWTH HORMONE INFUSION IN MAN

1976 ◽  
Vol 81 (4) ◽  
pp. 735-742 ◽  
Author(s):  
Ulf Adamson ◽  
Erol Cerasi
Keyword(s):  
Growth Hormone ◽  
Blood Glucose ◽  
Insulin Release ◽  
Dose Response ◽  
Plasma Insulin ◽  
Insulin Dose ◽  
Insulin Response ◽  
Insulinogenic Index ◽  
K Value ◽  
Insulin Response To Glucose

ABSTRACT The acute effect of growth hormone (GH) administration on the dose-kinetics of glucose-stimulated insulin release was investigated in eight healthy, non-obese male subjects. The glucose-insulin dose-response relationship in these subjects was established by performing glucose infusions at three different dose levels. In a second series of experiments, the glucose infusions were preceded by a 30 min infusion of GH (40 μg/kg body weight), terminated 60 min before administration of glucose. GH induced small but significant reductions in the basal levels of blood glucose and plasma insulin. The glucose tolerance (k-value) was diminished after GH at all glucose doses. Both the initial late phases of insulin response to glucose were impaired following GH treatment. This effect was most pronounced when the intermediary glucose dose (eliciting a blood glucose level around 300 mg/100 ml) was used. Thus, the insulinogenic index (whole period of stimulation) was reduced by GH to 88.9 ± 7.6, 60.4 ± 7.1 and 74.3 ± 11.0% of the respective controls when the smallest, the intermediate, and the largest glucose loads, respectively, were given. The blood glucose-plasma insulin dose-response curves were shifted to the right of the control ones when glucose infusion was preceded by GH. These findings suggest that GH diminishes the sensitivity of the islet for the insulin releasing action of glucose. Some possible mechanisms by which GH may modify insulin release are discussed.

POTENTIATION OF INSULIN RELEASE BY GLUCOSE IN MAN

1975 ◽  
Vol 79 (3) ◽  
pp. 502-510 ◽  
Author(s):  
Erol Cerasi
Keyword(s):  
Glucose Metabolism ◽  
Adenylate Cyclase ◽  
Beta Cell ◽  
Insulin Release ◽  
Insulin Response ◽  
Glucose Infusion ◽  
Insulin Responses

ABSTRACT 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.

Alteration of islet neurotransmitter sensitivity following ventromedial hypothalamic lesion

1983 ◽  
Vol 244 (5) ◽  
pp. R635-R640 ◽  
Author(s):  
L. A. Campfield ◽  
F. J. Smith
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Dose Response ◽  
Response Curve ◽  
Pancreatic Beta Cell ◽  
Dose Response Curve ◽  
Norepinephrine Dose ◽  
Increased Sensitivity ◽  
The Right ◽  
Glucose Responsiveness

Recent studies suggest that alterations in autonomic neural activity may mediate the obese state observed following ventromedial hypothalamic (VMH) lesion. To assess the role of these alterations in the increased glucose responsiveness of the beta-cell observed in this state, we have determined the sensitivity of insulin secretion to norepinephrine or/and acetylcholine in statically incubated pancreatic islets from rats 30-40 days after VMH lesion. In islets from VMH-lesioned rats compared with islets from sham-operated and intact rats, the acetylcholine dose-response curve was shifted down and to the right, indicating a decreased sensitivity, whereas the norepinephrine dose-response curve was translated to the left, indicating an increased sensitivity. The interaction profile, which summarizes combined neurotransmitter exposure on insulin secretion, was shifted in the direction of net inhibition. Thus it was concluded that, following VMH lesion, autonomic neurotransmitter sensitivity of the pancreatic beta-cell was altered. It is suggested that these alterations play a role in the adaptation of the beta-cell to the experimentally induced obese state.

scholarly journals Glucose Tolerance and Insulin Release in Malnourished Rats

1976 ◽  
Vol 50 (3) ◽  
pp. 153-163 ◽  
Author(s):  
C. Weinkove ◽  
E. A. Weinkove ◽  
B. L. Pimstone
Keyword(s):  
Blood Glucose ◽  
Glucose Tolerance ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Plasma Insulin ◽  
Blood Glucose Concentration ◽  
Protein Energy Malnutrition ◽  
Insulin Response ◽  
Intravenous Glucose ◽  
Protein Energy

1. Young Wistar rats were used as an experimental model to determine the effects of protein-energy malnutrition on glucose tolerance and insulin release. 2. Malnourished rats presented some of the features commonly found in human protein-energy malnutrition, such as failure to gain weight, hypoalbuminaemia, fatty infiltration of the liver and intolerance of oral and intravenous glucose loads. 3. The rate of disappearance of glucose from the gut lumen was greater in the malnourished rats but there was no significant difference in portal blood glucose concentration between normal and malnourished rats 5 and 10 min after an oral glucose load. 4. Insulin resistance was not thought to be the cause of the glucose intolerance in the malnourished animals since these rats had a low fasting plasma insulin concentration with a normal fasting blood glucose concentration and no impairment in their hypoglycaemic response to exogenous insulin administration. Furthermore, fasting malnourished rats were unable to correct the insulin-induced hypoglycaemia despite high concentrations of hepatic glycogen. 5. Malnourished rats had lower peak plasma insulin concentrations than normal control animals after provocation with oral and intravenous glucose, intravenous tolbutamide and intravenous glucose plus aminophyllin. This was not due to a reduction in the insulin content of the pancreas or potassium deficiency. Healthy weanling rats, like the older malnourished rats, had a diminished insulin response to intravenous glucose and intravenous tolbutamide. However, their insulin response to stimulation with intravenous glucose plus aminophyllin far exceeded that of the malnourished rats. Thus the impairment of insulin release demonstrated in the malnourished rats cannot be ascribed to a ‘functional immaturity’ of the pancreas.

