ENHANCEMENT OF INSULIN RELEASE TO ACUTE GLYCAEMIC STIMULATION WITH DEPRESSION OF BASAL INSULIN PRODUCTION RATES IN INSULINOMA FOLLOWING DIAZOXIDE ADMINISTRATION

1970 ◽  
Vol 63 (3) ◽  
pp. 392-404 ◽  
Author(s):  
Richard E. Bailey ◽  
Albert Castro ◽  
Rosanne M. Kramer ◽  
Dorothy Macfarlane

ABSTRACT Single and double load oral glucose tolerance tests were performed repetitively both before and during administration of diazoxide to a 15-year old girl who had an insulin secreting islet cell tumour. Plasma insulin concentrations increased above baseline values by a greater magnitude in response to a single acute oral glycaemic stimulus following diazoxide treatment, compared to the increases resulting from comparable prediazoxide glucose tolerance tests, and plasma insulin either attained higher values or sustained elevations for a longer duration during the early part (first hour) of the single load tests. This provides evidence that diazoxide does not prevent the normal insulin release response to a glycaemic stimulus, and that enhanced insulin secretion rates may occur with insulinomas under the study conditions employed. Fasting plasma insulin concentrations were lower during the period of diazoxide administration which indicates that insulin biosynthesis was depressed under fasting steady-state conditions. Considering that the first part of the glucose tolerance curve reflects primarily insulin release, our data is consistent with the view that insulin storage within the insulinoma cells is preserved under the study conditions employed and may even be enhanced by diazoxide. Consequently, depression of insulin biosynthesis is considered to be a resultant effect and not a primary action of diazoxide. These results suggest a possible basis for »distinguishing« types of insulinomas should additional perspective reveal that glycaemic-induced enhancement of insulin secretion rates cannot be made to occur uniformly in diazoxide treated patients having insulinomas.

1980 ◽  
Vol 94 (2) ◽  
pp. 196-200 ◽  
Author(s):  
O. Gedik ◽  
S. Akalin ◽  
Zehra Koray

Abstract. Insulin secretion in response to an oral glucose challenge during acute hypercalcaemia was studied. Oral glucose tolerance tests (OGTT) were performed in 12 non-diabetic, non-obese human volunteers, aged 20–28 years. Blood samples were collected for calcium, glucose and insulin determination. The next day the same volunteers received a 4 h infusion of calcium gluconate (15 mg/kg/4 h) and were administered glucose 1 h after starting the infusion. Serum calcium, glucose and insulin concentrations were measured again. Infusion of calcium gluconate resulted in an increase in serum calcium concentration of 5 mg/100 ml over 4 h. During these infusions no significant changes in glucose concentrations were noted. On the other hand, the total mean insulin concentration, expressed as the area under the 3 h glucose tolerance curve, and the insulin peak at 30 min were significantly increased during hypercalcaemia (P < 0.001). These data indicate that acute hypercalcaemia does not affect carbohydrate tolerance but increases insulin secretion in human beings.


1983 ◽  
Vol 102 (4) ◽  
pp. 549-556 ◽  
Author(s):  
K. Berntorp ◽  
E. Trell ◽  
J. Thorell ◽  
B. Hood

Abstract. In a material of 3596 oral glucose tolerance tests (OGTT) performed in a population investigation of middle-aged males in Malmö, fasting and 120 min values of blood glucose and plasma insulin immunoreactivity (IRI) were studied while taking factors like body weight, smoking, alcohol, gastric resection and selfreported diabetes heredity into account. The fasting as well as the 120 min levels of both glucose and IRI were markedly influenced by body weight and smoking habits but not by the hereditary background. At 120 min, but not in the fasting state, there was a linear correlation between the IRI and glucose levels. The increase of IRI on glucose was significantly steeper in most of the hereditary subjects in comparison with their non-hereditary controls.


1996 ◽  
Vol 148 (3) ◽  
pp. 391-398 ◽  
Author(s):  
S C Blair ◽  
I D Caterson ◽  
G J Cooney

