Sensitivity of insulin secretion to feedback inhibition by hyperinsulinaemia

1981 ◽  
Vol 98 (1) ◽  
pp. 81-86 ◽  
Author(s):  
Ralph A. DeFronzo ◽  
Christian Binder ◽  
John Wahren ◽  
Philip Felig ◽  
Eleuterio Ferrannini ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Feedback Inhibition ◽  
Normal Subjects ◽  
Insulin Concentration ◽  
Plasma Insulin Concentration ◽  
C Peptide ◽  
Endogenous Insulin ◽  
Arterial Plasma

Abstract. The ability of insulin to inhibit its own secretion was examined in 15 normal subjects given an intravenous infusion of insulin in a dose of 0.25, 0.50, 1.0, 5.0 or 10.0 mU/kg/min for two hours. Arterial plasma insulin concentration achieved during the infusion segregated into three levels of hyperinsulinaemia: 35 ± 1 (mean ± sem), 87 ± 15 and 828 ± 210 μU/ml. Plasma glucose concentration was kept constant at the basal level by a variable glucose infusion. Fasting C-peptide (0.29 ± 0.02 pmol/ml) fell significantly in all subjects during hyperinsulinaemia and reached a concentration of 0.19 ± 0.03 pmol/ml at 60 min and 0.14 ± 0.03 at 120 min after the start of the insulin infusion. The C-peptide response was not related to the infusion dose nor to the steady state plasma insulin concentration. It is concluded that (a) basal insulin secretion as evaluated from C-peptide measurements is inhibited by small (24 ± 3 μU/ml) physiological elevations in plasma insulin concentration independent of changes in plasma glucose, and (b) supraphysiological or even pharmacological elevations in plasma insulin do not result in a further decrease in endogenous insulin secretion above that achieved with mild hyperinsulinaemia.

Insulin secretion and substrate homeostasis in prolonged hypothermia in rats

1988 ◽  
Vol 255 (6) ◽  
pp. R1035-R1040
Author(s):  
R. Hoo-Paris ◽  
M. L. Jourdan ◽  
L. C. Wang ◽  
R. Rajotte
Keyword(s):  
Insulin Secretion ◽  
Plasma Glucose ◽  
Low Temperatures ◽  
Plasma Insulin ◽  
Glucose Utilization ◽  
Exogenous Insulin ◽  
Metabolic Substrate ◽  
Endogenous Insulin ◽  
Dose Dependent Decrease ◽  
Dose Dependent

In hypothermia, impairment of metabolic substrate mobilization and utilization may be a factor limiting survival. By use of a newly developed technique, substrate profiles and their regulation by insulin were examined in hypothermic rats (body temperature 19 degrees C) over 24 h. Plasma glucose concentrations increased to approximately 300 mg/dl during cooling and remained high throughout the period of hypothermia. Free fatty acid (FFA) concentration was not altered during cooling or during the first 10 h of hypothermia (approximately 700 mu eq/l) but progressively decreased thereafter, reaching 420 mu eq/l by 20 h. Plasma insulin decreased dramatically during cooling and remained very low (9 +/- 2 microU/ml) during the whole period of hypothermia, reflecting the suppression of insulin secretion by isolated islets at low temperatures. To test he hypothesis that suppression of endogenous insulin secretion may hamper glucose utilization and thus limit survival in hypothermia, exogenous insulin was administered. At doses of 0.1, 0.5, and 1 U/kg intravenously, insulin slowly decreased plasma glucose and FFA. However, at 0.1 and 1 U/kg intraperitoneally, insulin resulted in a dose-dependent decrease in survival time in the hypothermic rat. It is possible that the antilipolytic effect of insulin may have outweighed any beneficial effect of improving glucose utilization in hypothermia.

EFFECT OF DECAPITATION ON THE DEVELOPMENT OF INSULIN SECRETION IN THE FOETAL RABBIT

1973 ◽  
Vol 57 (1) ◽  
pp. 23-31 ◽  
Author(s):  
P. M. B. JACK ◽  
R. D. G. MILNER
Keyword(s):  
Insulin Secretion ◽  
Plasma Insulin ◽  
Insulin Concentration ◽  
Β Cell ◽  
Plasma Insulin Concentration ◽  
Intrauterine Development ◽  
Foetal Head ◽  
Significant Difference ◽  
The Mean ◽  
Control Litter