ON THE ACTION OF TOLBUTAMIDE IN NORMAL MAN

1973 ◽  
Vol 72 (3) ◽  
pp. 506-518 ◽  
Author(s):  
A. Widström ◽  
E. Cerasi
Keyword(s):  
Blood Glucose ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Blood Glucose Concentration ◽  
Insulin Response ◽  
Blocking Agent ◽  
Significant Inhibition ◽  
Normal Man ◽  
Adrenergic Blocking ◽  
Plasma Insulin Response

ABSTRACT The plasma insulin response to intravenously administered tolbutamide was measured in healthy subjects under experimentally induced variations in the blood glucose concentration. Decreasing blood glucose concentration down to 51 and 25% of the basal level by the iv administration of 0.05 and 0.10 IU of insulin/kg body weight, respectively, resulted in significant inhibition of the insulin response to tolbutamide. The degree of inhibition was correlated to the extent of the hypoglycaemia. This inhibition seems to be only partially mediated by catecholamines, since blocking the α-adrenergic receptors with phentolamine could not restore the action of tolbutamide. Furthermore, whereas the prevention of the hypoglycaemia that normally follows tolbutamide administration resulted in an enhancement of the insulin response to the drug, phentolamine had no such effect. These results indicate that the decrease in blood glucose concentration as such, rather than activation of the adrenergic mechanisms, is responsible for the inhibition of tolbutamide-induced insulin release. Hence, the blood glucose level at the time of tolbutamide administration seems to determine the insulin response to the drug. The administration of the β-adrenergic blocking agent propranolol, in doses known to suppress glucose-induced insulin release in man, had no effect on the insulin response to tolbutamide. Our studies thus do not confirm the reports of other investigators that sulphonylureas may act on the islet cell as β-adrenergic agonists.

An analogue computer model for the insulin response to glucose infusion

SIMULATION ◽  
1971 ◽  
Vol 16 (6) ◽  
pp. 243-255 ◽  
Author(s):  
Erol Cerasi ◽  
Bertil Andersson
Keyword(s):  
Blood Glucose ◽  
Glucose Uptake ◽  
Computer Model ◽  
Plasma Insulin ◽  
Insulin Response ◽  
Quantitative Information ◽  
Glucose Infusion ◽  
Analogue Computer ◽  
Dynamic Factors ◽  
Insulin Response To Glucose

An analogue computer model has been constructed for the analysis of the interrelationship between blood glucose and plasma insulin concentrations during glucose infusion. The model presented gives quantitative information on the effect of plasma insulin on glucose uptake, the total amount of glucose taken up by the tissues at a given time, the effect of blood glucose on the release of stored and newly formed insulin, and the rapidity by which plasma insulin is increased in response to hyperglycaemia. Such an analogue computer model might be a useful tool in the investigation of the various dynamic factors involved in the glucose- insulin interrelationship.

POTENTIATION OF INSULIN RELEASE BY GLUCOSE IN MAN

1975 ◽  
Vol 79 (3) ◽  
pp. 483-501 ◽  
Author(s):  
Erol Cerasi
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Insulin Dose ◽  
Late Phase ◽  
Insulin Response ◽  
Glucose Infusion ◽  
Dose Response Curve ◽  
Maximum Effect ◽  
Releasing Effect ◽  
Effect Of Glucose

ABSTRACT 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. The dose-dependency of this potentiation was investigated by keeping the second glucose challenge at a constant level and altering the dose of the first infusion. It was necessary to reach hyperglycaemias around and above 300 mg/100 ml during the first infusion in order to obtain enhancement of the insulin response to the second stimulus. The dose-response curve of the potentiating effect of glucose is thus displayed towards the right when compared with that describing the insulin releasing effect of glucose, which has its threshold around 100 mg/100 ml. It is suggested that glucose exerts a dual effect on the pancreatic islets: an immediate one which initiates the release of insulin, and a time-bound one which modulates the first action.

STUDIES ON THE PATHOGENESIS OF DIABETES IN ACROMEGALY

1967 ◽  
Vol 56 (4) ◽  
pp. 593-607 ◽  
Author(s):  
Rolf Luft ◽  
Erol Cerasi ◽  
Carl Axel Hamberger
Keyword(s):  
Glucose Tolerance ◽  
Insulin Response ◽  
Normal Glucose Tolerance ◽  
Glucose Infusion ◽  
Intravenous Glucose ◽  
Highly Active ◽  
Normal Glucose ◽  
Insulin Response To Glucose ◽  
Active Acromegaly ◽  
Plasma Insulin Response

ABSTRACT Plasma insulin response to glucose infusion was found to be markedly increased in 20 patients with active acromegaly and with normal intravenous glucose tolerance. The insulin response was more pronounced in patients with highly active acromegaly than in those showing moderately active disease. In five patients with active acromegaly and with decreased glucose tolerance the insulin response was delayed and smaller than normal, i. e. similar to that seen in diabetic subjects without acromegaly. After successful treatment of the acromegaly insulin response to glucose infusion was normalized in the patients with normal glucose tolerance. In those with decreased glucose tolerance the diabetic type of insulin response remained unchanged even when the glucose tolerance was normalized. It is suggested that diabetes in connection with acromegaly develops only in prediabetic individuals, i.e. subjects with decreased insulin response to hyperglycaemia, who are unable to overcome the diabetogenic effect of growth hormone by compensatory hyperinsulinism.

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