Lack of feedback inhibition of insulin secretion in denervated human pancreas

L. Luzi, A. Battezzati, G. Perseghin, E. Bianchi, S. Vergani, A. Secchi, E. La Rocca, C. Staudacher, D. Spotti, G. Ferrari, V. Di Carlo, G. Pozza

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Abstract

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, HbA(1c) = 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. During insulin-induced hypoglycemia, C-peptide concentration was suppressed by 80 and 85% in groups 2 and 4, respectively, but only by 57 and 40% in groups 1 and 3, respectively; glucagon response was blunted in patients with transplanted pancreases in all groups. In conclusion, these results support the hypothesis that feedback inhibition of insulin secretion is mediated by neural control in humans. The partial restoration of inhibition of insulin secretion during hypoglycemia presumably is attributable to catecholamine release, or to exposure of the β-cell to low glucose concentration.

Original languageEnglish
Pages (from-to)1632-1639
Number of pages8
JournalDiabetes
Volume41
Issue number12
Publication statusPublished - 1992

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Luzi, L., Battezzati, A., Perseghin, G., Bianchi, E., Vergani, S., Secchi, A., La Rocca, E., Staudacher, C., Spotti, D., Ferrari, G., Di Carlo, V., & Pozza, G. (1992). Lack of feedback inhibition of insulin secretion in denervated human pancreas. Diabetes, 41(12), 1632-1639.