Measurement of the Insulin Delivery Rate in Man

Turner, R. C.; Grayburn, J. A.; Newman, G. B.; Nabarro, J. D. N.

doi:10.1210/jcem-33-2-279

Cited by 125 publications

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“…An approximate doubling of plasma insulin levels after sulphonylurea was also found at a standard plasma glucose concentration 2mmol/1 higher than the original fasting level. The more precise C-peptide assay showed a consistent increase of B-cell secretion on sulphonylureas, although the individual percentage increase of mean C-peptide was less than the insulin rise over 60 min, reflecting the longer C-peptide plasma half-life [19,20] and hence a slower increase in plasma concentration.…”

Section: Discussionmentioning

confidence: 91%

Sulphonylurea therapy doubles B-cell response to glucose in Type 2 diabetic patients

et al. 1985

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Summary. The effect of sulphonylurea therapy for 3 weeks on glucose-stimulated insulin secretion and insulin resistance was studied in Type 2 diabetic patients. The fasting plasma insulin and C-peptide concentrations on diet alone were compared with each subject's fasting concentrations on sulphonylurea treatment at a lower fasting plasma glucose and at the original diet-alone glycaemic level obtained by the hyperglycaemic clamp technique. At this isoglycaemic level (mean 11 mmol/1), plasma insulin levels increased from 6.9 mU/1 on diet alone to 12.1 mU/1 on sulphonylurea treatment (p< 0.01). The subjects were also studied by the hyperglycaemic clamp technique at mean glycaemic levels of 13 retool/1 before and after sulphonylurea treatment; the incremental insulin response was similarly enhanced from 7.6_+3.5 to 13.7+_ 6.9 mU/1 (p < 0.02) respectively. Sulphonylureas appear to reduce glycaemia by enhancing B-cell function two-fold. In the patients studied this was from approximately 21% to 37% of a normal response. Insulin resistance assessed by the same hyperglycaemic clamps as endogenous plasma insulin concentrations divided by glucose infusion rates was unchanged by sulphonylurea therapy (mean 4.37 compared to 4.40mU-1 -1. mg-1. kg-rain on diet alone).

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Section: Discussionmentioning

confidence: 91%

Sulphonylurea therapy doubles B-cell response to glucose in Type 2 diabetic patients

et al. 1985

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“…There have been attempts to estimate the rate of insulin secretion by indirect methods: the evaluation of the rate of degradation of insulin under steady state conditions [2,11,45]; the comparison of plasma IRI values after a rapidly acting secretory stimulus with those after an exogenous insulin load [41]; and the estimation according to a "reciprocal" indicator dilution principle with insulin as an indicator [46]. Repeated estimations, however, are not possible by these methods.…”

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confidence: 99%

Estimation of pancreatic IRI output rate and its relation to glucose tolerance in normal anaesthetized dogs

et al. 1975

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Summary. The pancreaticoduodenal and portal venous blood flows were recorded electromagnetically in anaesthetized dogs. Blood glucose and IRI were measured in the arterial, portal, and peripheral venous as well as in the intestinal venous blood. By a mathematical model the actual net IRI output of the whole pancreas was estimated. Under basal conditions it is 10.2 + 2.4 mU/min (n = 30; 26 kg mean body wt.). After i.v. glucose injection, IRI output is rapidly enhanced. The biphasic nature of this reaction was unequivocally demonstrated by consideration of the ratio IRI output : blood glucose. Pancreaticoduodenal blood flow increases transiently in relation to the increased blood glucose concentration. The IRI secretion rate is well correlated with the blood glucose concentration and to the amounts of glucose or of blood reaching the whole pancreas. It is also correlated with the portal IRI concentration. The overall peripheral venous or arterial IRI concentrations are correlated with the IRI secretion rate, but not in all individual experiments. The different phases of IRI output (basal rate, stimulated output 1-10 min and 10-60 min) show no influence on each other, nor are they correlated with the peripheral IRI concentration area. Basal IRI output is negatively correlated with the glucose assimilation constants. These constants or the peripheral BG areas, however, are independent of the stimulated IRI output rate. However, both the assimilation constants and the peripheral BG areas are related to the peripheral IRI concentration areas. Hepatic uptake of insulin and dynamics of pancreatic blood flow seem to contribute considerably to the estimated correlation pattern.