Abstract The effect of adrenalectomy (ADX) on glucose tolerance and insulin secretion was examined in conscious mice made obese by a single injection of gold thioglucose (GTG). To facilitate such a study a chronic jugular catheter was implanted into the mice at the time of performing the ADX or sham-ADX. One week after ADX, the body weight (GTG-obese+sham-ADX, 35·6 ± 0·6 g; GTG-obese+ADX, 33·1 ± 0·6 g; P<0·05) and glycogen content of the liver (GTG-obese+sham-ADX, 2·4 ± 0·2 μmol/liver; GTG-obese+ADX, 1·6 ± 0·1 μmol/liver; P<0·05) of GTG-injected mice were reduced. Plasma glucose concentrations, in both the overnight fasted state and in response to an intravenous glucose load were also reduced following ADX of GTG-obese mice, but not to the level of the sham-ADX control mice. However, ADX completely normalized plasma insulin concentrations in both the basal state and also in response to a glucose load, as indicated by the finding that the integrated insulin secretory response of the ADX GTG-obese mice was not different from that of sham-ADX control mice (control+sham-ADX, 192 ± 5 min.μU/ml; GTG-obese+ADX, 196 ± 10 min.μU/ml). The effects of ADX on carbohydrate metabolism were not restricted to GTG-injected mice, as ADX of control mice decreased fasting plasma glucose levels and reduced liver glycogen and plasma insulin concentrations. The normalization of insulin release in ADX GTG-obese mice occurred while these mice were still obese and glucose intolerant. This suggests that the decreased insulin release was not due solely to an ADX-induced improvement in insulin sensitivity and/or weight loss. Removal of central glucocorticoid effects on the parasympathetic stimulation of insulin release may play a role in the reduced insulin release observed after ADX of obese and control mice, although peripheral effects of glucocorticoid deficiency on glycogen synthesis in the liver may also influence whole animal glucose homeostasis. Journal of Endocrinology (1996) 148, 391–398


2008 ◽  
Vol 93 (7) ◽  
pp. 2633-2638 ◽  
Author(s):  
G. Nijpels ◽  
W. Boorsma ◽  
J. M. Dekker ◽  
F. Hoeksema ◽  
P. J. Kostense ◽  
...  

Abstract Context: In persons with impaired glucose tolerance (IGT), both impaired insulin secretion and insulin resistance contribute to the conversion to type 2 diabetes mellitus (T2DM). However, few studies have used criterion standard measures to asses the predictive value of impaired insulin secretion and insulin resistance for the conversion to T2DM in a Caucasian IGT population. Objectives: The objective of the study was to determine the predictive value of measures of insulin secretion and insulin resistance derived from a hyperglycemic clamp, including the disposition index, for the development of T2DM in a Caucasian IGT population. Design, Setting, and Participants: The population-based Hoorn IGT study consisted of 101 Dutch IGT subjects (aged &lt; 75 yr), with mean 2-h plasma glucose values, of two separate oral glucose tolerance tests, between 8.6 and 11.1 mmol/liter. A hyperglycemic clamp at baseline was performed to assess first-phase and second-phase insulin secretion and insulin sensitivity. During follow-up, conversion to T2DM was assessed by means of 6-monthly fasting glucose levels and yearly oral glucose tolerance tests. Results: The cumulative incidence of T2DM was 34.7%. Hazard ratio for T2DM development adjusted for age, sex, and body mass index was 5.74 [95% confidence interval (CI) 2.60–12.67] for absence of first insulin peak, 1.58 (95% CI 0.60–4.17) for lowest vs. highest tertile of insulin sensitivity, and 1.78 (95% CI 0.65–4.88) for lowest vs. highest tertile of the disposition index. Conclusions: In these Caucasian persons with IGT, the absence of the first insulin peak was the strongest predictor of T2DM.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Faradianna E. Lokman ◽  
Harvest F. Gu ◽  
Wan Nazaimoon Wan Mohamud ◽  
Mashitah M. Yusoff ◽  
Keh Leong Chia ◽  
...  

Aims. To evaluate the antidiabetic properties of borapetol B known as compound 1 (C1) isolated fromTinospora crispain normoglycemic control Wistar (W) and spontaneously type 2 diabetic Goto-Kakizaki (GK) rats.Methods. The effect of C1 on blood glucose and plasma insulin was assessed by an oral glucose tolerance test. The effect of C1 on insulin secretion was assessed by batch incubation and perifusion experiments using isolated pancreatic islets.Results. An acute oral administration of C1 improved blood glucose levels in treated versus placebo groups with areas under glucose curves 0–120 min being72±17versus344±10 mmol/L (P<0.001) and492±63versus862±55 mmol/L (P<0.01) in W and GK rats, respectively. Plasma insulin levels were increased by 2-fold in treated W and GK rats versus placebo group at 30 min (P<0.05). C1 dose-dependently increased insulin secretion from W and GK isolated islets at 3.3 mM and 16.7 mM glucose. The perifusions of isolated islets indicated that C1 did not cause leakage of insulin by damaging islet beta cells (P<0.001).Conclusion. This study provides evidence that borapetol B (C1) has antidiabetic properties mainly due to its stimulation of insulin release.


1976 ◽  
Vol 83 (4) ◽  
pp. 772-780 ◽  
Author(s):  
J. R. Henderson ◽  
D. B. Jefferys ◽  
R. H. Jones ◽  
D. Stanley

ABSTRACT Oral and intravenous glucose tolerance tests were performed on normal fasting subjects, with and without atropine. Insulin release after oral glucose was significantly diminished by atropine, and this effect could not be ascribed to the drug delaying glucose absorption. However, insulin release brought about by intravenous glucose was not altered by atropine. Possible interpretations of these results are discussed.


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