SUMMARY One rabbit foetus in a litter was decapitated on day 24 of gestation. On day 29 the litter was killed and blood was collected from all foetuses for the measurement of plasma insulin concentration. The pancreas of the decapitated foetus and that of the control litter-mate with the nearest headless body weight were cut into pieces and incubated in a physiological buffer containing 0·6 or 3·0 mg glucose/ml. The pancreas of the decapitated foetus secreted significantly more insulin than that of the control foetus in either concentration of glucose in the medium. Higher insulin secretion from the decapitated foetus persisted for 4·5 h of incubation and was demonstrable in both the first 5 and subsequent 25 min of incubation when the pancreas was initially transferred to incubation medium containing 3·0 mg glucose/ml. The mean plasma insulin concentration of the foetuses decapitated on day 24 was higher on day 29 than that of the control foetuses but there was no significant difference between the concentration of insulin in the pancreas of the two groups of animals. The results indicate that removal of the foetal head influences the intrauterine development of the rabbit β-cell.

scholarly journals Glucose–insulin relationships and thyroid status of cockerels selected for high or low residual food consumption

2000 ◽  
Vol 83 (6) ◽  
pp. 645-651 ◽  
Author(s):  
Jean-François Gabarrou ◽  
Pierre Andre Geraert ◽  
John Williams ◽  
Laurent Ruffier ◽  
Nicole Rideau
Keyword(s):  
Food Consumption ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Plasma Concentrations ◽  
Insulin Concentration ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Thyroid Status ◽  
Plasma Insulin Concentration ◽  
Diet Induced Thermogenesis

The plasma glucose–insulin relationships and thyroid status were investigated in two lines of adult cockerels divergently selected for high (R+) or low (R-) residual food consumption (RFC). For a given body weight, R+ birds had a 74 % higher food intake than R- birds. Plasma glucose concentrations were significantly lower in the R+ line compared with the R- when fasted, whereas R+ birds exhibited a significantly lower plasma insulin concentration than R- birds either in fed or fasted state. After an overnight fast, R+ birds also exhibited a higher sensitivity to exogenous insulin in view of its more pronounced hypoglycaemic effect. After an oral glucose load, the glucose disposal of R+ cockerels was faster despite lower glucose-induced plasma insulin concentration. Whilst plasma triacylglycerol concentrations were lower in the R+ line when fed, plasma non-esterified fatty acid concentrations were higher in fasted R+ than R- cockerels (684v.522 μmol/l). Higher plasma triiodothyronine concentrations were observed in fed R+ compared with R- birds (3·0v.2·1 nmol/l respectively). The higher plasma concentrations of triiodothyronine associated with lower concentrations of insulin could account for the leanness and the elevated diet-induced thermogenesis previously observed in the R+ line.

Effects of training and detraining on dose-response relationship between glucose and insulin secretion

1989 ◽  
Vol 256 (5) ◽  
pp. E588-E596 ◽  
Author(s):  
K. J. Mikines ◽  
B. Sonne ◽  
B. Tronier ◽  
H. Galbo
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Plasma Glucose ◽  
Response Relationship ◽  
Cell Secretion ◽  
Dose Response Relationship ◽  
C Peptide ◽  
Endogenous Insulin ◽  
Beta Cell Secretion ◽  
Training And Detraining

We studied the effect of training and detraining on the dose-response relationship between plasma glucose and beta-cell secretion in seven trained young men using sequential hyperglycemic clamp technique (7, 11, and 20 mM). Experiments were performed in the habitual state 15 h after last training session (T) as well as after 5 days of detraining (DT). Results were compared to data from seven untrained subjects (UT). Glucose-stimulated insulin, proinsulin, and C-peptide levels were lower in T than in UT. They increased during detraining but not to levels seen in UT. Furthermore, in T and DT, but not in UT, increases in C-peptide and proinsulin leveled off with increasing glucose concentrations. Estimated by C-peptide-to-insulin ratios, clearance of endogenous insulin was not influenced by T. Glucose uptake in tissue was the same in T, DT, and UT during clamps, despite lower insulin levels in T and DT. Differences between groups in counterregulatory hormones, fat metabolites, alanine, or electrolytes did not account for these findings. Oxygen consumption was higher in the basal state in T and DT compared with UT but increased similarly in all groups in response to glucose. Conclusions: regular physical activity causes an adaptive decrease in glucose-mediated beta-cell secretion in humans. The training-induced decrease in glucose-stimulated insulin secretion is accurately matched to increased insulin action, keeping glucose disposal constant at any given plasma glucose concentration. Finally, training increases basal metabolic rate but does not influence glucose-induced thermogenesis or clearance of endogenous insulin.

