Glucagon sensitivity and clearance in type 1 diabetes: Insights from in vivo and in silico experiments

Ling Hinshaw, Ashwini Mallad, Chiara Dalla Man, Rita Basu, Claudio Cobelli, Rickey E. Carter, Yogish C Kudva, Ananda Basu

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Glucagon use in artificial pancreas for type 1 diabetes (T1D) is being explored for prevention and rescue from hypoglycemia. However, the relationship between glucagon stimulation of endogenous glucose production (EGP) viz., hepatic glucagon sensitivity, and prevailing glucose concentrations has not been examined. To test the hypothesis that glucagon sensitivity is increased at hypoglycemia vs. euglycemia, we studied 29 subjects with T1D randomized to a hypoglycemia or euglycemia clamp. Each subject was studied at three glucagon doses at euglycemia or hypoglycemia, with EGP measured by isotope dilution technique. The peak EGP increments and the integrated EGP response increased with increasing glucagon dose during euglycemia and hypoglycemia. However, the difference in dose response based on glycemia was not significant despite higher catecholamine concentrations in the hypoglycemia group. Knowledge of glucagon’s effects on EGP was used to develop an in silico glucagon action model. The model-derived output fitted the obtained data at both euglycemia and hypoglycemia for all glucagon doses tested. Glucagon clearance did not differ between glucagon doses studied in both groups. Therefore, the glucagon controller of a dual hormone control system may not need to adjust glucagon sensitivity, and hence glucagon dosing, based on glucose concentrations during euglycemia and hypoglycemia.

Original languageEnglish (US)
Pages (from-to)E474-E486
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume309
Issue number5
DOIs
StatePublished - Sep 4 2015

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Keywords

  • Endogenous glucose production
  • Glucagon
  • Type 1 diabetes

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

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