Cited by 819Pancreatic function and diabetesDiabetes Treatment and ManagementDiabetes Management and Research

Insulin Secretion in Response to Glycemic Stimulus: Relation of Delayed Initial Release to Carbohydrate intolerance in Mild Diabetes Mellitus*

Open access
Seltzer, Holbrooke S., Allen, E. William, Herron, Arthur L., Brennan, Mildred T.·1967·Journal of Clinical Investigation

Abstract

Insulin secretory responses to paired intravenous and oral glucose loads were determined in 38 nonobese individuals classified as normal (nondiabetic) subjects, "mild" diabetics (fasting blood glucose below 105 mg per 100 ml), or "moderate" diabetics (fasting glucose below 192 mg per 100 ml). Studies were also performed in 29 obese persons who were similarly grouped. The intravenous load was given to assess the alacrity of hormonal release after glycemic stimulus, and the oral glucose to determine how the speed of initial insulinogenesis modifies the disposition of ingested carbohydrate. In the nonobese group, normal subjects responded to massive hyperglycemia after rapid injection of glucose with immediate and maximal outpouring of insulin, in contrast to a desultory insulinogenic response in patients with mild diabetes, and no initial response at all in moderate diabetics. During oral glucose tolerance tests, the much faster clearance of blood sugar in nondiabetic subjects was actually associated with lower absolute insulin output than was found in mildly diabetic patients, since the latter exhibited delayed hyperinsulinemia in concert with prolonged hyperglycemia. Moderate diabetics never showed excessive insulin release despite even greater hyperglycemia. An empirical "insulinogenic index," the ratio relating enhancement of circulating insulin to magnitude of corresponding glycemic stimulus, was used to compare the secretory capacities of respective groups. Despite the higher absolute hormonal output after oral glucose in mild diabetics, the index revealed that insulin release in normal subjects was proportionally more than twice as great. This relatively greater normal secretory response declared itself shortly after the administration of glucose by either route, and was maintained throughout both tests. In the 29 obese individuals, differences among groups were essentially the same as in persons of normal weight. Obese nondiabetics did show much larger absolute insulinogenic responses during both tests than did nonobese controls. Since corresponding glucose tolerance curves were also higher, the mean insulinogenic indexes for obese subjects were not statistically greater. Moreover, when comparable glucose curves of obese and nonobese controls

AI snapshot

Written from the paper’s full text.

TL;DR

In paired intravenous and oral glucose tests, mild diabetics showed delayed and blunted initial insulin release relative to normal subjects, despite later absolute hyperinsulinemia after oral glucose. The paper argues that early diabetes involves a defect in the speed and proportionality of insulin secretion per glycemic stimulus, not simply a reduced total amount.

Key findings

  • After intravenous glucose, nonobese normal subjects had immediate maximal insulin release: blood glucose rose from 72 ± 1 to 296 ± 7 mg/100 ml and plasma insulin from 10 ± 1 to 142 ± 14 µU/ml (p < 0.001). Mild diabetics reached a similar 5-minute glucose level (294 ± 17 mg/100 ml) but insulin rose only from 12 ± 2 to 45 ± 9 µU/ml and plateaued at 47 ± 8 µU/ml; moderate diabetics showed no initial insulin rise.
  • During oral glucose testing, mild diabetics had delayed hyperinsulinemia: glucose rose from 80 ± 3 to 201 ± 11 mg/100 ml at 60 minutes, while insulin rose from 9 ± 2 µU/ml to a delayed peak of 233 ± 42 µU/ml at 90 minutes. Normal subjects cleared glucose faster with a lower absolute insulin peak (129 ± 10 µU/ml at 45 minutes).
  • The “insulinogenic index” (insulin increment area divided by glucose increment area) was lower in diabetics. For the total intravenous test, nonobese values were 0.66 ± 0.07 (100%) in normals, 0.31 ± 0.06 (47%) in mild diabetics, and 0.12 ± 0.04 (18%) in moderate diabetics; total oral values were 4.93 ± 0.54 (100%), 2.43 ± 0.39 (49%), and 0.47 ± 0.13 (10%), respectively.
  • Obese subjects showed the same group patterns. Obese normals had larger absolute insulin responses, but their insulinogenic indexes were not statistically greater than nonobese normals because their glucose curves were also higher. Total intravenous indexes in obese subjects were 1.12 ± 0.25 (100%) in normals, 0.67 ± 0.08 (60%) in mild diabetics, and 0.19 ± 0.07 (17%) in moderate diabetics; oral indexes were 5.45 ± 0.69 (100%), 2.17 ± 0.21 (40%), and 0.58 ± 0.23 (11%).

