Diurnal Variation in Glucose Tolerance: Cyclic Suppression of Insulin Action and Insulin Secretion in Normal-Weight, But Not Obese, Subjects

The study investigated whether a persistent impairment of insulin secretion resulting from mild protein restriction predisposes to loss of glucoregulatory control and impaired insulin action after the subsequent imposition of the diabetogenic challenge of high-fat feeding. Offspring of dams provided with either control (20% protein) diet (C) or an isocaloric restricted (8%) protein diet (PR) were weaned onto the maintenance diet with which their mothers had been provided. At 20 wk of age, protein restriction enhanced glucose tolerance despite impaired insulin secretion and an augmented and sensitized lipolytic response to norepinephrine in adipocytes. C and PR rats were then transferred to a high-fat diet (HF, 19% protein, 22% lipid, 34% carbohydrate) and sampled after 8 wk. These groups are termed C-HF and PR-HF. Glucose tolerance was impaired in PR-HF, but not C-HF, rats. Insulin-stimulated glucose disposal rates were significantly lower (by 30%; P < 0.01) in the PR-HF group than in the C-HF group, and a specific impairment of antilipolytic response of insulin was unmasked in adipocytes from PR-HF, but not C-HF, rats. The study demonstrates that antecedent protein restriction accelerates and augments the development of impaired glucoregulation and insulin resistance after high-fat feeding.

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Effect of early dietary restriction on insulin action and secretion in the GK rat, a spontaneous model of NIDDM

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2000.278.6.e1097 ◽

2000 ◽

Vol 278 (6) ◽

pp. E1097-E1103 ◽

Cited By ~ 3

Author(s):

Carmen Alvarez ◽

Danielle Bailbe ◽

Françoise Picarel-Blanchot ◽

Eric Bertin ◽

Ana-Maria Pascual-Leone ◽

...

Keyword(s):

Insulin Secretion ◽

Weight Gain ◽

Glucose Tolerance ◽

Glucose Uptake ◽

Insulin Action ◽

Food Restriction ◽

Plasma Insulin ◽

Insulin Level ◽

Gk Rat ◽

Basal Plasma

The availability of the Goto-Kakisaki (GK) rat model of non-insulin-dependent diabetes mellitus prompted us to test the effect of a limited period of undernutrition in previously diabetic young rats on their insulin secretion and insulin action during adult age. Four-week-old female GK rats were either food restricted (35% restriction, 15% protein diet) or protein and energy restricted (35% restriction, 5% protein diet) for 4 wk. Food restriction in the young GK rat lowered weight gain but did not aggravate basal hyperglycemia or glucose intolerance, despite a decrease in basal plasma insulin level. Furthermore, the insulin-mediated glucose uptake by peripheral tissues in the GK rat was clearly improved. We also found that food restriction, when it is coupled to overt protein deficiency in the young GK rat, altered weight gain more severely and slightly decreased basal hyperglycemia but conversely aggravated glucose tolerance. Improvement of basal hyperglycemia was related to repression of basal hepatic glucose hyperproduction, despite profound attenuation of basal plasma insulin level. Deterioration of tolerance to glucose was related to severe blunting of the residual glucose-induced insulin secretion. It is, however, likely that the important enhancement of the insulin-mediated glucose uptake helped to limit the deterioration of glucose tolerance.

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1-Hour OGTT Plasma Glucose as a Marker of Progressive Deterioration of Insulin Secretion and Action in Pregnant Women

International Journal of Endocrinology ◽

10.1155/2012/460509 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Alessandra Ghio ◽

Giuseppe Seghieri ◽

Cristina Lencioni ◽

Roberto Anichini ◽

Alessandra Bertolotto ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Pregnant Women ◽

Plasma Glucose ◽

Glucose Concentration ◽

Insulin Action ◽

Progressive Increase ◽

Plasma Glucose Concentration ◽

Linear Manner

Considering old GDM diagnostic criteria, alterations in insulin secretion and action are present in women with GDM as well as in women with one abnormal value (OAV) during OGTT. Our aim is to assess if changes in insulin action and secretion during pregnancy are related to 1-hour plasma glucose concentration during OGTT. We evaluated 3 h/100 g OGTT in 4,053 pregnant women, dividing our population on the basis of 20 mg/dL increment of plasma glucose concentration at 1 h OGTT generating 5 groups (<120 mg/dL,n=661; 120–139 mg/dL,n=710; 140–159 mg/dL,n=912; 160–179 mg/dL,n=885; and ≥180 mg/dL,n=996). We calculated incremental area under glucose (AUCgluc) and insulin curves (AUCins), indexes of insulin secretion (HOMA-B), and insulin sensitivity (HOMA-R), AUCins/AUCgluc. AUCglucand AUCinsprogressively increased according to 1-hour plasma glucose concentrations (bothP<0.0001for trend). HOMA-B progressively declined (P<0.001), and HOMA-R progressively increased across the five groups. AUCins/AUCglucdecreased in a linear manner across the 5 groups (P<0.001). Analysing the groups with 1-hour value <180 mg/dL, defects in insulin secretion (HOMA-B: −29.7%) and sensitivity (HOMA-R: +15%) indexes were still apparent (allP<0.001). Progressive increase in 1-hour OGTT is associated with deterioration of glucose tolerance and alterations in indexes of insulin action and secretion.

