Diabetes/metabolism research and reviews · 2002
Role of amylin in insulin secretion and action in humans: antagonist studies across the spectrum of insulin sensitivity.
Сравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАПоддержка правительства СШАПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Mather Kieren J, Paradisi Giancarlo, Leaming Rosalind, Hook Ginger, Steinberg Helmut O, Fineberg Naomi, Hanley Rochelle, Baron Alain D
Аннотация
BACKGROUND: Amylin is a peptide co-secreted with insulin by pancreatic beta-cells. A role for amylin in the pathogenesis of type 2 diabetes mellitus (DM2) has been suggested by in vitro and in vivo studies indicating an effect of amylin to cause insulin resistance and/or inhibit insulin secretion.
METHODS: We have determined the effect of endogenous amylin on insulin secretion and insulin action in humans by performing 4-h hyperglycemic clamps during infusion of placebo or a specific amylin receptor antagonist (ARA) in paired, double-blinded, crossover studies. We studied nine healthy lean, ten healthy obese (BMI>27) and ten obesity-matched DM2 subjects.
RESULTS: Infusion of ARA alone had no effect on basal insulin, glucose or glucose turnover in any group. Under combined hyperglycemia and ARA infusion, lean subjects displayed a 32% augmentation in insulin levels [AUC 33,565+/-3556 (placebo) to 44,562+/-1379 (ARA) pmol/l/min, p<0.01]. The concomitant increase in glucose disposal rate (GDR) was proportionate, indicating no change in insulin sensitivity (ISI 27.7+/-2.7 vs 27.3+/-2.1, p=NS). In obese subjects, basal insulin and the rise in insulin during the clamp were greater (AUC I 44% increase from 82,054+/-15 407 to 117,922+/-27,085, p<0.01), and also accompanied by a proportionate rise in GDR reflecting an unchanged insulin sensitivity (ISI 12.1+/-2.9 vs 10.8+/-3.0, p=NS). In lean and obese subjects, the C-peptide response to hyperglycemia was also augmented by ARA (p=0.007). No effect of ARA on insulin secretion or action was observed in diabetic subjects.
CONCLUSIONS: The present data are consistent with an effect of endogenous amylin on the beta-cell to modulate and/or restrain insulin secretion, and indicate that endogenous amylin does not affect insulin action. These observations provide the first human evidence that amylin plays a role in the modulation of insulin secretion.
METHODS: We have determined the effect of endogenous amylin on insulin secretion and insulin action in humans by performing 4-h hyperglycemic clamps during infusion of placebo or a specific amylin receptor antagonist (ARA) in paired, double-blinded, crossover studies. We studied nine healthy lean, ten healthy obese (BMI>27) and ten obesity-matched DM2 subjects.
RESULTS: Infusion of ARA alone had no effect on basal insulin, glucose or glucose turnover in any group. Under combined hyperglycemia and ARA infusion, lean subjects displayed a 32% augmentation in insulin levels [AUC 33,565+/-3556 (placebo) to 44,562+/-1379 (ARA) pmol/l/min, p<0.01]. The concomitant increase in glucose disposal rate (GDR) was proportionate, indicating no change in insulin sensitivity (ISI 27.7+/-2.7 vs 27.3+/-2.1, p=NS). In obese subjects, basal insulin and the rise in insulin during the clamp were greater (AUC I 44% increase from 82,054+/-15 407 to 117,922+/-27,085, p<0.01), and also accompanied by a proportionate rise in GDR reflecting an unchanged insulin sensitivity (ISI 12.1+/-2.9 vs 10.8+/-3.0, p=NS). In lean and obese subjects, the C-peptide response to hyperglycemia was also augmented by ARA (p=0.007). No effect of ARA on insulin secretion or action was observed in diabetic subjects.
CONCLUSIONS: The present data are consistent with an effect of endogenous amylin on the beta-cell to modulate and/or restrain insulin secretion, and indicate that endogenous amylin does not affect insulin action. These observations provide the first human evidence that amylin plays a role in the modulation of insulin secretion.