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Diabetologia

, Volume 36, Issue 12, pp 1238–1244 | Cite as

Beta-cell hypersensitivity for glucose precedes loss of glucose-induced insulin secretion in 90% pancreatectomized rats

  • J. L. Leahy
  • L. M. Bumbalo
  • C. Chen
Originals

Summary

Glucose-induced insulin secretion is impaired in the presence of chronic hyperglycaemia. Insulin secretion was studied in a diabetic rat model prior to the beta cells becoming non-responsive to glucose in order to map out the sequence of changes that accompany chronic hyperglycaemia. In vitro pancreas perfusions were carried out 1 and 2 weeks after a 90% pancreatectomy; controls underwent a sham pancreatectomy. One week post 90% pancreatectomy: (i) non-fasting plasma glucose values were 2–3 mmol/l above normal, (ii) the in vitro insulin response to 16.7 mmol/l glucose was 20 ± 4% of shams, a response that was appropriate for the surgical reduction in beta-cell mass, (iii) the beta-cell sensitivity for glucose was increased as reflected by left-shifted dose-response curves for glucose-induced insulin secretion (half maximal insulin output 5.7 mmol/l glucose vs 16.5 mmol/l glucose in shams) and glucose potentiation of arginine-induced insulin secretion (half maximal insulin output 3.5 mmol/l glucose vs 14.8 mmol/l glucose in shams). This heightened beta-cell sensitivity for glucose was not a result of the hyperglycaemia, because similarly reduced half-maximal insulin responses were found after a 60% pancreatectomy, a surgical procedure in which plasma glucose values remained normal. In summary, a rise in beta-cell sensitivity for glucose precedes the loss of glucose-induced insulin secretion in diabetic rats.

Key words

Islets of Langerhans insulin secretion perfused pancreas glucose arginine partial pancreatectomy 

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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • J. L. Leahy
    • 1
    • 2
  • L. M. Bumbalo
    • 1
    • 2
  • C. Chen
    • 1
    • 2
  1. 1.Division of Endocrinology, Metabolism, and Molecular MedicineNew England Medical CenterUSA
  2. 2.Tuft's University School of MedicineBostonUSA

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