Methods

  • Paired intravenous and oral glucose loads were given to 38 nonobese individuals (21 normal, 10 mild diabetics, 7 moderate diabetics) and 29 obese individuals (11 normal, 11 mild diabetics, 7 moderate diabetics). Mild diabetes was defined as fasting blood glucose below 105 mg/100 ml; moderate diabetes as fasting glucose between 106 and 192 mg/100 ml.
  • Intravenous glucose was 0.5 g/kg actual body weight injected over exactly 5 minutes; oral glucose was 1.75 g/kg desirable body weight consumed within 5 minutes. Blood glucose was measured by the Somogyi-Nelson method, and plasma insulin by a modification of the Yalow-Berson radioimmunoassay.
  • Secretory responses were compared using plasma insulin and blood glucose patterns, insulin:glucose ratios, and an empirical “insulinogenic index” calculated as the area under the insulin increment curve divided by the area under the glucose increment curve over cumulative intervals.

Limitations

  • The paper states that its interpretations depend on “unprovable but reasonable assumptions”: that immunoassayable insulin equals biological activity, that antecubital venous glucose reflects pancreatic arterial glucose, and that antecubital venous plasma insulin reflects pancreatic venous plasma insulin.
  • The paper states that different dosage schedules for intravenous and oral tests “prevented strict comparison of the two secretory patterns for each person.” It also states that the precise nature of the lesion making diabetic islets hyporesponsive to rising glucose remains unknown.
  • Evident from the text: the moderate diabetic groups were small (7 nonobese and 7 obese), and the study population was almost entirely men (only 3 nonobese normal women and 1 nonobese woman with mild diabetes).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1172/jci105534

Cites

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Statistics

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Claims the paper makes

0 of 30 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Moderate diabetics never showed excessive insulin release despite even greater hyperglycemia.

    “Moderate dia- betics never showed excessive insulin release despite even greater hypergly- cemia.”
    Quote in the paperSubstantial claim
  • Findingown data

    In moderate diabetics, initial insulin release during the oral glucose tolerance test was virtually absent.

    “whereas in moderate diabetics it was virtually absent.”
    Quote in the paperSubstantial claim
  • Findingown data

    When the highest glucose curves in normal weight controls were matched with the lowest ones in obese subjects, the substantial difference that persisted between mean insulin patterns on both tests was again insignificant.

    “When the latter presumed determinant of insulino- genesis was eliminated by matching the highest glucose curves in normal weight controls with the lowest ones in obese subjects (Figure 6), the substantial difference that persisted between mean insulin patterns on both tests was again insig- nificant.”
    Quote in the paperSubstantial claim
  • Findingown data

    Values obtained from antecubital venous blood indicated that at least the early insulinogenic response seemed directly related to glucose concentration, irrespective of pool size and other kinetics of glucose and insulin turnover.

    “It was gratifying that values obtained from antecubital venous blood indicated that at least the early insulinogenic response seemed directly re- lated to glucose concentration, irrespective of pool size and other kinetics of glucose and insulin turnover.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Events in the peripheral circulation of man reflect those occurring in the pancreas.
  • Findingown data

    At the end of the 5-minute intravenous glucose injection into normal subjects, the rise in blood glucose from 72 ± 1 to 296 ± 7 mg per 100 ml was paralleled by an increase in plasma insulin from 10 ± 1 to 142 ± 14 μU per ml (p < 0.001).

    “At the end of the 5-min- ute injection into normal subjects, the rise in blood glucose from 72 + 1 mg per 100 ml (mean ± SEM) to 296 + 7 mg per 100 ml was paralleled by an increase in plasma insulin from 10 ± 1 ,uU per ml to 142 ± 14 puU per ml (p < 0.001).”
    Quote in the paperSubstantial claim
  • May combine two claims. 28
  • The quote only partly states this claim. 2
  • Classified as probably not a substantial claim. 12
  • May combine two claims.

    Findingown data

    Mildly diabetic patients exhibited delayed hyperinsulinemia in concert with prolonged hyperglycemia during oral glucose tolerance tests.