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“…Thus, the over-all disappearance of the initial phase, evaluated on the basis of clinical study, was used to calculate the post-hepatic insulin delivery rate. To avoid any potential effect of hypoglycaemia on insulin disappearance [11][12][13][14], glucose was also administered intravenously. Constantly infused glucose used in our procedure has been reported to reduce markedly hepatic glucose output without a concomitant increase in total glucose utilization [17,18].…”

Section: Discussionmentioning

confidence: 99%

“…The measurement of the disappearance rate of unlabelled insulin may be complicated by the fact that plasma glucose concentration is decreased. The influence of hypoglycaemia on the disappearance rate of insulin, however, is generally considered insignificant [11][12][13][14], even if endogenous insulin is unchanged or suppressed. It has been reported that the absolute degradation rate of insulin is proportional to the plasma insulin concentration, i.e.…”

Section: Methodsmentioning

confidence: 99%

“…the fractional rate is constant [15]. Although several authors have shown that the irreversible loss rate of insulin is not linearly related to plasma concentration [13][14][15], the difference is not very large, and it is reasonable to assume that the fractional rate of loss of unlabelled insulin is relatively constant regardless of the plasma concentrations. Therefore, it is reasonable to assume that the calculated rate of insulin removal, following a single dose of insulin, can be applied to the delivery of various amounts of insulin following glucose or arginine infusion.…”

Section: Methodsmentioning

confidence: 99%

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Insulin delivery rate in response to glucose and arginine infusion in hyperthyroidism

Asano

Okumura

1982

Diabetologia

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Summary. Insulin delivery rates were estimated from the peripheral serum insulin response to a single bolus injection of glucose or arginine in eight normal subjects and eight patients with hyperthyroidism. The mean rate constant for insulin disappearance was 0.2380 _+ 0.0052 per min in the control subjects, which was not significantly different from that observed in the patients with hyperthyroidism (0.2147 _+ 0.0111 per rain). There were also no significant differences in the insulin response to glucose infusion (1.7 _+ 0.3 U during the first phase (0-I0 min) and 5.6 +_ 1.6 U during the second phase (11-60 min) in normal subjects compared with 1.2 _+ 0.5 and 3.7 _+ 1.1 U respectively in the hyperthyroid patients). The delivered insulin in response to glucose infusion was similar in the two.groups. The kg-value in the patients with hyperthyroidism was lower than that in the control subjects (1.24 _ 0.11 versus 2.11 _+ 0.22; p < 0.005). In hyperthyroidism, the low kg-value was not a result of the diminished insulin delivery to the general circulation. Insulin delivery showed a monophasic pattern following arginine infusion in both patients and control subjects. For the control subjects, the amount of insulin delivered was estimated to be 0.53 + 0.12 U during the first 10 min and 0.37 _+ 0.14 U during 11-30 min. In hyperthyroidism, the amount of insulin delivered was significantly lower than in the control subjects (0.21 _+ 0.06 U during the first 10 min and 0.07 _+ 0.03 U during 11-30 min). In the control subjects, the plasma glucose level was raised transiently following arginine infusion, but in hyperthyroidism, there was no change in plasma glucose levels. In hyperthyroidism, therefore, glucose intolerance appears to be primarily related to an antagonism of the hepatic effect of insulin by thyroxine rather than an inhibitory effect of thyroxine on insulin secretion. However, since delivery rate represents the measurement of peripheral serum insulin concentrations, these results cannot exclude an abnormality of hepatic insulin metabolism in hyperthyroidism.Key words: Insulin delivery rate, insulin secretion in hyperthyroidism, glucose, arginine, insulin disappearance rate.Glucose tolerance and insulin secretion have been examined extensively in hyperthyroidism [1][2][3][4], and a reduced glucose tolerance has been found in patients with this condition [2,3]. However, intravenous glucose infusions in hyperthyroid men or dogs have produced conflicting results concerning plasma insulin secretion [2][3][4][5].The mechanism of glucose intolerance is uncertain. It could be a consequence of a decreased capacity of insulin secretion or increased insulin catabolism [6]. In the present study, we have measured insulin delivery rates, calculated on the basis of fractional insulin disappearance rates following glucose infusion, in order to understand further B cell function in hyperthyroidism. Since the arginine-induced insulin response has been reported to be impaired in hyperthyroidism [7], the effect of arginine on the ...

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Measurement of the Insulin Delivery Rate in Man

Cited by 125 publications

References 0 publications

Sulphonylurea therapy doubles B-cell response to glucose in Type 2 diabetic patients

Sulphonylurea therapy doubles B-cell response to glucose in Type 2 diabetic patients

Estimation of pancreatic IRI output rate and its relation to glucose tolerance in normal anaesthetized dogs

Insulin delivery rate in response to glucose and arginine infusion in hyperthyroidism

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