title: Increased action of pulsatile compared to non-pulsatile insulin delivery during a meal-like glucose exposure simulated by computerized infusion in healthy humans.
abstract: It has previously been demonstrated that pulsatile insulin has a greater hypoglycemic effect than non-pulsatile insulin during euglycemic conditions. The aim of the present study was to examine the effect of pulsatile versus non-pulsatile insulin delivery during a meal-like iv-glucose challenge. Ten healthy young subjects were examined on two occasions. A pancreatic-pituitary clamp was maintained with somatostatin infusion and replacement of glucagon and growth hormone at baseline levels. During the first three hours on both study days, insulin was infused in a pulsatile manner. Hereafter glucose and insulin were infused by computer-controlled pumps for four hours in a pattern mimicking the postprandial glucose and insulin profiles. At one study day, insulin infusion was done in a continuous manner, while at the other study day this profile was done in a pulsatile pattern. The hypoglycemic effect of insulin was measured as the integrated area under the curve of glucose during the four-hour infusion period. The mean insulin concentration measured as the integrated area under the curve was identical (P > .9). The hypoglycemic effect of insulin was significantly augmented by 13% during pulsatile delivery as compared to continuous delivery (P = .015). Likewise was the maximal glucose concentration significantly lower at the day of the pulsatile profile (9.9 ± 1.0 vs. 11.4 ± 2.3 mmol/l, P = .036). Pulsatile insulin release plays an important role in the postprandial glucose homeostasis. The disturbed insulin pulsatility in type 2 diabetes mellitus may contribute to the postprandial hyperglycemia.
authors.affiliation: Medical Department, Esbjerg Hospital, Denmark; Medical Department M, Aarhus University Hospital, Denmark. claus.juhl@dadlnet.dk
authors.forename: Claus B
authors.initials: CB
authors.lastname: Juhl
authors.forename: Jacob
authors.initials: J
authors.lastname: Gjedsted
authors.forename: Michael F
authors.initials: MF
authors.lastname: Nielsen
authors.forename: Ole
authors.initials: O
authors.lastname: Schmitz
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D003198:Computer Simulation; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004435:Eating; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood; D054795:Incretins / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D007332:Insulin Infusion Systems; D000078790:Insulin Secretion; D008297:Male; D010187:Pancreatic Hormones / Q000378:metabolism; D010907:Pituitary Hormones / Q000378:metabolism; D019518:Postprandial Period; D011673:Pulsatile Flow; D012107:Research Design; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D010187:Pancreatic Hormones; D010907:Pituitary Hormones; D019382:Human Growth Hormone; D005934:Glucagon