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Diurnal Variation in Glucose Tolerance and in Insulin Secretion in Man

Diabetes ◽

10.2337/diab.22.5.333 ◽

1973 ◽

Vol 22 (5) ◽

pp. 333-348 ◽

Cited By ~ 144

Author(s):

K. F. Carroll ◽

P. J. Nestel

Keyword(s):

Insulin Secretion ◽

Glucose Tolerance ◽

Diurnal Variation

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Influence of Physical Training on Blood Glucose Control, Glucose Tolerance, Insulin Secretion, and Insulin Action in Non-insulin-dependent Diabetic Patients

Diabetes Care ◽

10.2337/diacare.7.5.416 ◽

1984 ◽

Vol 7 (5) ◽

pp. 416-420 ◽

Cited By ~ 114

Author(s):

M. Trovati ◽

Q. Carta ◽

F. Cavalot ◽

S. Vitali ◽

C. Banaudi ◽

...

Keyword(s):

Insulin Secretion ◽

Blood Glucose ◽

Glucose Tolerance ◽

Physical Training ◽

Glucose Control ◽

Insulin Action ◽

Blood Glucose Control ◽

Diabetic Patients ◽

Insulin Dependent ◽

Insulin Dependent Diabetic

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Salicylates Increase Insulin Secretion in Healthy Obese Subjects

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-1212 ◽

2008 ◽

Vol 93 (7) ◽

pp. 2523-2530 ◽

Cited By ~ 21

Author(s):

José-Manuel Fernández-Real ◽

Abel López-Bermejo ◽

Ana-Belén Ropero ◽

Sandra Piquer ◽

Angel Nadal ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Treatment Period ◽

Islets Of Langerhans ◽

Glucose Concentration ◽

Human Islets ◽

Serum Glucose ◽

Obese Subjects ◽

Healthy Obese

Abstract Context: Conflicting results on the effects of salicylates on glucose tolerance in subjects with normal glucose tolerance or type 2 diabetes have been reported. Objective: The objective of the study was to investigate the effects of a salicylate derivative (triflusal) on insulin sensitivity and insulin secretion. Design, Setting, and Participants: This was a double-blind, randomized, crossover study with three treatment periods corresponding to two dose levels of triflusal and placebo in healthy obese subjects. Main Outcome Measures: Insulin sensitivity and insulin secretion, evaluated through frequently sampled iv glucose tolerance test that was performed after each treatment period, were measured. Insulin secretion was also evaluated in vitro in mice and human islets of Langerhans. Results: The administration of triflusal led to decreased fasting serum glucose concentration in the study subjects. Insulin sensitivity did not significantly change after each treatment period. Insulin secretion, however, significantly increased in a dose-dependent fashion after each triflusal treatment period. The administration of 800 μm of the main triflusal metabolite to whole mice islets of Langerhans led to a sustained increase in intracellular calcium concentration level. This was followed by a significantly increase in insulin secretion. In human islets, 200 μm of 2-hydroxy-4-trifluoromethylbenzoic acid was sufficient to increase insulin release. Conclusions: The administration of a salicylate compound led to lowering of serum glucose concentration. We suggest that this effect was mediated through increased insulin secretion induced by salicylate directly on the β-cell.

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The incretin effect in obese adolescents with and without type 2 diabetes: impaired or intact?

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00496.2015 ◽

2016 ◽

Vol 310 (9) ◽

pp. E774-E781 ◽

Cited By ~ 6

Author(s):

Benedikt A. Aulinger ◽

Torsten P. Vahl ◽

Ron L. Prigeon ◽

David A. D'Alessio ◽

Deborah A. Elder

Keyword(s):

Insulin Secretion ◽

Glucose Tolerance ◽

Cell Function ◽

Insulin Response ◽

Incretin Effect ◽

Β Cell ◽

Early Marker ◽

Obesity And Diabetes ◽

Obese Subjects ◽

Young Subjects

The incretin effect reflects the actions of enteral stimuli to promote prandial insulin secretion. Impairment of this measure has been proposed as an early marker of β-cell dysfunction and described in T2D, IGT, and even obesity without IGT. We sought to determine the effects of obesity and diabetes on the incretin effect in young subjects with short exposures to metabolic abnormalities and a few other confounding medical conditions. Subjects with T2D ( n = 10; 18.0 ± 0.4 yr) or NGT, either obese ( n = 11; 17.7 ± 0.4 yr) or lean ( n = 8; 26.5 ± 2.3 yr), had OGTT and iso-iv. The incretin effect was calculated as the difference in insulin secretion during these tests and was decreased ∼50% in both the NGT-Ob and T2D subjects relative to the NGT-Ln group. The T2D group had impaired glucose tolerance and insulin secretion during the OGTT, whereas the lean and obese NGT subjects had comparable glucose excursions and β-cell function. During the iso-iv test, the NGT-Ob subjects had significantly greater insulin secretion than the NGT-Ln and T2D groups. These findings demonstrate that in young subjects with early, well-controlled T2D the incretin effect is reduced, similar to what has been described in diabetic adults. The lower incretin effect calculated for the obese subjects with NGT is driven by a disproportionately greater insulin response to iv glucose and does not affect postprandial glucose regulation. These findings confirm that the incretin effect is an early marker of impaired insulin secretion in persons with abnormal glucose tolerance but suggest that in obese subjects with NGT the incretin effect calculation can be confounded by exaggerated insulin secretion to iv glucose.

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