    “since the latter exhibited delayed hyperinsulinemia in concert with prolonged hyperglycemia.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Whether blood glucose descended from an acutely imposed hyperglycemic apex or first rose and then fell postprandially, the insulin secretory response was always much greater in normal subjects than in mild diabetics, and was even lower in moderate diabetics.

    “The findings in Table V in- dicate that whether blood glucose descended from an acutely imposed hyperglycemic apex, or first rose and then fell postprandially, the insulin se- cretory response was always much greater in nor- mal subjects than in mild diabetics, and was even lower in moderate diabetics.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Both the speed of insulin release and the quantity of insulin secreted per unit of glycemic stimulus are much greater in normal subjects than in the mildest diabetic patients, in both nonobese and obese individuals.

    “We found that both the speed of insulin release and the quantity of insulin secreted per unit of gly- cemic stimulus are much greater in normal sub- jects than in the mildest diabetic patients, in both nonobese and obese individuals.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingnone given

    Although obese nondiabetics and mild diabetics tended to produce higher plasma insulin concentrations after both glucose loads, they otherwise exhibited the same patterns of insulinogenic response as their nonobese counterparts.

    “In general, although obese nondiabetics and mild diabetics tended to produce higher plasma insulin concentrations after both glucose loads, they otherwise exhibited the same patterns of in- sulinogenic response as their nonobese counter- parts.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    During the oral glucose tolerance test in nonobese individuals, the insulinogenic index for the first 30 minutes was 3.07 ± 0.34 in normal controls and 1.14 ± 0.21 in mild diabetics, and respective indexes for the entire test were 4.93 ± 0.54 and 2.43 ± 0.39.

    “For example, during the oral glucose tolerance test in nonobese individuals the index (Table V) for the first 30 minutes was 3.07 + 0.34 in normal controls and 1.14 ± 0.21 in mild diabetics (p < 0.001), and respective indexes for the entire test were 4.93 ± 0.54 and 2.43 ± 0.39 (p < 0.001).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    When individual secretory response was expressed per unit of glycemic stimulus, the much greater absolute hyperinsulinemia of obesity lost statistical meaning because glucose tolerance of overweight subjects was sufficiently higher than in nonobese controls.

    “Even including them, however, when individual secretory response was expressed per unit of glycemic stimulus, the much greater absolute hyperinsulinemia of obesity lost statistical meaning (Table V) because glucose tolerance of overweight subjects, albeit still normal, was sufficiently higher than in nonobese controls.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Normal subjects responded immediately and maximally to the massive glycemic stimulus, in contrast to progressively blunted secretory responses in the diabetic groups.

    “Normal subjects responded immediately and max- imally to the massive glycemic stimulus, in con- trast to progressively blunted secretory responses in the diabetic groups.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    For the initial 30 minutes after oral glucose, the mean insulin:glucose ratio for control subjects was 3.37 ± 0.32, and the corresponding value for mild diabetics was 1.28 ± 0.14 (p < 0.001).

    “For the initial 30 min- utes after oral glucose, the mean ratio for control subjects was 3.37 + 0.32, and the corresponding value for mild diabetics was 1.28 + 0.14 (p < 0.001).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingreasoning

    Mean insulinogenic indexes for obese subjects were not statistically greater than those for nonobese controls, since corresponding glucose tolerance curves were also higher.

    “Since corresponding glucose tolerance curves were also higher, the mean insulinogenic indexes for obese subjects were not statistically greater.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    In moderate diabetics, mean fasting glucose of 126 ± 8 mg per 100 ml rose to 342 ± 17 mg per 100 ml in 5 minutes with no increase above the fasting plasma insulin level of 24 ± 5 μU per ml.

    “In moderate dia- betics, mean fasting glucose of 126 + 8 mg per 100 ml rose to 342 + 17 mg per 100 ml in 5 min- utes with no increase above the fasting plasma in- sulin level of 24 5 ,uU per ml”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    In the mild diabetics, fasting blood glucose was below 100 mg per 100 ml in 15 patients and less than 105 mg per 100 ml in the other 6; in all individuals blood glucose exceeded 160 mg per 100 ml at 1 hour and was well above 120 mg per 100 ml at 2 hours.

    “In the mild diabetics, fasting blood glucose was below 100 mg per 100 ml in 15 patients and less than 105 mg per 100 ml in the other 6; in all individuals blood glucose exceeded 160 mg per 100 ml at 1 hour and was well above 120 mg per 100 ml at 2 hours.”
    Quote in the paperSubstantial claim
  • May combine two claims. The quote only partly states this claim.

