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Pulsatile insulin delivery is more efficient than continuous infusion in modulating islet cell function in normal subjects and patients with type 1 diabetes.
J Clin Endocrinol Metab. 1988 Jun; 66(6):1220-6.JC

Abstract

The respective modulating effects of continuous and intermittent insulin delivery on pancreatic islet cell function were studied in seven normal men and nine insulin-dependent (type 1) diabetic patients. In the normal men, saline or continuous (0.8 mU kg-1 min-1) or pulsatile (5.2 mU kg-1 min-1, with a switching on/off length of 2/11 min) human insulin were delivered on different days and in random order. Despite hyperinsulinemia, blood glucose was kept close to its basal value by the glucose clamp technique. The diabetic patients also were infused in random order and on different days with either saline or a smaller amount of insulin delivered continuously (0.15 mU kg-1 min-1) or in a pulsatile manner (0.97 mU kg-1 min-1 for 2 min, followed by 11 min during which no insulin was infused). In all experiments, 5 g arginine were given iv as a bolus dose 30 min before the end of the study, and plasma C-peptide and glucagon levels were determined to assess islet cell function. In the normal men, insulin administration resulted in a significant decline of basal plasma glucagon and C-peptide levels and in a clear-cut decrease in the arginine-induced glucagon response. These effects of insulin were significantly more marked when insulin was delivered in a pulsatile rather than a continuous manner. In the insulin-dependent diabetic patients, the lower dose of insulin infused continuously did not alter the basal or arginine-stimulated glucagon response. In contrast, when the same amount of insulin was delivered intermittently, arginine-induced glucagon release was greatly reduced. Thus, these data support the concept that insulin per se is a potent physiological modulator of islet A- and B-cell function. Furthermore, they suggest that these effects of insulin are reinforced when the hormone is administered in an intermittent manner in an attempt to reproduce the pulsatile physiological release of insulin.

Authors+Show Affiliations

Istituto di Clinica Medica, First Medical School, University of Naples, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

3286673

Citation

Paolisso, G, et al. "Pulsatile Insulin Delivery Is More Efficient Than Continuous Infusion in Modulating Islet Cell Function in Normal Subjects and Patients With Type 1 Diabetes." The Journal of Clinical Endocrinology and Metabolism, vol. 66, no. 6, 1988, pp. 1220-6.
Paolisso G, Sgambato S, Torella R, et al. Pulsatile insulin delivery is more efficient than continuous infusion in modulating islet cell function in normal subjects and patients with type 1 diabetes. J Clin Endocrinol Metab. 1988;66(6):1220-6.
Paolisso, G., Sgambato, S., Torella, R., Varricchio, M., Scheen, A., D'Onofrio, F., & Lefèbvre, P. J. (1988). Pulsatile insulin delivery is more efficient than continuous infusion in modulating islet cell function in normal subjects and patients with type 1 diabetes. The Journal of Clinical Endocrinology and Metabolism, 66(6), 1220-6.
Paolisso G, et al. Pulsatile Insulin Delivery Is More Efficient Than Continuous Infusion in Modulating Islet Cell Function in Normal Subjects and Patients With Type 1 Diabetes. J Clin Endocrinol Metab. 1988;66(6):1220-6. PubMed PMID: 3286673.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pulsatile insulin delivery is more efficient than continuous infusion in modulating islet cell function in normal subjects and patients with type 1 diabetes. AU - Paolisso,G, AU - Sgambato,S, AU - Torella,R, AU - Varricchio,M, AU - Scheen,A, AU - D'Onofrio,F, AU - Lefèbvre,P J, PY - 1988/6/1/pubmed PY - 1988/6/1/medline PY - 1988/6/1/entrez SP - 1220 EP - 6 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 66 IS - 6 N2 - The respective modulating effects of continuous and intermittent insulin delivery on pancreatic islet cell function were studied in seven normal men and nine insulin-dependent (type 1) diabetic patients. In the normal men, saline or continuous (0.8 mU kg-1 min-1) or pulsatile (5.2 mU kg-1 min-1, with a switching on/off length of 2/11 min) human insulin were delivered on different days and in random order. Despite hyperinsulinemia, blood glucose was kept close to its basal value by the glucose clamp technique. The diabetic patients also were infused in random order and on different days with either saline or a smaller amount of insulin delivered continuously (0.15 mU kg-1 min-1) or in a pulsatile manner (0.97 mU kg-1 min-1 for 2 min, followed by 11 min during which no insulin was infused). In all experiments, 5 g arginine were given iv as a bolus dose 30 min before the end of the study, and plasma C-peptide and glucagon levels were determined to assess islet cell function. In the normal men, insulin administration resulted in a significant decline of basal plasma glucagon and C-peptide levels and in a clear-cut decrease in the arginine-induced glucagon response. These effects of insulin were significantly more marked when insulin was delivered in a pulsatile rather than a continuous manner. In the insulin-dependent diabetic patients, the lower dose of insulin infused continuously did not alter the basal or arginine-stimulated glucagon response. In contrast, when the same amount of insulin was delivered intermittently, arginine-induced glucagon release was greatly reduced. Thus, these data support the concept that insulin per se is a potent physiological modulator of islet A- and B-cell function. Furthermore, they suggest that these effects of insulin are reinforced when the hormone is administered in an intermittent manner in an attempt to reproduce the pulsatile physiological release of insulin. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/3286673/Pulsatile_insulin_delivery_is_more_efficient_than_continuous_infusion_in_modulating_islet_cell_function_in_normal_subjects_and_patients_with_type_1_diabetes_ DB - PRIME DP - Unbound Medicine ER -