title: Insulin infusion during normoglycemia modulates insulin secretion according to whole-body insulin sensitivity.
abstract: OBJECTIVE
  Glucose is the major stimulus for insulin release. Time course and amount of insulin secreted after glycemic stimulus are different between type 2 diabetes mellitus (T2DM) patients and healthy subjects. In rodents, it was demonstrated that insulin can modulate its own release. Previous studies in humans yielded contrasting results: Insulin was shown to have an enhancing effect, no effect, or a suppressive effect on its own secretion. Thus, we aimed to evaluate short-term effects of human insulin infusion on insulin secretion during normoglycemia in healthy humans and T2DM subjects of both sex.
  
  
  METHODS
  Hyperinsulinemic-isoglycemic clamps with whole-body insulin-sensitivity (M) and C-peptide measurements for insulin secretion modeling were performed in 65 insulin-sensitive (IS) subjects (45 ± 1 year, BMI: 24.8 ± 0.5 kg/m(2)), 17 insulin-resistant (IR) subjects (46 ± 2 years, 28.1 ± 1.3 kg/m(2)), and 20 T2DM patients (56 ± 2 years, 28.0 ± 0.8 kg/m(2); HbA(1c) = 6.7 ± 0.1%).
  
  
  RESULTS
  IS subjects (M = 8.8 ± 0.3 mg · min(-1) · kg(-1)) had higher (P < 0.00001) whole-body insulin sensitivity than IR subjects (M = 4.0 ± 0.2) and T2DM patients (M = 4.3 ± 0.5). Insulin secretion profiles during clamp were different (P < 0.00001) among the groups, increasing in IS subjects (slope: 0.56 ± 0.11 pmol/min(2)) but declining in IR (-0.41 ± 0.14) and T2DM (-0.87 ± 0.12, P < 0.00002 IR and T2DM vs. IS) subjects. Insulin secretion changes during clamp directly correlated with M (r = 0.6, P < 0.00001).
  
  
  CONCLUSIONS
  Insulin release during normoglycemia can be modulated by exogenous insulin infusion and directly depends on whole-body insulin sensitivity. Thus, in highly sensitive subjects, insulin increases its own secretion. On the other hand, a suppressive effect of insulin on its own secretion occurs in IR and T2DM subjects.
authors.affiliation: Metabolic Unit, Institute of Biomedical Engineering, National Research Council, Padova, Italy. christian-heinz.anderwald@meduniwien.ac.at
authors.forename: Christian
authors.initials: C
authors.lastname: Anderwald
authors.forename: Andrea
authors.initials: A
authors.lastname: Tura
authors.forename: Angela
authors.initials: A
authors.lastname: Grassi
authors.forename: Michael
authors.initials: M
authors.lastname: Krebs
authors.forename: Julia
authors.initials: J
authors.lastname: Szendroedi
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.forename: Martin G
authors.initials: MG
authors.lastname: Bischof
authors.forename: Anton
authors.initials: A
authors.lastname: Luger
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin