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. 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.

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.

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.

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.

PLASMA INSULIN RESPONSE DURING ORAL GLUCOSE TOLERANCE TESTS IN NEWBORNS OF NORMAL AND GESTATIONAL DIABETIC MOTHERS

PEDIATRICS ◽  
1969 ◽  
Vol 44 (1) ◽  
pp. 76-83
Author(s):  
Rosita S. Pildes ◽  
Robert J. Hart ◽  
Richard Warrner ◽  
Marvin Cornblath
Keyword(s):  
Growth Hormone ◽  
Blood Glucose ◽  
Plasma Insulin ◽  
Insulin Response ◽  
Sampling Interval ◽  
Oral Glucose ◽  
Glucose Tolerance Tests ◽  
Fasting Plasma Insulin ◽  
Insulin Responses ◽  
Diabetic Mothers

The plasma insulin, growth hormone, free fatty acids (FFA), and blood glucose responses to the oral ingestion of glucose were studied in eight infants of gestational diabetic mothers (IGDM) and in 11 normal newborns during the first 24 hours of life. Fasting blood sugars and growth hormone values were similar in the IGDM and the normal. Fasting plasma insulin values were significantly higher (14 ± 2 µU/ml) in the IGDM than those in the normal (7 ± 1 µU/ml), and FFA values were significantly lower (1268 ± 42 µEq/l versus 1627 ± 155 µEq/l). Blood glucose values at each sampling interval after the ingestion of glucose were significantly lower in the IGDM than those in the normal. Plasma insulin responses were prompt in the IGDM and delayed in the normal newborns; corresponding values at 30 minutes were 30 ± 6 µU/ml in the IGDM and 15 ± 3 µU/ml in the normals.

AN ANALOGUE COMPUTER MODEL FOR THE INSULIN RESPONSE TO GLUCOSE INFUSION

1967 ◽  
Vol 55 (1) ◽  
pp. 163-183 ◽  
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

ABSTRACT 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.

ACUTE EFFECTS OF EXOGENOUS GROWTH HORMONE IN MAN: TIME- AND DOSE-BOUND MODIFICATION OF GLUCOSE TOLERANCE AND GLUCOSE-INDUCED INSULIN RELEASE

1975 ◽  
Vol 80 (2) ◽  
pp. 247-261 ◽  
Author(s):  
Ulf Adamson ◽  
Erol Cerasi
Keyword(s):  
Growth Hormone ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Insulin Release ◽  
Pancreatic Beta Cells ◽  
Chronic Administration ◽  
Major Influence ◽  
Insulinogenic Index ◽  
Significant Deterioration ◽  
K Value

ABSTRACT 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 μg 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 μg 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 μg 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 μg 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.

THE EFFECT OF THE PROGESTOGEN ETHYNODIOL DIACETATE ON GLUCOSE, INSULIN, AND GROWTH HORMONE AFTER SIX MONTHS TREATMENT

1972 ◽  
Vol 70 (2) ◽  
pp. 373-384 ◽  
Author(s):  
W. N. Spellacy ◽  
W. C. Buhi ◽  
S. A. Birk
Keyword(s):  
Growth Hormone ◽  
Blood Glucose ◽  
Plasma Insulin ◽  
Tolerance Test ◽  
Metabolic Effects ◽  
Oral Glucose ◽  
Hormone Levels ◽  
Glucose Levels ◽  
Ethynodiol Diacetate ◽  
Tolerance Curve

ABSTRACT Seventy-one women were treated with a daily dose of 0.25 mg of the progestogen ethynodiol diacetate. They were all tested with a three-hour oral glucose tolerance test before beginning the steroid and then again during the sixth month of use. Measurements were made of blood glucose and plasma insulin and growth hormone levels. There was a significant elevation of the blood glucose levels after steroid treatment as well as a deterioration in the tolerance curve in 12.9% of the women. The plasma insulin values were also elevated after drug treatment whereas the fasting ambulatory growth hormone levels did not significantly change. There was a significant association between the changes in glucose and insulin levels and the subject's age, control weight, or weight gain during treatment. The importance of considering the metabolic effects of the progestogen component of oral contraceptives is stressed.

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