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)
Department of Internal Medicine, Istituto Scientifico San Raffaele, University of Milan, Italy.
L
L
Luzi
A
A
Battezzati
G
G
Perseghin
E
E
Bianchi
S
S
Vergani
A
A
Secchi
E
E
La Rocca
C
C
Staudacher
D
D
Spotti
G
G
Ferrari
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