A NEW PRINCIPLE FOR THE COMPARISON OF INSULIN SECRETORY RESPONSES

1973 ◽  
Vol 74 (3) ◽  
pp. 511-523 ◽  
Author(s):  
Klaus Johansen

ABSTRACT A new principle for the comparison of insulin secretory response has been devised. It consists in the selection of groups of subjects with identical glucose tolerance when subjected to the same amount of oral and intravenous glucose and of intravenous tolbutamide. In this way the problems and assumptions inherent in the use of the insulin/glucose ratio and the administration of different amount of insulin secretagogues have been avoided. Using this new method of comparison of insulin secretory responses it has been demonstrated that young people maintain the same blood glucose level after stimulation with much smaller plasma insulin levels than their older counterparts, i. e. young non-diabetic and diabetic subjects seem to be more 'sensitive' to endogenous insulin than the old, alternately the old subjects are more 'resistant' to endogenous insulin than young subjects.

1973 ◽  
Vol 74 (3) ◽  
pp. 524-541 ◽  
Author(s):  
Klaus Johansen

ABSTRACT In an attempt to circumvent the difficulties inherent in the use of insulin/glucose ratios a new principle for the comparison of insulin secretory resonses has been developed. From large groups of obese and non-obese people subjects are selected so that the subgroups ultimately formed are comparable with regard to age and to their degree of glucose tolerance. This means that the blood glucose curves of the two groups are merging and that the beta cells are subjected to identical glycaemic stimuli. The study shows that obese young non-diabetics and obese young and old diabetics exhibit an augmented insulin response to stimulation with oral and intravenous glucose and to intravenous tolbutamide. No increase in plasma insulin secretory response is, however, demonstrable in obese, old non-diabetics.


Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Varunkumar G Pandey ◽  
Lars Bellner ◽  
Victor Garcia ◽  
Joseph Schragenheim ◽  
Andrew Cohen ◽  
...  

20-HETE (20-Hydroxyeicosatetraenoic acid) is a cytochrome P450 ω-hydroxylase metabolite of arachidonic acid that promotes endothelial dysfunction, microvascular remodeling and hypertension. Previous studies have shown that urinary 20-HETE levels correlate with BMI and plasma insulin levels. However, there is no direct evidence for the role of 20-HETE in the regulation of glucose metabolism, obesity and type 2 diabetes mellitus. In this study we examined the effect of 20-SOLA (2,5,8,11,14,17-hexaoxanonadecan-19-yl-20-hydroxyeicosa-6(Z),15(Z)-dienoate), a water-soluble 20-HETE antagonist, on blood pressure, weight gain and blood glucose in Cyp4a14 knockout (Cyp4a14-/-) mice fed high-fat diet (HFD). The Cyp4a14-/- male mice exhibit high vascular 20-HETE levels and display 20-HETE-dependent hypertension. There was no difference in weight gain and fasting blood glucose between Cyp4a14-/- and wild type (WT) on regular chow. When subjected to HFD for 15 weeks, a significant increase in weight was observed in Cyp4a14-/- as compared to WT mice (56.5±3.45 vs. 30.2±0.7g, p<0.05). Administration of 20-SOLA (10mg/kg/day in drinking water) significantly attenuated the weight gain (28.7±1.47g, p<0.05) and normalized blood pressure in Cyp4a14-/- mice on HFD (116±0.3 vs. 172.7±4.6mmHg, p<0.05). HFD fed Cyp4a14-/- mice exhibited hyperglycemia as opposed to normal glucose levels in WT on a HFD (154±1.9 vs. 96.3±3.0 mg/dL, p<0.05). 20-SOLA prevented the HFD-induced hyperglycemia in Cyp4a14-/- mice (91±8mg/dL, p<0.05). Plasma insulin levels were markedly high in Cyp4a14-/- mice vs. WT on HFD (2.66±0.7 vs. 0.58±0.18ng/mL, p<0.05); corrected by the treatment with 20-SOLA (0.69±0.09 ng/mL, p<0.05). Importantly, glucose and insulin tolerance tests showed impaired glucose homeostasis and insulin resistance in Cyp4a14-/- mice on HFD; ameliorated by treatment with 20-SOLA. This novel finding that blockade of 20-HETE actions by 20-SOLA prevents HFD-induced obesity and restores glucose homeostasis in Cyp4a14-/- mice suggests that 20-HETE contributes to obesity, hyperglycemia and insulin resistance in HFD induced metabolic disorder. The molecular mechanisms underlying 20-HETE mediated metabolic dysfunction are being currently explored.