Mechanism, temporal patterns, and magnitudes of the metabolic responses to the KATP channel agonist diazoxide

2005 ◽  
Vol 288 (1) ◽  
pp. E80-E85 ◽  
Author(s):  
Bharathi Raju ◽  
Philip E. Cryer
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Fatty Acid ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Temporal Patterns ◽  
Metabolic Responses ◽  
Nonesterified Fatty Acid ◽  
Nonesterified Fatty Acids ◽  
C Peptide

To assess the mechanism, temporal patterns, and magnitudes of the metabolic responses to the ATP-dependent potassium channel agonist diazoxide, neuroendocrine and metabolic responses to intravenous diazoxide (saline, 1.0 and 2.0 mg/kg) and oral diazoxide (placebo, 4.0 and 6.0 mg/kg) were assessed in healthy young adults. Intravenous diazoxide produced rapid, but transient, decrements ( P = 0.0023) in plasma insulin (e.g., nadirs of 2.8 ± 0.5 and 1.8 ± 0.3 μU/ml compared with 7.0 ± 1.0 μU/ml after saline at 4.0–7.5 min) and C-peptide ( P = 0.0228) associated with dose-related increments in plasma glucose ( P = 0.0044) and serum nonesterified fatty acids ( P < 0.0001). After oral diazoxide, plasma insulin appeared to decline, as did C-peptide, again associated with dose-related increments in plasma glucose ( P < 0.0001) and serum nonesterified fatty acids ( P = 0.0141). Plasma glucagon, as well as cortisol and growth hormone, was not altered. Plasma epinephrine increased ( P = 0.0215) slightly only after intravenous diazoxide. There were dose-related increments in plasma norepinephrine ( P = 0.0038 and P = 0.0005, respectively), undoubtedly reflecting a compensatory sympathetic neural response to vasodilation produced by diazoxide, but these would not raise plasma glucose or serum nonesterified fatty acid levels. Thus selective suppression of insulin secretion, without stimulation of glucagon secretion, raised plasma glucose and serum nonesterified fatty acid concentrations. These findings define the temporal patterns and magnitudes of the metabolic responses to diazoxide and underscore the primacy of regulated insulin secretion in the physiological regulation of postabsorptive carbohydrate and lipid metabolism.

Effects of hyperprolactinaemia on glucose tolerance and insulin release in male and female rats

1997 ◽  
Vol 153 (3) ◽  
pp. 423-428 ◽  
Author(s):  
F M Reis ◽  
A M Reis ◽  
C C Coimbra
Keyword(s):  
Glucose Tolerance ◽  
Insulin Release ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Female Rats ◽  
Insulin Concentration ◽  
Glucose Load ◽  
Plasma Insulin Concentration ◽  
Male And Female ◽  
Male And Female Rats

Abstract It has been shown that prolactin (PRL) induces glucose intolerance, hyperinsulinaemia and insulin resistance in several animal species, including rats. However, the sex differences regarding glucose homeostasis and insulin release in hyperprolactinaemic subjects have not been assessed to date. In the present study, hyperprolactinaemic (pituitary-grafted) or control (sham-operated) male and female rats were submitted to an i.v. glucose tolerance test (30 mg/100 g body weight, 30% glucose). Grafted female rats had fasting plasma glucose concentrations 26% above control (P<0·01). After the glucose load there was a rapid and pronounced increase in plasma glucose levels in all animal groups, followed by a return to basal values within 30 min. However, the glucose concentrations in hyperprolactinaemic rats were significantly greater than those in controls at 5 min (males, P<0·05) and 30 min (females, P<0·05). The glucose disappearance rate was significantly increased in the grafted females compared with control (P<0·01) and slightly increased in the grafted males. Plasma insulin concentration increased just after glucose load and returned to basal values within 5 min in all groups except for the grafted females, which had recovered their basal insulin levels at 15 min. The grafted male rats had insulin concentrations higher than those of sham-operated controls at 2 min (28·9 ± 3·6 vs 17·3 ± 2·1 μU/ml, P<0·01), whereas females had plasma insulin concentrations greater than those in sham-operated controls 10 min after the glucose load (15·9 ± 1·9 vs 10·1 ± 1·4 μU/ml, P<0·05). The areas under the plasma insulin concentration–time curves were also significantly increased in the hyperprolactinaemic rats and were positively correlated with plasma PRL concentrations (r=0·613, P<0·01). These results demonstrate that moderate chronic hyperprolactinaemia is associated with increased glucose-induced insulin release, which was altered at different times after the glucose load in grafted male and female rats, whereas fasting hyperglycaemia was observed only in grafted females, indicating a sexual dimorphism in the diabetogenic effects of PRL in rats. Journal of Endocrinology (1997) 153, 423–428