    Findingown data

    In mild diabetics, the 5-minute blood glucose level of 294 ± 17 mg per 100 ml elicited only a modest rise of plasma insulin from a fasting value of 12 ± 2 to 45 ± 9 μU per ml (p < 0.001 compared to the 5-minute value in normal subjects), and plasma insulin plateaued at a maximum of 47 ± 8 μU per ml as circulating glucose slowly receded to the normal fasting range by 120 minutes.

    “100 ml elicited only a modest rise of plasma insulin from a fasting value of 12 + 2 ,uU per ml to 45 + 9 ,uU per ml (p < 0.001 compared to the 5-minute value in normal subjects), and plasma insulin plateaued at a maximum of 47 + 8 fLU per ml as circulating glucose slowly receded to the normal fasting range by 120 minutes.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingreasoning

    In the moderate diabetics, since fasting glucose was always higher than 105 mg per 100 ml, blood levels 1 and 2 hours after the oral glucose load greatly exceeded 160 mg per 100 ml and 120 mg per 100 ml, respectively.

    “In the moderate diabetics, since fasting glucose was always higher than 105 mg per 100 ml, blood levels 1 and 2 hours after the oral glu- cose load greatly exceeded 160 mg per 100 ml and 120 mg per 100 ml, respectively.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    During the first 10 minutes after intravenous glucose, the mean insulin:glucose ratio for normal subjects was 0.56 ± 0.03, and the corresponding ratio in mild diabetics was 0.22 ± 0.06 (p < 0.001).

    “During the first 10 minutes after intravenous glucose, the mean ratio for normal subjects was 0.56 + 0.03, and the corresponding ratio in mild diabetics was 0.22 + 0.06 (p < 0.001).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Thereafter, in normal subjects, blood glucose dropped rapidly to a normal fasting level by 60 minutes, accompanied by a similar swift decline in circulating insulin concentration.

    “Thereafter, blood glucose dropped rapidly to a normal fasting level by 60 minutes, accompanied by a similar swift decline in circulating insulin concentration.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    For the intravenous test, the total insulinogenic index was 0.66 ± 0.07 (100%) for normal subjects, 0.31 ± 0.06 (47%) for mild diabetics, and 0.12 ± 0.04 (18%) for moderate diabetics.

    “For the intravenous test, the”
    Quote in the paperSubstantial claim
  • May combine two claims. The quote only partly states this claim.

    Findingown data

    In mild diabetics during the oral glucose test, fasting blood glucose of 80 ± 3 mg per 100 ml rose to 201 ± 11 mg per 100 ml in 60 minutes, then fell slowly to 155 ± 12 mg per 100 ml at 120 minutes and to 108 ± 14 mg per 100 ml at 180 minutes.

    “100 ml in 60 minutes, then fell slowly to 155 + 12 mg per 100 ml at 120 minutes and to 108 + 14 mg per 100 ml at 180 minutes.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Corresponding over-all insulinogenic indexes after oral glucose were 4.93 ± 0.54 (100%), 2.43 ± 0.39 (49%), and 0.47 ± 0.13 (10%).

    “Corresponding over-all indexes after oral glucose were 4.93 + 0.54 (100o), 2.43 ± 0.39 (49%o), and 0.47 +0.13 (10%o).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    The relatively greater normal secretory response declared itself shortly after administration of glucose by either route and was maintained throughout both tests.

    “This relatively greater normal secretory response de- clared itself shortly after the administration of glucose by either route, and was maintained throughout both tests.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Despite higher absolute hormonal output after oral glucose in mild diabetics, the insulinogenic index revealed that insulin release in normal subjects was proportionally more than twice as great.

    “Despite the higher absolute hormonal output after oral glucose in mild diabetics, the index revealed that insulin release in normal subjects was proportionally more than twice as great.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    In moderate diabetics during the oral glucose test, as fasting blood glucose of 137 ± 11 mg per 100 ml rose to a peak value of 295 ± 27 mg per 100 ml at 90 minutes and then declined to 211 ± 42 mg per 100 ml at 240 minutes, plasma insulin rose sluggishly from a control value of 19 ± 5 to 103 ± 29 μU per ml at 120 minutes.