1983 ◽  
Vol 245 (6) ◽  
pp. E575-E581 ◽  
Author(s):  
A. L. Vallerand ◽  
J. Lupien ◽  
L. J. Bukowiecki

The metabolic interactions of cold exposure, cold acclimation, and starvation on glucose tolerance and plasma insulin levels were studied in precannulated, unrestrained, and unanesthetized rats. Cold exposure (48 h at 5 degrees C) significantly reduced the insulin response to intravenous glucose injection (P less than 0.01) while improving glucose tolerance (P less than 0.01). Starvation (48 h at 25 degrees C) also reduced the insulin response (P less than 0.01) but did not significantly alter glucose tolerance. “Accelerated starvation” induced by starving rats for 48 h at 5 degrees C dramatically reduced both basal and glucose-stimulated insulin levels while even improving glucose tolerance, resulting in a 15-fold reduction in the insulinogenic index. Cold acclimation (3 wk at 5 degrees C) induced essentially the same alterations as cold exposure. Approximately reversed changes were observed when cold-acclimated rats were returned to a warm environment for 15–18 h. Results from these studies indicate that 1) cold exposure and starvation, but not cold acclimation, act synergistically in decreasing the sensitivity and/or the capacity of pancreatic islets for secreting insulin in response to glucose stimulation; 2) glucose tolerance and possibly insulin sensitivity of peripheral tissues are enhanced by cold exposure and starvation, although glucose tolerance is improved by cold exposure only, not by starvation; 3) an improved glucose tolerance with barely detectable plasma insulin levels was obtained in cold-starved rats under normal physiological conditions.


1976 ◽  
Vol 50 (3) ◽  
pp. 153-163 ◽  
Author(s):  
C. Weinkove ◽  
E. A. Weinkove ◽  
B. L. Pimstone

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.


1991 ◽  
Vol 66 (3) ◽  
pp. 363-379 ◽  
Author(s):  
Peter R. Ellis ◽  
Fathy M. Dawoud ◽  
Edwin R. Morris

The effectiveness of guar gum in reducing post-prandial blood glucose and plasma insulin levels in human subjects seems to depend mainly on its ability to increase the viscosity of digesta in the small intestine. However, the precise relationship between the rheological properties of guar gum (either in vitro or in vivo) and the changes in blood metabolites and hormones is unknown. The aim of the present study, therefore, was to investigate the effects of wheat breads containing guar gum samples varying in molecular weight (Mw) and particle size (characteristics that strongly influence the rheological properties of guar gum) on post-prandial blood glucose and plasma insulin levels in healthy subjects. The sensory qualities of breads containing guar-gum flours of different Mw were also evaluated using a hedonic scoring technique. No significant differences in the post-prandial blood glucose responses were found between the control and guar breads. However, all the guar breads elicited significant (P < 0.05) decreases in the post-prandial rise in plasma insulin, an effect that did not appear to be influenced by large variations in Mw or particle size of guar gum. Moreover, the sensory qualities of guar bread were markedly improved by using low Mw grades of guar gum.


1982 ◽  
Vol 95 (1) ◽  
pp. 125-135
Author(s):  
L. V. Beck ◽  
Ilora Basu ◽  
Sally L. Hegeman

Anti-insulin serum (AIS) injected intravenously into adult male mice was allowed to complex endogenous plasma insulin for a fixed time before blood samples were taken. In each plasma sample, insulin was separated from antibody using acid alcohol and the free insulin was estimated by radioimmunoassay. We consider AIS to be most useful for the estimations of in-vivo insulin secretion rates over the period 0·5–5 min after its injection. The lower limit is governed by the time required for mixing and complexing of endogenous insulin. The use of a short upper limit is because antibody complexed with antigen leaves plasma more rapidly than does free antibody, carrying antigen with it. Increases in insulin per ml plasma were appreciably greater in mice injected with glucose or l-arginine plus AIS than in mice injected with glucose or l-arginine only. Hence more realistic values for in-vivo insulin secretion rates may be obtained by the use of AIS to retain most insulin in plasma than by estimations of plasma insulin levels.


Diabetologia ◽  
1974 ◽  
Vol 10 (6) ◽  
pp. 725-730 ◽  
Author(s):  
M. Hautecouverture ◽  
G. Slama ◽  
R. Assan ◽  
G. Tchobroutsky

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