THE EFFECT OF A HIGH-FAT DIET ON GLUCOSE, INSULIN SENSITIVITY AND PLASMA INSULIN IN RATS

1968 ◽  
Vol 42 (4) ◽  
pp. 489-494 ◽  
Author(s):  
E. BLÁZQUEZ ◽  
C. LOPEZ QUIJADA
Keyword(s):  
Plasma Glucose ◽  
High Fat Diet ◽  
Plasma Insulin ◽  
Diet Group ◽  
Insulin Concentration ◽  
Control Group ◽  
High Fat ◽  
Plasma Insulin Concentration ◽  
The Mean

SUMMARY The influence of the diet on the levels of insulin was studied in rats on a high-fat diet. Plasma and glucose insulin concentrations of a control group and of rats on a high-fat diet were compared, and so was the insulin concentration in the pancreas of the two groups. The mean plasma insulin concentration in the control group was 40 μ-u./ml. and that of insulin extracted from the pancreas was 2·5 μg./100 mg. tissue; plasma glucose was 156 mg./100 ml. The animals fed on a high-fat diet showed diabetic features. The mean plasma insulin level was 9 μ-u./ml., and plasma glucose increased to 210 mg./100 ml. The insulin concentration in the pancreas was not significantly different from that in the controls. In vitro the epididymal fat and the diaphragm of the high-fat-diet group were less sensitive to insulin than the same tissues in the control group.

Insulin secretion in hypoglycemia after adrenal vein ligature or splachnicotomy.

1977 ◽  
Vol 232 (2) ◽  
pp. E237
Author(s):  
H Sando ◽  
E Miki ◽  
K Kosaka
Keyword(s):  
Insulin Secretion ◽  
Adrenal Medulla ◽  
Plasma Glucose ◽  
Glucose Infusion ◽  
Insulin Concentration ◽  
Adrenal Vein ◽  
Major Surgery ◽  
Pancreaticoduodenal Artery ◽  
Splanchnic Nerves ◽  
Arterial Plasma

During bonito insulin-induced hypoglycemia in dogs, pancreatic venous dog insulin concentration (IRI), radioimmunoassayed differentially from bonito insulin, was progressively diminished in response to local glucose infusion (0.6 mg/kg - min) for 4 min into the superior pancreaticoduodenal artery. Basal arterial plasma glucose was significantly lower after bilateral splanchnicotomy (BSNC) than after bilateral adrenal vein ligature (BAVL). During local glucose infusion in both normoglycemia and hypoglycemia, the increment of pancreatic venous IRI was significantly greater after BAVL or BSNC than in the controls, and the increment of pancreatic venous glucose was also significantly greater after BAVL than in the controls or after BSNC. It is suggested that under the stress of major surgery the splanchnic nerves partially suppress insulin secretion in normoglycemia as well as in hypoglycemia, and epinephrine released from the adrenal medulla may interfere with glucose-mediated insulin secretion in profound hypoglycemia.

Glucose intolerance following chronic metabolic acidosis in man.

1979 ◽  
Vol 236 (4) ◽  
pp. E328 ◽  
Author(s):  
R A DeFronzo ◽  
A D Beckles
Keyword(s):  
Metabolic Acidosis ◽  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Plasma Insulin ◽  
Glucose Infusion ◽  
Insulin Concentration ◽  
Plasma Insulin Concentration ◽  
Chronic Metabolic Acidosis ◽  
Tissue Sensitivity

The effect of chronic metabolic acidosis (0.1 g/(kg . day) X 3 days) on carbohydrate metabolism was examined with the glucose-clamp technique in 16 healthy volunteers. Hyperglycemic clamp. Plasma glucose concentration is acutely raised and maintained 125 mg/dl above the basal level. Because the glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism (M). Following NH4Cl, M decreased from 8.95 +/- 1.12 to 7.35 +/- 0.76 (P less than 0.05) despite an increased plasma insulin concentration (I) 23 +/- 9%, P less than 0.05). Consequently the M/I ratio, an index of tissue sensitivity to insulin, decreased by 32 +/- 5% (P less than 0.005). Euglycemic clamp. Plasma insulin concentration is acutely raised and maintained 101 +/- 3 microU/ml above basal and plasma glucose is held constant at the fasting level by a variable glucose infusion (M). Following NH4Cl both M and M/I decreased by 15 +/- 4% (P = 0.005) and 15 +/- 5% (P = 0.01), respectively. Metabolic acidosis had no effect on basal [3-3H]glucose production or the percent of decline (91 +/- 4%) following hyperinsulinemia. Both hyperglycemic and euglycemic clamp studies indicate that impaired glucose metabolism following metabolic acidosis results from impaired tissue sensitivity to insulin.

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