    “In the moderate diabetics, as fasting blood glucose of 137 ± 11 mg per 100 ml rose to a peak value of 295 ± 27 mg per 100 ml at 90 minutes and then declined to 211 ± 42 mg per 100 ml at 240 minutes, plasma insulin rose sluggishly from a control value of 19 ± 5 ,uU per ml to 103 + 29 ptU per ml at 120 minutes.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    The present findings did show much greater insulin release after oral glucose loads in all three clinical groups, and regardless of body weight.

    “Nevertheless, the present findings did show much greater insulin release after oral glucose loads in all three clinical groups, and regardless of body weight.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Each patient was given intravenous and oral glucose in random order and at intervals of a few days.

    “each patient was given intravenous and oral glucose, in random order and at intervals of a few days.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Current work has narrowed the active substance down to glucagon, secretin, or pancreozymin.

    “Current work has narrowed the active substance down to glucagon (22), secretin (23-25), or pancreozymin (26).”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [22]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [23]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [24]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [25]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [26]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S1 (asserted).

    Premisecitation

    Symptomatic postprandial hypoglycemia in patients with mild diabetes mellitus might be due to delayed initial release of insulin followed by subsequent excessive hormonal secretion.

    “the interpretation in- voked by Seltzer, Fajans, and Conn (3), that the occurrence of symptomatic postprandial hypogly- cemia in patients with mild diabetes mellitus might be due to delayed initial release of insulin followed by subsequent excessive hormonal secretion”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Seltzer, Fajans, and Conn (3)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    An acute rise or fall of blood glucose level directly induces an increase or decrease, respectively, of insulin release.

    “An acute rise or fall of blood glucose level directly induces an increase or decrease, respec- tively, of insulin release (1, 2, 8, 9).”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [1]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [2]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [8]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [9]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In a carefully controlled study of comparably mild diabetics, Perley and Kipnis concluded that the diabetic state is associated with reduced insulin secretory capacity, regardless of body weight.

    “In a carefully controlled study of comparably mild diabetics, Perley and Kipnis (16) also concluded that the diabetic state is associated with reduced insulin secretory capacity, regardless of body weight.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data

    The finding that plasma insulin became significantly higher in obese mild diabetics at 20 minutes after intravenous glucose suggested an anti-insulin effect of obesity.

    “which finding again sug- gested an anti-insulin effect of obesity.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The general phenomenon of greater hormonal response to glucose loads in overweight normal subjects suggests that the obese state somehow engenders peripheral insulin resistance.

    “At the same time, the general phenome- non of greater hormonal response to glucose loads in overweight normal subjects did suggest that the obese state somehow engenders peripheral in- sulin resistance (14, 15).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [15]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Glucose-induced insulinogenesis does not alter pancreatic venous blood flow.

    “previous work (2) having established that glucose-induced insulinogenesis does not alter pancreatic venous blood flow.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Three of these groups suggested that assimilation of carbohydrate in the upper intestine stimulates release of a humoral agent that enhances the insulin-releasing potency of blood glucose level per se.

    “Three of these groups suggested that assimilation of carbohydrate in the upper intestine stimulates release of a humoral agent that enhances the insulin-releasing potency of blood glucose level per se.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Yalow and Berson found subnormal plasma insulin concentrations at 30 minutes during glucose tolerance testing of mild diabetics but supernormal levels at 2 hours.

    “Yalow and Berson (4) found subnormal plasma insulin concentrations at 30 minutes during glucose toler- ance testing of mild diabetics but supernormal levels at 2 hours.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Yalow and Berson (4)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The dose-response curve, the reproducibility of values when the same plasma samples were repeatedly assayed, and the range of values obtained in normal and diabetic patients all duplicated the performance of the original radioimmunoassay technique.

    “The dose-response curve, the reproducibility of values when the same plasma samples were repeatedly assayed, and the range of values obtained in normal and diabetic patients all duplicated the performance of the original technic.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Premisecitation

    During continuous changes in circulating glucose concentrations after carbohydrate loads, the rate of insulin secretion is directly, but not necessarily linearly, proportional to the simultaneous blood glucose level.

    “During continuous changes in circulating glucose concentrations after carbohydrate loads, the rate of insulin secretion is di- rectly (but not necessarily linearly) proportional to the simultaneous blood glucose level.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Metz (1)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationown data

    In its initial stage, diabetes mellitus remains fundamentally a disease of deficient insulin secretion, but one of rate rather than magnitude.

    “In this respect diabetes melli- tus remains fundamentally a disease of deficient insulin secretion, but one of rate rather than mag- nitude in the initial stage of the disease.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationreasoning

    The blunted capability of mildly diabetic islets to release insulin after the same intravenous bolus of glucose implied an obtunded islet response to oral glucose as well, which relative lack of early insulin activity on hepatic and posthepatic tissues could reasonably account for the delay in metabolizing ingested glucose.

    “Conversely, the blunted capability of mildly diabetic islets to re- lease insulin after the same intravenous bolus of glucose implied an obtunded islet response to oral glucose as well-which relative lack of early in- sulin activity on hepatic and posthepatic tissues could reasonably account for the delay in metabo- lizing ingested glucose.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationcitation

    Normal immediate hormonal release after sudden intense hyperglycemia suggested that a similarly fast response, but smaller and peripherally undetectable, was also activated by postprandially rising blood sugar, and this brisk insulinogenesis should promote avid hepatic and peripheral glucose uptake, which in turn would clear absorptive hyperglycemia with dispatch.

    “Normal immediate hormonal release after sudden intense hyperglycemia suggested that a similarly fast response, but smaller and peripherally unde- tectable, was also activated by postprandially rising blood sugar, and this brisk insulinogenesis should promote avid hepatic and peripheral glucose up- take (27), which in turn would clear absorptive hyperglycemia with dispatch.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

37 of 37
  • The authors state this as an assumption.

    The concentration of glucose in antecubital venous blood is directly proportional to the concomitant glucose level in pancreatic arterial blood.

    “the concentration of glucose in antecubital venous blood is directly proportional to the concomitant glucose level in pancreatic arterial blood”
  • The authors state this as an assumption.

    The insulin content of antecubital venous plasma directly reflects the simultaneous concentration in pancreatic venous plasma.

    “the insulin content of antecubital venous plasma directly reflects the simul- taneous concentration in pancreatic venous plasma.”
  • The authors state this as an assumption.

    Events in the peripheral circulation of man reflect those occurring in the pancreas.

    “Assuming that events in the peripheral circulation of man reflect those occurring in the pancreas”
  • The paper relies on this without support.

    Frequently monitored peripheral plasma insulin concentrations reflect actual insulin secretion.

    “to the extent that frequently monitored peripheral plasma insulin concentra- tions reflected actual insulin secretion”
4 of 4

Cites

Flagged first, then by citations

3 of the 30 references couldn’t be matched to a known paper.

Research works printed but not linked: 4

  1. Elrick, H., L. Stimmler, C. J. Hlad, Jr., and Y. Arai. Plasma insulin response to oral and intra- venous glucose administration. J. clin. Endocr. 1964, 24, 1076.
  2. Dupre, J. Effect of route of administration on dis- posal of glucose loads. J. Physiol. (Lond.) 1964, 175, 58.
  3. Ketterer, H., A. Ohneda, J. Dupre, A. Eisentraut, and R. H. Unger. Effects of enteric hormones on insulin and glucagon secretion. J. Lab. clin. Med. 1966, 68, 888.
  4. Schonfeld, G., and D. M. Kipnis. Studies of extra- cellular and tissue fatty acid pools and glucose metabolism in striated muscle. J. clin. Invest. 1966, 45, 1071.

Cited by

Sorted by citations

Authors
Seltzer, H. S., Allen, E. W., Herron, A. L., & Brennan, M. T.
Affiliations
United States Department of Veterans Affairs (US)
Venue
Journal of Clinical Investigation
Published
1967-03-01
Volume
46
Issue
3
Pages
323-335
ISSN
0021-9738 (ISSN-L)
OpenAlex
W2110124224
Cited by
819
References
30
Citations by year
2026: 12 · 2025: 12 · 2024: 26 · 2023: 15 · 2022: 16 · 2021: 18 · 2020: 18 · 2019: 13 · 2018: 26 · 2017: 25 · 2016: 24 · 2015: 18 · 2014: 25 · 2013: 24 · 2012: 10
FWCI
90.80
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
insulin secretion, carbohydrate intolerance, oral glucose tolerance, intravenous glucose tolerance, hyperinsulinemia, hyperglycemia, obesity, insulinogenic index
MeSH terms
Adult, Aged, Blood Glucose, Body Weight, Diabetes Mellitus, Female, Glucose, Glucose Tolerance Test, Humans, Insulin, Male, Middle Aged, Obesity, Carbohydrate Metabolism

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-14.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-14.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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