Lack of feedback inhibition of insulin secretion in denervated human pancreas.
In this study, pancreas transplantation is used as a clinical model of pancreas denervation in humans. To assess the role of innervation on the feedback autoinhibition of insulin secretion, we studied four groups of subjects--group 1: 16 patients with combined pancreas and kidney transplantation (plasma glucose = 5.1 mM, HbA1c = 6.4%, creatinine = 86 mM); group 2: 8 patients with chronic uveitis on the same immunosuppressive therapy as transplanted patients (12 mg/day prednisone, 5 mg.kg-1.day-1 CsA); group 3: 4 uremic, nondiabetic patients in chronic hemodialysis; group 4: 7 normal, nondiabetic control subjects. The following means were used to study the groups: 1) a two-step hyperinsulinemic euglycemic clamp (insulin infusion rate = 1 mU and 5 mU.kg-1.min-1); and 2) a 0.3 mU.kg-1.min-1 hypoglycemic clamp (steady-state plasma glucose = 3.1 mM). Basal plasma-free IRI (84 +/- 6, 42 +/- 12, 72 +/- 12, and 30 +/- 6 pM in groups 1, 2, 3, and 4, respectively), basal C-peptide (0.79 +/- 0.05, 0.66 +/- 0.05, 3.04 +/- 0.20, and 0.59 +/- 0.06 nM in groups 1, 2, 3, and 4, respectively), and glucagon (105 +/- 13, 69 +/- 4, 171 +/- 10, and 71 +/- 5 pg/ml in groups 1, 2, 3, and 4, respectively) were increased in groups 1 and 3 with respect to groups 2 and 4 (P < 0.01). During euglycemic hyperinsulinemia, plasma C-peptide decreased by 45, 20, and 44% in groups 2, 3, and 4, respectively, but showed no significant change from the basal in patients with transplanted pancreases.(ABSTRACT TRUNCATED AT 250 WORDS)
Luzi
L
L
Department of Internal Medicine, Istituto Scientifico San Raffaele, University of Milan, Italy.
Battezzati
A
A
Perseghin
G
G
Bianchi
E
E
Vergani
S
S
Secchi
A
A
La Rocca
E
E
Staudacher
C
C
Spotti
D
D
Ferrari
G
G
D020155:3-Hydroxybutyric Acid; D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003714:Denervation; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000097:blood / Q000601:surgery; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005246:Feedback; D005500:Follow-Up Studies; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006728:Hormones / Q000097:blood*; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D016030:Kidney Transplantation / Q000502:physiology*; D007773:Lactates / Q000097:blood; D010179:Pancreas / Q000294:innervation*; D016035:Pancreas Transplantation / Q000502:physiology*; D010191:Pancreatic Polypeptide / Q000097:blood; D013004:Somatostatin / Q000097:blood; D014511:Uremia / Q000209:etiology / Q000601:surgery
D020155:3-Hydroxybutyric Acid; D001786:Blood Glucose; D002096:C-Peptide; D004837:Epinephrine; D005230:Fatty Acids, Nonesterified; D005934:Glucagon; D006442:Glycated Hemoglobin; D006728:Hormones; D006885:Hydroxybutyrates; D007328:Insulin; D007773:Lactates; D010191:Pancreatic Polypeptide; D013004:Somatostatin