Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose.

Bergman, Richard N.; Phillips, Lawrence S.; Cobelli, Claudio

doi:10.1172/jci110398

Cited by 1,497 publications

(1,010 citation statements)

References 28 publications

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“…This Δ insulin secretion was calculated both without and with trimethaphan. Figure 3 shows that dexamethasone substantially increased AIR 1 …”

Section: Resultsmentioning

confidence: 99%

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Evidence that autonomic mechanisms contribute to the adaptive increase in insulin secretion during dexamethasone-induced insulin resistance in humans

Åhrén

2008

Diabetologia

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Aims/hypothesis This study examined whether autonomic mechanisms contribute to adaptively increased insulin secretion in insulin-resistant humans, as has been proposed from studies in animals. Methods Insulin secretion was evaluated before and after induction of insulin resistance with or without interruption of neural transmission. Insulin resistance was induced by dexamethasone (15 mg given over 3 days) in nine healthy women (age 67 years, BMI 25.2±3.4 kg/m 2 , fasting glucose 5.1± 0.4 mmol/l, fasting insulin 46±6 pmol/l). Insulin secretion was evaluated as the insulin response to intravenous arginine (5 g) injected at fasting glucose and after raising glucose to 13 to15 mmol/l or to >28 mmol/l. Neural transmission across the ganglia was interrupted by infusion of trimethaphan (0.3-0.6 mg kg −1 min −1 ). Results As an indication of insulin resistance, dexamethasone increased fasting insulin (to 75±8 pmol/l, p<0.001) without significantly affecting fasting glucose. Arginine-induced insulin secretion was increased by dexamethasone at all glucose levels (by 64±12% at fasting glucose, by 80± 19% at 13-15 mmol glucose and by 43±12% at >28 mmol glucose; p<0.001 for all). During dexamethasone-induced insulin resistance, trimethaphan reduced the insulin response to arginine at all three glucose levels. The augmentation of the arginine-induced insulin responses by dexamethasoneinduced insulin resistance was reduced by trimethaphan by 48±6% at fasting glucose, 61±8% at 13-15 mmol/l glucose and 62±8% at >28 mmol/l glucose (p<0.001 for all). In contrast, trimethaphan did not affect insulin secretion before dexamethasone was given. Conclusions/interpretations Autonomic mechanisms contribute to the adaptative increase in insulin secretion in dexamethasone-induced insulin resistance in healthy participants.

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“…This Δ insulin secretion was calculated both without and with trimethaphan. Figure 3 shows that dexamethasone substantially increased AIR 1 …”

Section: Resultsmentioning

confidence: 99%

“…Insulin secretion is increased by insulin resistance [1][2][3]. This compensation is of critical importance, because a failure of the islets to adequately respond with increased insulin secretion in insulin resistance is a key factor in the development of type 2 diabetes [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Evidence that autonomic mechanisms contribute to the adaptive increase in insulin secretion during dexamethasone-induced insulin resistance in humans

Åhrén

2008

Diabetologia

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“…It has been documented that the body adapts to insulin resistance by a compensatory increase in insulin secretion [3,[18][19][20][21]. This concept is important for understanding the key role of the islet beta cells for the development of IGT and type 2 diabetes: if beta cell compensation to insulin resistance fails, glucose homeostasis deranges, which will result in IGT and type 2 diabetes [3].…”

Section: Discussionmentioning

confidence: 99%

Glucagon secretion in relation to insulin sensitivity in healthy subjects

Åhrén

2005

Diabetologia

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Aims/hypothesis: The study evaluated whether glucagon secretion is regulated by changes in insulin sensitivity under normal conditions. Materials and methods: A total of 155 healthy women with NGT (aged 53-70 years) underwent a glucose-dependent arginine-stimulation test for evaluation of glucagon secretion. Arginine (5 g) was injected i.v. under fasting conditions (plasma glucose 4.8±0.1 mmol/l) and after raising blood glucose concentrations to 14.8±0.1 and 29.8±0.2 mmol/l. The acute glucagon response (AGR) to arginine during the three glucose levels (AGR 1 , AGR 2 , AGR 3 ) was estimated, as was the suppression of baseline glucagon by the increased glucose. All women also underwent a 2-h euglycaemic-hyperinsulinaemic clamp study for estimation of insulin sensitivity. Results: Insulin sensitivity was normally distributed, with a mean of 73.2±29.3 (SD) nmol glucose kg −1 min −1 /pmol insulin l −1 . When relating the variables obtained from the arginine test to insulin sensitivity, insulin resistance was associated with increased AGR and with increased suppression of glucagon levels by glucose. For example, the regression between insulin sensitivity and AGR 2 was r=−0.38 (p<0.001) and between insulin sensitivity and suppression of glucagon levels by 14.8 mmol/l glucose r=0.36 (p<0.001). Insulin sensitivity also correlated negatively with insulin secretion; multivariate analysis revealed that changes in insulin sensitivity and insulin secretion were independently related to changes in glucagon secretion. Conclusions/ interpretation: The body adapts to insulin resistance by increasing the glucagon response to arginine and by increasing the suppression of glucagon levels by glucose. Hence, not only the islet beta cells but also the alpha cells seem to undergo compensatory changes during the development of insulin resistance.

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“…0‐10 minutes post‐glucose load). S i was determined using the minimal model (MLAB software)24 and the disposition index (IVGTT‐DI) was calculated as the product of AIRg and S i. 22 Blood was taken for measurement of glucose, insulin, kisspeptin, luteinising hormone (LH), testosterone, glucagon‐like peptide‐1 (GLP‐1), peptide‐YY (PYY), glucagon and cortisol.…”

Section: Methodsmentioning

confidence: 99%

The effects of kisspeptin on β‐cell function, serum metabolites and appetite in humans

Izzi‐Engbeaya

Comninos

Clarke

et al. 2018

Diabetes Obesity Metabolism

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AimsTo investigate the effect of kisspeptin on glucose‐stimulated insulin secretion and appetite in humans.Materials and methodsIn 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m−2), we compared the effects of 1 nmol kg−1 h−1 kisspeptin versus vehicle administration on glucose‐stimulated insulin secretion, metabolites, gut hormones, appetite and food intake. In addition, we assessed the effect of kisspeptin on glucose‐stimulated insulin secretion in vitro in human pancreatic islets and a human β‐cell line (EndoC‐βH1 cells).ResultsKisspeptin administration to healthy men enhanced insulin secretion following an intravenous glucose load, and modulated serum metabolites. In keeping with this, kisspeptin increased glucose‐stimulated insulin secretion from human islets and a human pancreatic cell line in vitro. In addition, kisspeptin administration did not alter gut hormones, appetite or food intake in healthy men.ConclusionsCollectively, these data demonstrate for the first time a beneficial role for kisspeptin in insulin secretion in humans in vivo. This has important implications for our understanding of the links between reproduction and metabolism in humans, as well as for the ongoing translational development of kisspeptin‐based therapies for reproductive and potentially metabolic conditions.

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Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose.

Cited by 1,497 publications

References 28 publications

Evidence that autonomic mechanisms contribute to the adaptive increase in insulin secretion during dexamethasone-induced insulin resistance in humans

Evidence that autonomic mechanisms contribute to the adaptive increase in insulin secretion during dexamethasone-induced insulin resistance in humans

Glucagon secretion in relation to insulin sensitivity in healthy subjects

The effects of kisspeptin on β‐cell function, serum metabolites and appetite in humans

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